Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Improving Oral Absorption Via Drug-loaded Nanocarriers: Absorption Mechanisms, Intestinal Models And Rational Fabrication.

M. Shahbazi, H. Santos
Published 2013 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Although it is acknowledged that the main impediment of orally administered therapeutic agents is their extensive and changeable pre-systemic metabolism, low absorption and instability in harsh environment of the gastrointestinal (GI) tract are also main influential factors, resulting into inadequate and erratic drug bioavailability. To overcome these shortcomings, nanotechnology has offered new promising strategies to prevent and treat a wide variety of diseases by employing different oral drug-carrier structures capable to enhance therapeutic effects and minimize the toxicity of healthy organs or cells. This review, in general, elucidates some considerable features of in vitro oral drug delivery in three different parts. The first one summarizes the main challenges for oral drug delivery and available absorption mechanisms. The second part embodies an in-depth discussion on the role of the intestinal absorption models used to predict permeability, cellular uptake or even toxicity of nanoparticles, resulting into the design of nanocarriers with optimum efficacy for oral delivery. The third section of the literature is devoted, more particularly, to nanocarriers developed for oral absorption in the past few years, including the behavior of nanovehicles upon oral administration with respect to membrane permeability, retention properties and stability, as well as methods which may lengthen residence time in the GI environment or improve drug absorption.
This paper references
10.1016/S0168-3659(02)00072-X
Behavior of mucoadhesive nanoparticles having hydrophilic polymeric chains in the intestine.
Shinji Sakuma (2002)
10.1208/s12249-010-9390-3
Insulin-Loaded Nanoparticles Based on N-Trimethyl Chitosan: In Vitro (Caco-2 Model) and Ex Vivo (Excised Rat Jejunum, Duodenum, and Ileum) Evaluation of Penetration Enhancement Properties
G. Sandri (2010)
10.1074/jbc.M503202200
High Density of Octaarginine Stimulates Macropinocytosis Leading to Efficient Intracellular Trafficking for Gene Expression*
I. Khalil (2006)
10.1023/A:1022643802296
An Improved Cell Culture Model Based on 2/4/A1 Cell Monolayers for Studies of Intestinal Drug Transport: Characterization of Transport Routes
S. Tavelin (2004)
10.1002/jps.22570
Structural Features Determining the Intestinal Epithelial Permeability and Efflux of Novel HIV-1 Protease Inhibitors
L. Lazorova (2011)
10.1016/j.ijpharm.2009.11.005
Intracellular fate of octaarginine-modified liposomes in polarized MDCK cells.
T. Fujiwara (2010)
10.1016/j.addr.2011.12.009
Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers.
Laura M Ensign (2012)
10.1016/j.addr.2009.03.005
In vitro assessments of nanomaterial toxicity.
Clinton F Jones (2009)
10.1016/J.PRRV.2007.02.009
Mucolytics in cystic fibrosis.
M. Henke (2007)
10.1023/A:1007587523543
Anionic PAMAM Dendrimers Rapidly Cross Adult Rat Intestine In Vitro: A Potential Oral Delivery System?
R. Wiwattanapatapee (2004)
10.1016/J.EJPB.2007.07.006
Cyclosporine-loaded solid lipid nanoparticles (SLN): drug-lipid physicochemical interactions and characterization of drug incorporation.
R. Mueller (2008)
10.1021/jm800767c
Conjugated chitosan as a novel platform for oral delivery of paclitaxel.
E. Lee (2008)
10.1002/anie.200802585
Nanomedicine--challenge and perspectives.
K. Riehemann (2009)
10.1016/j.jconrel.2010.10.013
Nanoemulsion improves the oral absorption of candesartan cilexetil in rats: Performance and mechanism.
F. Gao (2011)
10.1016/J.IJPHARM.2007.10.007
PLGA/PEG-derivative polymeric matrix for drug delivery system applications: Characterization and cell viability studies.
A. Fernández-Carballido (2008)
10.1016/j.ijpharm.2009.08.035
Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of Zedoary essential oil: formulation and bioavailability studies.
Y. Zhao (2010)
10.1016/j.biomaterials.2009.11.020
The utilization of pathogen-like cellular trafficking by single chain block copolymer.
G. Sahay (2010)
10.1016/S0378-5173(01)00698-6
Permeability of lipophilic compounds in drug discovery using in-vitro human absorption model, Caco-2.
G. Krishna (2001)
10.1016/J.IJPHARM.2004.10.003
Oral and subcutaneous absorption of insulin poly(isobutylcyanoacrylate) nanoparticles.
M. S. Mesiha (2005)
10.1016/j.etap.2003.11.008
Comparison of Caco-2, IEC-18 and HCEC cell lines as a model for intestinal absorption of genistein, daidzein and their glycosides.
A. Steensma (2004)
10.1016/j.surg.2009.05.007
Targeting the gut barrier: identification of a homing peptide sequence for delivery into the injured intestinal epithelial cell.
T. Costantini (2009)
10.1016/S0169-409X(98)00037-4
The effect of physical barriers and properties on the oral absorption of particulates.
Norris (1998)
10.1021/bm800913r
Block Copolymer Micelles as Nanocontainers for Controlled Release of Proteins from Biocompatible Oil Phases
A. Miller (2009)
10.1023/A:1018967116988
Effect of Chitosan on the Permeability of Monolayers of Intestinal Epithelial Cells (Caco-2)
P. Artursson (2004)
10.1007/s10856-008-3496-0
Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery
Piyali Basak (2009)
10.1016/J.JCONREL.2007.03.006
Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS).
M. Bhavsar (2007)
10.1163/156856208X393464
Molecular Aspects of Mucoadhesive Carrier Development for Drug Delivery and Improved Absorption
N. Peppas (2009)
10.1007/s12272-011-0709-8
Self-microemulsifying drug delivery system for improved oral bioavailability of dipyridamole: Preparation and evaluation
F. Guo (2011)
10.1016/J.JCONREL.2005.11.005
Influence of vitamin E TPGS poly(ethylene glycol) chain length on apical efflux transporters in Caco-2 cell monolayers.
E. Collnot (2006)
10.1016/S0928-0987(03)00146-5
Do cell culture conditions influence the carrier-mediated transport of peptides in Caco-2 cell monolayers?
I. Behrens (2003)
10.1016/J.BIOMATERIALS.2004.07.050
Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs.
K. Y. Win (2005)
10.1016/J.EJPS.2006.12.006
An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells.
A. des Rieux (2007)
10.1016/j.ejps.2009.09.010
Combined hydroxypropyl-beta-cyclodextrin and poly(anhydride) nanoparticles improve the oral permeability of paclitaxel.
M. Agüeros (2009)
10.1023/A:1016192413308
Are MDCK Cells Transfected with the Human MRP2 Gene a Good Model of the Human Intestinal Mucosa?
F. Tang (2004)
10.1023/A:1018905109971
A Drug Absorption Model Based on the Mucus Layer Producing Human Intestinal Goblet Cell Line HT29-H
A. Wikman (2004)
10.1177/1087057104267162
Comparison of in Vitro Models for the Prediction of Compound Absorption across the Human Intestinal Mucosa
S. Miret (2004)
10.1615/CRITREVTHERDRUGCARRIERSYST.V28.I2.10
Nanostructured materials in drug and gene delivery: a review of the state of the art.
Kailash C. Petkar (2011)
10.1016/S0378-5173(00)00382-3
Extrusion-spheronization of pH-sensitive polymeric matrix pellets for possible colonic drug delivery.
K. Krogars (2000)
10.1016/S0300-9084(86)80177-8
The human colon carcinoma cell lines HT-29 and Caco-2: two in vitro models for the study of intestinal differentiation.
M. Rousset (1986)
10.1016/j.taap.2011.11.010
Nanotoxicology and in vitro studies: the need of the hour.
Sumit Arora (2012)
10.1016/J.JPBA.2003.11.016
HPLC with programmed wavelength fluorescence detection for the simultaneous determination of marker compounds of integrity and P-gp functionality in the Caco-2 intestinal absorption model.
P. Augustijns (2004)
10.1016/S0168-3659(02)00087-1
Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers.
M. Elsayed (2002)
10.1021/BC025524Y
Cellular Internalization of Poly(ethylene oxide)-b-poly(ε-caprolactone) Diblock Copolymer Micelles
L. Luo (2002)
10.1016/J.EJPS.2006.04.012
Lipid composition effect on permeability across PAMPA.
Paul R. Seo (2006)
10.1016/J.VACCINE.2007.09.044
Bioadhesive capacity and immunoadjuvant properties of thiamine-coated nanoparticles.
Hesham H. Salman (2007)
10.1016/J.TIBTECH.2005.11.006
Polymer conjugates: nanosized medicines for treating cancer.
M. Vicent (2006)
10.1016/j.jconrel.2011.12.018
Monitoring the transport of polymeric micelles across MDCK cell monolayer and exploring related mechanisms.
Shanshan Zhao (2012)
10.1016/J.JPBA.2005.03.043
A novel high-throughput automated chip-based nanoelectrospray tandem mass spectrometric method for PAMPA sample analysis.
P. Balimane (2005)
10.1016/J.JCONREL.2007.02.004
PLGA nanoparticles for oral delivery of cyclosporine: nephrotoxicity and pharmacokinetic studies in comparison to Sandimmune Neoral.
J. L. Italia (2007)
10.1016/J.YMETH.2005.09.009
Lectins and microparticles for enhanced oral vaccination.
E. Lavelle (2006)
10.1023/A:1020456632737
Characterization of the Transport of Uracil Across Caco-2 and LLC-PK1 Cell Monolayers
H. Li (2004)
10.1016/S0169-409X(01)00231-9
Oral drug absorption enhancement by chitosan and its derivatives.
M. Thanou (2001)
10.1016/j.vascn.2010.02.004
Defining conditions for the co-culture of Caco-2 and HT29-MTX cells using Taguchi design.
X. Chen (2010)
10.1002/jcp.20085
Chloride channels in the small intestinal cell line IEC‐18
S. Basavappa (2005)
10.2217/nnm.10.126
Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances.
A. Date (2010)
10.1002/(SICI)1097-4636(199601)30:1<53::AID-JBM8>3.0.CO;2-Q
Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers.
J. Roberts (1996)
10.1016/J.IJPHARM.2005.10.033
Synthesis, characterization and stability of dendrimer prodrugs.
Mohammad Najlah (2006)
Effect of molecular charge on intestinal epithelial drug transport: pH-dependent transport of cationic drugs.
K. Palm (1999)
10.1038/nrd1088
The dawning era of polymer therapeutics
R. Duncan (2003)
10.1016/J.IJPHARM.2006.11.047
In vitro evaluation of dendrimer prodrugs for oral drug delivery.
M. Najlah (2007)
10.1016/j.addr.2008.11.002
Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.
S. Lai (2009)
10.1111/j.2042-7158.1989.tb06377.x
The Uptake and Translocation of Latex Nanospheres and Microspheres after Oral Administration to Rats
P. Jani (1989)
10.1016/J.BIOMATERIALS.2005.03.021
Poly(d,l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs.
Yuancai Dong (2005)
10.1016/S1359-6446(03)02873-3
In vitro trans-monolayer permeability calculations: often forgotten assumptions.
K. Youdim (2003)
10.1007/s10439-005-8973-8
Oral Chemotherapeutic Delivery: Design and Cellular Response
J. Blanchette (2005)
10.1016/J.ADDR.2003.10.036
Apical membrane receptors on intestinal M cells: potential targets for vaccine delivery.
D. Brayden (2004)
10.1016/J.FOODCHEM.2009.07.056
Nano/sub-microsized lignan glycosides from sesame meal exhibit higher transport and absorption efficiency in Caco-2 cell monolayer.
C. Liao (2010)
10.1038/nnano.2007.387
Nanocarriers as an emerging platform for cancer therapy.
D. Peer (2007)
10.1016/j.ejpb.2010.07.011
Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats.
S. Setthacheewakul (2010)
10.2147/IJN.S19259
Enhanced oral bioavailability of cyclosporine A by liposomes containing a bile salt
Peipei Guan (2011)
10.1016/j.addr.2011.05.019
Intestinal lymphatic transport for drug delivery☆
J. Yáñez (2011)
10.1016/S0378-5173(00)00678-5
Covalent coupling of asparagus pea and tomato lectins to poly(lactide) microspheres.
M. Montisci (2001)
10.1152/AJPGI.2001.280.5.G922
The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo.
C. Atuma (2001)
10.1016/S0928-0987(97)10007-0
Binding and uptake of biodegradable poly-DL-lactide micro- and nanoparticles in intestinal epithelia.
S. McClean (1998)
10.1023/A:1012197110917
Comparison of CYP3A Activities in a Subclone of Caco-2 Cells (TC7) and Human Intestine
S. D. Raeissi (2004)
10.1016/j.ijpharm.2009.04.022
Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt.
Y. Chen (2009)
10.1016/j.jconrel.2008.04.016
Multi-functional nanocarriers for targeted delivery of drugs and genes.
L. Jabr-Milane (2008)
10.1016/S0016-5085(87)91069-9
Structural analysis of a human intestinal epithelial cell line.
J. Madara (1987)
10.1007/s11095-010-0130-x
Phospholipids and Lipid-Based Formulations in Oral Drug Delivery
G. Fricker (2010)
10.1016/J.ADDR.2004.09.009
Exploiting receptor biology for oral vaccination with biodegradable particulates.
N. Foster (2005)
10.1002/mabi.201000388
Advances in mucoadhesion and mucoadhesive polymers.
V. Khutoryanskiy (2011)
10.1021/mp9001377
Adenoviral transduction of enterocytes and M-cells using in vitro models based on Caco-2 cells: the coxsackievirus and adenovirus receptor (CAR) mediates both apical and basolateral transduction.
Filippos Kesisoglou (2010)
10.1016/j.tiv.2010.08.009
Caco-2/TC7 cell line characterization for intestinal absorption: how reliable is this in vitro model for the prediction of the oral dose fraction absorbed in human?
L. Turco (2011)
10.1016/j.ijpharm.2010.06.039
Synthesis and in vitro evaluation of potential sustained release prodrugs via targeting ASBT.
Xiaowan Zheng (2010)
10.2165/00003088-200847100-00003
Towards Quantitative Prediction of Oral Drug Absorption
J. Dressman (2008)
10.1016/J.JCONREL.2006.08.013
Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach.
A. des Rieux (2006)
10.1016/j.ejpb.2008.09.003
Lipid nanoparticles for parenteral delivery of actives.
Medha D. Joshi (2009)
10.1016/j.jconrel.2011.06.009
Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics.
William B. Liechty (2011)
10.1016/J.ADDR.2005.09.019
Dendrimer biocompatibility and toxicity.
R. Duncan (2005)
10.1016/j.jconrel.2010.11.022
G3.5 PAMAM dendrimers enhance transepithelial transport of SN38 while minimizing gastrointestinal toxicity.
Deborah S. Goldberg (2011)
10.1016/j.ejps.2011.08.001
Enhanced bioavailability of nano-sized chitosan-atorvastatin conjugate after oral administration to rats.
M. Anwar (2011)
10.1016/S0378-5173(99)00254-9
Lectin-mediated transport of nanoparticles across Caco-2 and OK cells.
G. J. Russell-Jones (1999)
10.1152/AJPCELL.1993.264.5.C1327
Isolation of plasma membrane fractions from the intestinal epithelial model T84.
P. Kaoutzani (1993)
10.1136/gut.29.8.1035
Measurement of gastrointestinal pH profiles in normal ambulant human subjects.
D. F. Evans (1988)
10.1016/S0378-5173(03)00161-3
Prediction of human intestinal permeability using artificial membrane permeability.
Kiyohiko Sugano (2003)
10.3109/03639045.2010.541262
New perspective for the treatment of Alzheimer diseases: Liposomal rivastigmine formulations
N. Mutlu (2011)
Perspectives of biodegradable natural polysaccharides for site-specific drug delivery to the colon.
A. Jain (2007)
10.1093/toxsci/kfq219
Characterization of cellular uptake of perfluorooctanoate via organic anion-transporting polypeptide 1A2, organic anion transporter 4, and urate transporter 1 for their potential roles in mediating human renal reabsorption of perfluorocarboxylates.
Ching-Hui Yang (2010)
10.1016/S0169-409X(00)00129-0
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
C. Lipinski (1997)
10.1002/(SICI)1520-6017(200001)89:1<63::AID-JPS7>3.0.CO;2-6
Caco-2 versus Caco-2/HT29-MTX co-cultured cell lines: permeabilities via diffusion, inside- and outside-directed carrier-mediated transport.
C. Hilgendorf (2000)
10.1615/CRITREVTHERDRUGCARRIERSYST.V28.I1.10
Engineered PLGA nanoparticles: an emerging delivery tool in cancer therapeutics.
A. Jain (2011)
10.2217/nnm.11.67
Dendrimer pharmacokinetics: the effect of size, structure and surface characteristics on ADME properties.
L. M. Kaminskas (2011)
10.1023/A:1025088628787
Quantitative Evaluation of the Function of Small Intestinal P-Glycoprotein: Comparative Studies Between in Situ and in Vitro
Y. Adachi (2004)
10.2217/nnm.10.71
Polymer-drug conjugates for novel molecular targets.
J. Sanchis (2010)
10.1016/S0928-0987(99)00007-X
Mucus as a barrier to the permeability of hydrophilic and lipophilic compounds in the absence and presence of sodium taurocholate micellar systems using cell culture models.
C. Meaney (1999)
10.1016/j.ijpharm.2011.01.060
Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa.
S. Dünnhaupt (2011)
10.1023/A:1015396825274
Pharmaceutical Strategies Utilizing Recombinant Human Serum Albumin
Victor Tuan Giam Chuang (2004)
10.1023/A:1016054306763
Preparation and Characterization of Freeze-dried Chitosan-Poly(Ethylene Oxide) Hydrogels for Site-Specific Antibiotic Delivery in the Stomach
V. Patel (2004)
10.1016/j.jconrel.2010.11.003
Palatal mucosa as a route for systemic drug delivery: A review.
P. Shakya (2011)
10.1016/j.biomaterials.2009.08.030
The characteristics, biodistribution and bioavailability of a chitosan-based nanoparticulate system for the oral delivery of heparin.
M. Chen (2009)
10.1016/j.nano.2009.04.008
Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery.
B. Mishra (2010)
10.1021/JM970530E
Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes.
M. Kansy (1998)
10.1084/JEM.184.3.1045
Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting
A. Frey (1996)
10.1016/j.ijfoodmicro.2010.03.026
Functional cell models of the gut and their applications in food microbiology — A review
A. Cencič (2010)
Ultrastructural changes in rat Paneth and goblet cells after the administration of interferon-alpha.
O. Ozcan (1996)
10.1016/j.ejps.2008.08.008
In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors.
A. Jain (2008)
10.1016/J.ADDR.2005.07.008
Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems.
H. Takeuchi (2005)
10.1002/jps.21961
Paracellular porosity and pore size of the human intestinal epithelium in tissue and cell culture models.
Johanna Linnankoski (2010)
10.1016/0005-2736(94)90337-9
Calcitonin-loaded liposomes: stability under acidic conditions and bile salts-induced disruption resulting in calcitonin-phospholipid complex formation.
A. Ariën (1994)
10.1080/10611860701289719
Design and development of folate appended liposomes for enhanced delivery of 5-FU to tumor cells
Yashwant Gupta (2007)
10.1002/wnan.131
Topical and mucosal liposomes for vaccine delivery.
E. Romero (2011)
10.1111/j.1462-5822.2004.00391.x
Expression and distribution of β1 integrins in in vitro‐induced M cells: implications for Yersinia adhesion to Peyer's patch epithelium
N. Hamzaoui (2004)
10.1002/JPS.21183
Past, present, and future technologies for oral delivery of therapeutic proteins.
R. Singh (2008)
10.1007/BF02209146
Physiological regulation of transepithelial impedance in the intestinal mucosa of rats and hamsters
J. Pappenheimer (2005)
Expression of caveolin-1 and polarized formation of invaginated caveolae in Caco-2 and MDCK II cells.
U. Vogel (1998)
10.1016/0141-0229(90)90090-D
Solid phase membrane mimetics: immobilized artificial membranes.
C. Pidgeon (1990)
10.1002/JPS.20206
Contribution of the paracellular route to the pH-dependent epithelial permeability to cationic drugs.
Naoki Nagahara (2004)
10.1016/S0378-5173(03)00391-0
Transport mechanism(s) of poly (amidoamine) dendrimers across Caco-2 cell monolayers.
M. Elsayed (2003)
10.1016/j.jaut.2009.11.006
Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract.
J. Powell (2010)
10.1016/J.EJPS.2003.10.009
PAMPA--a drug absorption in vitro model 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones.
M. Bermejo (2004)
10.1016/J.JCONREL.2003.12.006
The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability.
A. D’Emanuele (2004)
10.1146/ANNUREV.PH.57.030195.003025
The hydrophobic barrier properties of gastrointestinal mucus.
L. Lichtenberger (1995)
10.1016/S0928-0987(03)00169-6
Intestinal membrane transport of drugs and nutrients: genomics of membrane transporters using expression microarrays.
P. Anderle (2004)
10.1208/s12249-010-9563-0
Recent Advances in Lipid Nanoparticle Formulations with Solid Matrix for Oral Drug Delivery
S. Das (2010)
10.1016/J.EJPB.2005.04.006
Poly (lactide-co-glycolide) particles of different physicochemical properties and their uptake by peyer's patches in mice.
Monjed Shakweh (2005)
10.1016/j.ejpb.2010.06.007
Polymeric micelles for oral drug delivery.
G. Gaucher (2010)
10.1016/j.ijpharm.2011.02.047
Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.
X. Qi (2011)
10.1208/s12249-007-9021-9
Development of Novel Biodegradable Polymeric Nanoparticles-in-Microsphere Formulation for Local Plasmid DNA Delivery in the Gastrointestinal Tract
M. Bhavsar (2007)
10.1016/S1359-6446(04)03354-9
Cell culture-based models for intestinal permeability: a critique.
P. Balimane (2005)
10.1016/j.bbrc.2011.10.108
Barrier characteristics of epithelial cultures modelling the airway and intestinal mucosa: a comparison.
D. Vllasaliu (2011)
10.1177/026119290503300618
An Inter-laboratory Study to Evaluate the Effects of Medium Composition on the Differentiation and Barrier Function of Caco-2 Cell Lines
F. Zucco (2005)
10.1186/1471-2172-6-4
The mannose receptor is expressed by subsets of APC in non-lymphoid organs
S. Linehan (2004)
10.1016/S0169-409X(01)00147-8
An examination of the factors affecting intestinal lymphatic transport of dietary lipids.
B. K. Nordskog (2001)
10.1016/j.yexmp.2008.12.004
Nanoparticle-based targeted drug delivery.
R. Singh (2009)
10.1016/S0928-0987(01)00175-0
Oral vaccination in man using antigens in particles: current status.
D. Brayden (2001)
10.1152/ajpgi.1999.276.5.G1094
Dissociation between growth arrest and differentiation in Caco-2 subclone expressing high levels of sucrase.
J. Tian (1999)
10.1016/j.ctrv.2011.01.006
Liposome based delivery systems in pancreatic cancer treatment: from bench to bedside.
F. Yang (2011)
10.1016/j.biomaterials.2011.05.079
Oral bioavailability, therapeutic efficacy and reactive oxygen species scavenging properties of coenzyme Q10-loaded polymeric nanoparticles.
N. K. Swarnakar (2011)
10.1146/annurev.anchem.1.031207.112747
Liposomes: technologies and analytical applications.
A. Jesorka (2008)
10.2174/157341305774642939
Nanoparticle Formulation Increases Oral Bioavailability of Poorly Soluble Drugs: Approaches Experimental Evidences and Theory.
L. Jia (2005)
10.1016/S0142-9612(02)00445-3
In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis.
D. Fischer (2003)
10.1023/B:PHAM.0000008043.71001.43
Development of a 7-Day, 96-Well Caco-2 Permeability Assay with High-Throughput Direct UV Compound Analysis
J. Alsenz (2004)
10.1016/J.ADDR.2005.09.012
Dendrimer-drug interactions.
A. D’Emanuele (2005)
10.1111/j.2042-7158.2010.01024.x
Lipid nanoparticles for the delivery of poorly water‐soluble drugs
H. Bunjes (2010)
10.1097/01.CAD.0000167902.53039.5A
Liposomal encapsulated anti-cancer drugs.
R. Hofheinz (2005)
10.1289/ehp.7339
Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles
G. Oberdörster (2005)
10.1080/03639040802130061
Lipid Nanoparticles with a Solid Matrix (SLN®, NLC®, LDC®) for Oral Drug Delivery
M. Muchow (2008)
10.1007/s11095-008-9657-5
Evaluation of Bioadhesive Capacity and Immunoadjuvant Properties of Vitamin B12-Gantrez Nanoparticles
Hesham H. Salman (2008)
10.1002/(SICI)1520-6017(200004)89:4<429::AID-JPS1>3.0.CO;2-J
Intestinal permeation enhancers.
B. Aungst (2000)
10.1016/J.IJPHARM.2006.02.019
Controlled release of a self-emulsifying formulation from a tablet dosage form: stability assessment and optimization of some processing parameters.
S. Nazzal (2006)
10.1016/J.IJPHARM.2006.09.030
Investigation of pluronic and PEG-PE micelles as carriers of meso-tetraphenyl porphine for oral administration.
Zerrin Sezgin (2007)
10.4155/fmc.11.149
Drug-permeability and transporter assays in Caco-2 and MDCK cell lines.
D. Volpe (2011)
10.1016/j.jconrel.2009.01.011
Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption.
M. Rekha (2009)
10.1023/A:1022359300826
Isolation and Characterization of Caco-2 Subclones Expressing High Levels of Multidrug Resistance Protein Efflux Transporter
K. Horie (2004)
10.1016/J.IJPHARM.2005.01.022
Current strategies used to enhance the paracellular transport of therapeutic polypeptides across the intestinal epithelium.
Nazila Salamat-Miller (2005)
10.1124/dmd.107.018036
Sulfotransferase Forms Expressed in Human Intestinal Caco-2 and TC7 Cells at Varying Stages of Differentiation and Role in Benzo[a]pyrene Metabolism
W. Meinl (2008)
10.2174/1568026013395100
Physicochemical Profiling (Solubility, Permeability and Charge State)
A. Avdeef (2001)
10.1016/j.ijpharm.2010.12.039
Nano-encapsulations liberated from barley protein microparticles for oral delivery of bioactive compounds.
Ruoxi Wang (2011)
10.1024/0300-9831/a000038
The use of caco-2 cells to estimate fe absorption in humans--a critical appraisal.
A. Sandberg (2010)
10.1007/s11095-007-9517-8
A Novel Design of Artificial Membrane for Improving the PAMPA Model
X. Chen (2007)
10.2165/00003088-200645100-00002
Nanomedicine: clinical applications of polyethylene glycol conjugated proteins and drugs.
S. Parveen (2006)
10.1023/A:1011063232257
Tetanus Toxoid Loaded Nanoparticles from Sulfobutylated Poly(Vinyl Alcohol)-Graft-Poly(Lactide-co-Glycolide): Evaluation of Antibody Response After Oral and Nasal Application in Mice
T. Jung (2004)
10.1021/JS970332A
Human intestinal permeability.
H. Lennernäs (1998)
10.1016/J.JCONREL.2005.03.033
Salmonella-like bioadhesive nanoparticles.
Hesham H. Salman (2005)
10.1177/0883911503018001002
Influence of Surface Chemistry of Poly(Amidoamine) Dendrimers on Caco-2 Cell Monolayers
M. Elsayed (2003)
10.1023/A:1018972102702
Drug Absorption Limited by P-Glycoprotein-Mediated Secretory Drug Transport in Human Intestinal Epithelial Caco-2 Cell Layers
J. Hunter (2004)
10.2174/156720107780362339
Recent advances in protein and peptide drug delivery systems.
Dhirendra Kumar Malik (2007)
10.1163/156856208786440479
Engineering strategies to enhance nanoparticle-mediated oral delivery
Yvonne J. Yamanaka (2008)
10.1002/JPS.10395
The role of surfactants in the reversal of active transport mediated by multidrug resistance proteins.
K. Bogman (2003)
10.1002/JPS.10573
Biodegradable nanoparticles containing protein‐fatty acid complexes for oral delivery of salmon calcitonin
H. Yoo (2004)
10.1016/J.JCONREL.2004.10.022
Self-assembling PEG-p(CL-co-TMC) copolymers for oral delivery of poorly water-soluble drugs: a case study with risperidone.
L. Ould-Ouali (2005)
10.1016/S0939-6411(02)00089-9
Effect of bovine serum albumin on drug permeability estimation across Caco-2 monolayers.
P. Saha (2002)
10.1016/J.EJPB.2006.08.017
In vitro evaluation of the mucoadhesive properties of polysaccharide-based nanoparticulate oral drug delivery systems.
Siwar Chayed (2007)
10.1016/j.jconrel.2009.04.022
Transepithelial transport of PEGylated anionic poly(amidoamine) dendrimers: implications for oral drug delivery.
D. Sweet (2009)
10.1023/A:1013018111829
Gliadin Nanoparticles as Carriers for the Oral Administration of Lipophilic Drugs. Relationships Between Bioadhesion and Pharmacokinetics
M. A. Arangoa (2004)
10.1126/SCIENCE.1078192
Micellar Nanocontainers Distribute to Defined Cytoplasmic Organelles
R. Savić (2003)
10.1016/j.ijpharm.2008.05.016
Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: II. In vitro transport study.
S. V. R. Rao (2008)
10.1074/jbc.273.34.21950
Binding and Transcytosis of Botulinum Neurotoxin by Polarized Human Colon Carcinoma Cells*
A. B. Maksymowych (1998)
10.1023/A:1019854327540
Comparative Uptake Studies of Bioadhesive and Non-Bioadhesive Nanoparticles in Human Intestinal Cell Lines and Rats: The Effect of Mucus on Particle Adsorption and Transport
I. Behrens (2004)
10.1016/J.EJPS.2005.04.015
Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium.
A. des Rieux (2005)
10.4103/0250-474X.84576
Polymers for Colon Targeted Drug Delivery
H. Rajpurohit (2010)
10.1016/J.BIOCEL.2007.05.009
Reversible differentiation of Caco-2 cells reveals galectin-9 as a surface marker molecule for human follicle-associated epithelia and M cell-like cells.
Julia F. Pielage (2007)
10.1007/s00018-009-0053-z
Nanocarriers’ entry into the cell: relevance to drug delivery
H. Hillaireau (2009)
10.1016/j.biomaterials.2009.02.045
Poly(lactide)-vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel.
S. Feng (2009)
10.1016/J.EJPS.2004.11.011
Caco-2 permeability of weakly basic drugs predicted with the Double-Sink PAMPA method
A. Avdeef (2005)
10.1021/BM0503165
Exploiting the vitamin B12 pathway to enhance oral drug delivery via polymeric micelles.
M. Francis (2005)
10.1016/j.addr.2008.08.002
Hydrogel nanoparticles in drug delivery.
M. Hamidi (2008)
10.1016/j.ijpharm.2009.07.008
Proliposomes of exemestane for improved oral delivery: formulation and in vitro evaluation using PAMPA, Caco-2 and rat intestine.
P. Hiremath (2009)
10.1002/JBM.A.30243
Cellular evaluation of oral chemotherapy carriers.
J. Blanchette (2005)
10.1034/j.1600-065X.2003.00072.x
Structure, lymphatic vascularization and lymphocyte migration in mucosa‐associated lymphoid tissue
G. Azzali (2003)
10.1023/A:1016085108889
Gastrointestinal Uptake of Biodegradable Microparticles: Effect of Particle Size
M. P. Desai (2004)
10.1002/JPS.21155
Enhanced oral bioavailability of doxorubicin in a dendrimer drug delivery system.
Weilun Ke (2008)
10.1016/J.TIM.2004.09.002
Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa.
H. C. Ramos (2004)
10.1016/j.cbpa.2010.10.008
Protein-polymer conjugates: synthetic approaches by controlled radical polymerizations and interesting applications.
G. Grover (2010)
10.1155/2012/750891
Current State-of-Art and New Trends on Lipid Nanoparticles (SLN and NLC) for Oral Drug Delivery
P. Severino (2012)
10.1586/erd.09.43
Challenges and advances in nanoparticle-based oral insulin delivery
Rekha M Ramesan (2009)
10.1016/J.JCONREL.2004.03.022
Transport of dendrimer nanocarriers through epithelial cells via the transcellular route.
R. Jevprasesphant (2004)
10.1023/A:1025032511040
pH-Dependent Bidirectional Transport of Weakly Basic Drugs Across Caco-2 Monolayers: Implications for Drug–Drug Interactions
Sibylle Neuhoff (2004)
10.1016/j.ejpb.2009.06.001
Lipid--an emerging platform for oral delivery of drugs with poor bioavailability.
S. Chakraborty (2009)
10.1016/j.ijpharm.2011.04.042
Cytotoxicity and biocompatibility evaluation of a poly(magnesium acrylate) hydrogel synthesized for drug delivery.
Maha Cheddadi (2011)
10.1016/j.vetpar.2011.05.028
Nanomedicine: novel approaches in human and veterinary therapeutics.
J. M. Irache (2011)
10.1007/s11095-005-8418-y
Design of Estradiol Loaded PLGA Nanoparticulate Formulations: A Potential Oral Delivery System for Hormone Therapy
S. Hariharan (2005)
10.2217/nnm.10.10
Nanomicellar formulations for sustained drug delivery: strategies and underlying principles.
Ruchit Trivedi (2010)
10.1016/j.copbio.2011.06.003
Polymer--drug conjugates as nano-sized medicines.
F. Canal (2011)
10.1016/J.JCONREL.2007.09.013
Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives.
R. C. Mundargi (2008)
10.1016/j.jconrel.2009.08.010
Lipid nanocarriers improve paclitaxel transport throughout human intestinal epithelial cells by using vesicle-mediated transcytosis.
E. Roger (2009)
10.1023/B:PHAM.0000041452.08005.b0
Biodegradable Self-Assembling PEG-Copolymer as Vehicle for Poorly Water-Soluble Drugs
L. Ould-Ouali (2004)
10.2174/138920012802850047
Toxicological profile of therapeutic nanodelivery systems.
Luis M Bimbo (2012)
10.2217/nnm.09.110
Biopharmaceutical parameters to consider in order to alter the fate of nanocarriers after oral delivery.
E. Roger (2010)
10.1016/S1056-8719(00)00113-1
Current methodologies used for evaluation of intestinal permeability and absorption.
P. Balimane (2000)
10.1016/j.ejps.2010.05.002
Intestinal permeability enhancement of levothyroxine sodium by straight chain fatty acids studied in MDCK epithelial cell line.
Dimple Pabla (2010)
10.1016/j.addr.2011.05.017
Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles.
S. Cai (2011)
10.1016/S0928-0987(00)00141-X
Analysis of drug transport and metabolism in cell monolayer systems that have been modified by cytochrome P4503A4 cDNA-expression.
C. Crespi (2000)
10.2147/IJN.S596
Drug delivery and nanoparticles: Applications and hazards
W. D. de Jong (2008)
10.1007/s11095-006-9223-y
Functionalized Micellar Systems for Cancer Targeted Drug Delivery
Damon M Sutton (2006)
10.1002/JPS.2600841011
Passive diffusion of weak organic electrolytes across Caco-2 cell monolayers: uncoupling the contributions of hydrodynamic, transcellular, and paracellular barriers.
A. Adson (1995)
10.1016/j.addr.2011.09.010
Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.
S. Sadekar (2012)
10.2147/IJN.S17296
Recent advances of chitosan nanoparticles as drug carriers
J. Wang (2011)
10.1080/10611860410001693706
Issues in Oral Nanoparticle Drug Carrier Uptake and Targeting
A. Florence (2004)
10.1016/s0021-9258(18)82166-4
Fatty acid esterification during differentiation of the human intestinal cell line Caco-2.
P. J. Trotter (1993)
10.1002/mabi.201100193
Copolymers: efficient carriers for intelligent nanoparticulate drug targeting and gene therapy.
M. Hamidi (2012)
10.1016/j.jconrel.2008.07.017
Cellular accumulation and cytotoxicity of macromolecular platinum complexes in cisplatin-resistant tumor cells.
D. Garmann (2008)
10.1016/j.biomaterials.2009.02.036
Development of pH-responsive chitosan/heparin nanoparticles for stomach-specific anti-Helicobacter pylori therapy.
Y. Lin (2009)
10.1021/mp700089s
Endocytosis inhibitors prevent poly(amidoamine) dendrimer internalization and permeability across Caco-2 cells.
Kelly M. Kitchens (2008)
10.1016/J.IJPHARM.2006.02.018
Polyethylene glycol-phosphatidylethanolamine conjugate (PEG-PE)-based mixed micelles: some properties, loading with paclitaxel, and modulation of P-glycoprotein-mediated efflux.
Rupa D. Dabholkar (2006)
10.1016/J.TUBE.2005.08.009
Oral solid lipid nanoparticle-based antitubercular chemotherapy.
R. Pandey (2005)
10.1021/bp050208u
Role of Caco‐2 Cell Monolayers in Prediction of Intestinal Drug Absorption
Pranav J. Shah (2006)
10.1023/B:PHAM.0000016249.52831.a5
Uptake and Cytotoxicity of Chitosan Molecules and Nanoparticles: Effects of Molecular Weight and Degree of Deacetylation
M. Huang (2004)
10.1016/j.biomaterials.2011.08.087
A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery.
M. Chen (2011)
10.1016/j.ejpb.2008.03.004
Permeation enhancer effect of chitosan and chitosan derivatives: comparison of formulations as soluble polymers and nanoparticulate systems on insulin absorption in Caco-2 cells.
A. Sadeghi (2008)
10.1517/17425247.2.5.843
The potential of chitosan for the oral administration of peptides
C. Prego (2005)
10.1021/bc800076n
Oral delivery of peptide drugs using nanoparticles self-assembled by poly(gamma-glutamic acid) and a chitosan derivative functionalized by trimethylation.
F. Mi (2008)
10.1016/J.EJPS.2005.12.008
PAMPA--a drug absorption in vitro model 13. Chemical selectivity due to membrane hydrogen bonding: in combo comparisons of HDM-, DOPC-, and DS-PAMPA models.
A. Avdeef (2006)
10.1002/JPS.20062
Variation of peptide transporter (PepT1 and HPT1) expression in Caco-2 cells as a function of cell origin.
I. Behrens (2004)
10.2165/00003088-200140020-00001
Bioadhesion: new possibilities for drug administration?
J. Woodley (2001)
10.1023/A:1020483911355
Comparison of Human Duodenum and Caco-2 Gene Expression Profiles for 12,000 Gene Sequences Tags and Correlation with Permeability of 26 Drugs
D. Sun (2004)
10.1016/j.jconrel.2011.06.015
Biodegradable star HPMA polymer-drug conjugates: Biodegradability, distribution and anti-tumor efficacy.
T. Etrych (2011)
10.2174/138920111798377003
Progress in nanoparticulate systems for peptide, proteins and nucleic acid drug delivery.
S. Słomkowski (2011)
10.1074/jbc.M309026200
Enhanced Viscoelasticity of Human Cystic Fibrotic Sputum Correlates with Increasing Microheterogeneity in Particle Transport*
M. Dawson (2003)
10.1021/nn900002m
Impact of nanotechnology on drug delivery.
O. Farokhzad (2009)
10.1016/j.biomaterials.2008.12.054
Poly(amidoamine) dendrimer-drug conjugates with disulfide linkages for intracellular drug delivery.
Y. E. Kurtoglu (2009)
10.1038/nrd1067
Challenges for the oral delivery of macromolecules
M. Goldberg (2003)
Role of intestinal mucus in transepithelial passage of bacteria across the intact ileum in vitro.
C. Albanese (1994)
10.1248/BPB.27.418
Studies on the intestinal absorption of low molecular weight heparin using saturated fatty acids and their derivatives as an absorption enhancer in rats.
S. Mori (2004)
10.1016/j.ejpb.2008.05.017
Transport evaluation of salicylic acid and structurally related compounds across Caco-2 cell monolayers and artificial PAMPA membranes.
M. Koljonen (2008)
10.1016/j.ijpharm.2010.04.039
The characteristics and mechanism of simvastatin loaded lipid nanoparticles to increase oral bioavailability in rats.
Z. Zhang (2010)
10.1016/j.biomaterials.2011.10.075
Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport.
Y. Jin (2012)
10.1016/j.jconrel.2010.03.012
Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly(anhydride) nanoparticles.
M. Agüeros (2010)
10.1021/BM700716C
Biodegradable and pH-sensitive hydrogels for potential colon-specific drug delivery: characterization and in vitro release studies.
M. A. Casadei (2008)
10.1006/BBRC.2000.4038
Expression of specific markers and particle transport in a new human intestinal M-cell model.
E. Gullberg (2000)
10.1023/A:1026166729873
Engineering of Dendrimer Surfaces to Enhance Transepithelial Transport and Reduce Cytotoxicity
R. Jevprasesphant (2004)
10.2174/157016312799304552
Preparation and characterization of solid lipid nanoparticles-a review.
R. Parhi (2012)



This paper is referenced by
10.2217/nnm.13.223
Porous silicon nanoparticles for nanomedicine: preparation and biomedical applications.
H. Santos (2014)
10.1021/acs.molpharmaceut.5b00081
Cysteine-Functionalized Nanostructured Lipid Carriers for Oral Delivery of Docetaxel: A Permeability and Pharmacokinetic Study.
Guihua Fang (2015)
10.3390/pharmaceutics11050222
Systemic Design and Evaluation of Ticagrelor-Loaded Nanostructured Lipid Carriers for Enhancing Bioavailability and Antiplatelet Activity
Gi-Ho Son (2019)
10.2147/IJN.S44487
Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506): in vitro characterization and improved corneal permeation
Yikang Dai (2013)
10.5507/bp.2019.010
Nanodrugs used in cancer therapy.
K. Kopečková (2019)
10.1517/17425247.2014.935336
Diatoms: a biotemplating approach to fabricating drug delivery reservoirs
Joshua Chao (2014)
10.1007/s13273-013-0026-z
Toxicity evaluation of inorganic nanoparticles: considerations and challenges
S. Choi (2013)
10.1007/978-1-4614-8993-1_5
In Vitro Cytotoxicity Assays of Nanoparticles on Different Cell Lines
P. S. Melo (2014)
Nanomedicines, a strategy to evade multidrug resistance
Carolina de Abreu Pereira (2015)
Nanomedicines, a Strategy to Evade Multidrug Resistance
Doutor João Gonçalves (2015)
10.1016/j.biomaterials.2014.07.026
The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium.
F. Araújo (2014)
Porous Silicon-Based Multicomposites for Controlled Drug Delivery
D. Liu (2014)
10.1533/9781908818683.219
Lipids and inorganic nanoparticles in oral insulin delivery
T. A. Sonia (2015)
Development of Self-Microemulsifying Drug Delivery System (SMEDDS) for Poorly Water Soluble Anticancerous Drug
N. Khalid (2017)
10.1002/adma.201400953
Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.
H. Zhang (2014)
10.4155/tde.15.4
Nanoformulation strategies for the enhanced oral bioavailability of antiretroviral therapeutics.
Lee M. Tatham (2015)
10.1016/j.biomaterials.2014.04.104
Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.
N. Shrestha (2014)
10.1016/j.jconrel.2016.06.016
Nanoparticles for oral delivery: Design, evaluation and state-of-the-art.
A. Date (2016)
10.1016/j.jconrel.2016.04.024
Oral hypoglycaemic effect of GLP-1 and DPP4 inhibitor based nanocomposites in a diabetic animal model.
N. Shrestha (2016)
10.2147/IJN.S94013
Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles
D. Desai (2016)
10.1080/10837450.2019.1699109
Enhancement of the intestinal absorption of bortezomib by self-nanoemulsifying drug delivery system
M. Mahmoudian (2019)
10.1007/978-1-4614-9164-4_10
Porous Silicon Nanoparticles
H. Santos (2013)
10.1016/j.addr.2016.08.007
In vitro toxicity assessment of oral nanocarriers.
S. G. Ciappellano (2016)
Hydrogel/polymer micelles composites derived from polymerization of microemulsions for oral drug delivery
Li Chen (2013)
Polymeric formulations for innovative drug delivery systems of nitric oxide in the treatment of inflammatory bowel diseases: formulation and bioavailability assessment
Shefaat Ullah Shah (2015)
10.1016/j.biomaterials.2015.07.045
Multistage pH-responsive mucoadhesive nanocarriers prepared by aerosol flow reactor technology: A controlled dual protein-drug delivery system.
N. Shrestha (2015)
10.1016/B978-0-323-52725-5.00016-2
Oral Administration of Nanoparticles-Based TB Drugs
J. Magalhães (2017)
Glucagon-like peptide-1 and glucagon-like peptide-1 analogs nanotechnology-based systems for prevention and therapy of diabetes
A. F. Araújo (2017)
10.1186/s40360-018-0275-5
Enhancement of saquinavir absorption and accumulation through the formation of solid drug nanoparticles
Gabriel Kigen (2018)
10.1533/9781908818683.113
Oral insulin delivery – challenges and strategies
T. A. Sonia (2015)
10.3109/10717544.2015.1052863
A review of biodegradable polymeric systems for oral insulin delivery
Y. Luo (2016)
10.4155/tde.13.5
Peptide pills for brain diseases? Reality and future perspectives.
D. R. Serrano Lopez (2013)
See more
Semantic Scholar Logo Some data provided by SemanticScholar