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

Poly(ε-caprolactone), Eudragit® RS 100 And Poly(ε-caprolactone)/Eudragit® RS 100 Blend Submicron Particles For The Sustained Release Of The Antiretroviral Efavirenz.

Katia P. Seremeta, D. Chiappetta, A. Sosnik
Published 2013 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
The design of simple and scalable drug delivery systems to target the central nervous system (CNS) could represent a breakthrough in the addressment of the HIV-associated neuropathogenesis. The intranasal (i.n.) route represents a minimally invasive strategy to surpass the blood-brain barrier, though it demands the use of appropriate nanocarriers bearing high drug payloads and displaying sufficiently long residence time. The present work explored the development of submicron particles made of poly(ε-caprolactone) (PCL), Eudragit(®) RS 100 (RS a copolymer of ethylacrylate, methylmethacrylate and methacrylic acid esterified with quaternary ammonium groups) and their blends, loaded with the first-choice antiretroviral efavirenz (EFV) as an approach to fine tune the particle size and the release kinetics. Particles displaying hydrodynamic diameters between 90 and 530 nm were obtained by two methods: nanoprecipitation and emulsion/solvent diffusion/evaporation. In general, the former resulted in smaller particles and narrower size distributions. The encapsulation efficiency was greater than 94%, the drug weight content approximately 10% and the yield in the 72.5-90.0% range. The highly positive surface (>+30 mV) rendered the suspensions physically stable for more than one month. In vitro release assays indicated that the incorporation of the poly(methacrylate) into the composition reduced the burst effect and slowed the release rate down with respect to pure poly(ε-caprolactone) particles. The analysis of the release profile indicated that, in all cases, the kinetics adjusted well to the Higuchi model with R(adj)(2) values >0.9779. These findings suggested that the release was mainly controlled by diffusion. In addition, when data were analyzed by the Korsmeyer-Peppas model, n values were in the 0.520-0.587 range, indicating that the drug release was accomplished by the combination of two phenomena: diffusion and polymer chain relaxation. Based on ATR/FT-IR analysis that investigated drug/polymer matrix interactions, the potential role of the hydrophobic interactions of C-F groups of EFV with carbonyl groups in the backbone of PCL and poly(methacrylate) could be ruled out. The developed EFV-loaded particles appear as a useful platform to investigate the intranasal administration to increase the bioavailability in the CNS.
This paper references
10.1016/j.colsurfb.2010.05.016
Molecular implications in the nanoencapsulation of the anti-tuberculosis drug rifampicin within flower-like polymeric micelles.
M. Moretton (2010)
10.1081/DDC-120014576
Low Molecular Weight Heparin-Loaded Polymeric Nanoparticles: Formulation, Characterization, and Release Characteristics
V. Hoffart (2002)
10.1201/9781420049367
Handbook of Biodegradable Polymers
A. Domb (1998)
Annu
L. Geeraert (2008)
10.1016/J.PROGPOLYMSCI.2011.01.001
Polymer nanoparticles: Preparation techniques and size-control parameters
J. D. Rao (2011)
10.1016/S0378-5173(02)00483-0
BIODEGRADABLE POLY (E-CAPROLACTONE) NANOPARTICLES FOR TUMOR-TARGETED DELIVERY OF TAMOXIFEN
J. S. Chawla (2002)
10.1016/j.bmc.2008.04.064
Synthesis, nano-scale assembly, and in vivo anti-thrombotic activity of novel short peptides containing L-Arg and L-Asp or L-Glu.
Y. Chen (2008)
10.1186/1742-4690-3-S1-S6
History of HAART – the true story of how effective multi-drug therapy was developed for treatment of HIV disease
M. Delaney (2006)
10.1016/j.expneurol.2007.03.007
Highly active antiretroviral therapy of cognitive dysfunction and neuronal abnormalities in SCID mice with HIV encephalitis
Jennifer Cook-Easterwood (2007)
10.2217/nnm.09.90
Efavirenz-loaded polymeric micelles for pediatric anti-HIV pharmacotherapy with significantly higher oral bioavailability [corrected].
D. Chiappetta (2010)
10.1157/13116752
Glucoproteína P e infección por el virus de la inmunodeficiencia humana
G. Peralta (2008)
10.1016/j.actbio.2011.12.020
Hot melt poly-ε-caprolactone/poloxamine implantable matrices for sustained delivery of ciprofloxacin.
A. M. Puga (2012)
10.1016/J.BIOMATERIALS.2006.10.012
Preparation of hemoglobin-loaded nano-sized particles with porous structure as oxygen carriers.
J. Zhao (2007)
10.1016/j.colsurfb.2011.08.009
Incorporation and release behavior of amitriptylene in core-shell-corona type triblock copolymer micelles.
B. P. Bastakoti (2011)
10.1016/j.ijpharm.2009.06.019
Nanoparticles for direct nose-to-brain delivery of drugs.
Alpesh Mistry (2009)
10.1016/J.ADDR.2006.07.026
Intraocular implants for extended drug delivery: therapeutic applications.
J. Bourges (2006)
10.1016/S0891-5520(05)70139-2
Progress in HIV therapeutics and the challenges of adherence to antiretroviral therapy.
L. Andrews (2000)
10.1016/j.ijpharm.2010.06.006
Cytotoxicity assessment of heparin nanoparticles in NR8383 macrophages.
H. Eidi (2010)
10.1007/s11095-008-9710-4
Poly (lactide-co-glycolide)-Polymethacrylate Nanoparticles for Intramuscular Delivery of Plasmid Encoding Interleukin-10 to Prevent Autoimmune Diabetes in Mice
Ashwin Basarkar (2008)
10.1542/peds.2007-2558
Impact of the HIV/AIDS Epidemic on the Neurodevelopment of Preschool-Aged Children in Kinshasa, Democratic Republic of the Congo
A. van Rie (2008)
10.1186/1556-276X-6-260
Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies
V. Sanna (2011)
10.1007/s11481-006-9039-x
Strategies for Intranasal Delivery of Therapeutics for the Prevention and Treatment of NeuroAIDS
L. Hanson (2006)
10.1016/J.PROGPOLYMSCI.2010.04.002
The return of a forgotten polymer : Polycaprolactone in the 21st century
M. Woodruff (2009)
10.1016/0168-3659(87)90035-6
A simple equation for description of solute release II. Fickian and anomalous release from swellable devices
P. L. Ritger (1987)
10.1016/j.ejpb.2007.11.010
Incorporation in polymeric nanocapsules improves the antioxidant effect of melatonin against lipid peroxidation in mice brain and liver.
S. R. Schaffazick (2008)
10.1016/S0169-409X(99)00026-5
Involvement of multiple transporters in the oral absorption of nucleoside analogues.
Balimane (1999)
10.1016/J.JCONREL.2006.03.011
Aminated gelatin microspheres as a nasal delivery system for peptide drugs: evaluation of in vitro release and in vivo insulin absorption in rats.
J. Wang (2006)
10.1016/j.colsurfb.2010.07.047
Preparation and physicochemical characterization of naproxen-PLGA nanoparticles.
Y. Javadzadeh (2010)
10.1002/glia.20725
Regulation of ABC membrane transporters in glial cells: Relevance to the pharmacotherapy of brain HIV‐1 infection
P. T. Ronaldson (2008)
10.1016/J.POLYMER.2003.09.012
Poly(ethylene glycol)-poly(epsilon-caprolactone) block oligomers as injectable materials
A. Sosnik (2003)
10.1016/j.biomaterials.2010.11.082
Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric micelles.
D. Chiappetta (2011)
10.1016/j.ejpb.2010.05.007
N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz.
D. Chiappetta (2010)
10.1016/j.addr.2009.11.020
Nanotechnology applications for improved delivery of antiretroviral drugs to the brain.
H. L. Wong (2010)
10.1007/s12026-010-8166-x
Thinking about HIV: the intersection of virus, neuroinflammation and cognitive dysfunction
K. Grovit-Ferbas (2010)
10.1002/jps.21372
Interactions of pluronic block copolymers on P-gp efflux activity: experience with HIV-1 protease inhibitors.
N. Shaik (2008)
10.1016/S0169-409X(99)00022-8
P-glycoprotein, secretory transport, and other barriers to the oral delivery of anti-HIV drugs.
Aungst (1999)
10.1016/j.jcis.2008.03.033
Strategies to control the particle size distribution of poly-epsilon-caprolactone nanoparticles for pharmaceutical applications.
Federica Lince (2008)
10.1002/jps.21723
Investigation of the micellar effect of pluronic P85 on P-glycoprotein inhibition: cell accumulation and equilibrium dialysis studies.
N. Shaik (2009)
[The mechanism of degradation for the absorbable biomaterials poly(epsilon-caprolactone) in vitro and in vivo].
J. Chen (1997)
10.1124/JPET.104.076216
P-Glycoprotein and Mutlidrug Resistance-Associated Proteins Limit the Brain Uptake of Saquinavir in Mice
Seonghee Park (2005)
10.1002/jps.21924
Intranasal delivery to the central nervous system: mechanisms and experimental considerations.
S. Dhuria (2010)
10.1586/eri.10.179
Impact of current antiretroviral therapies on neuroAIDS
P. Vivithanaporn (2011)
10.1211/0022357022539
Is nose‐to‐brain transport of drugs in man a reality?
L. Illum (2004)
10.1016/j.bcp.2011.07.081
Efavirenz is a substrate and in turn modulates the expression of the efflux transporter ABCG2/BCRP in the gastrointestinal tract of the rat.
R. Peroni (2011)
10.1016/S0168-3659(02)00272-9
Development of an injection molded poly(ε-caprolactone) intravaginal insert for the delivery of progesterone to cattle
M. Rathbone (2002)
10.1016/J.BIOMATERIALS.2005.10.035
PEO-PPO-PEO-based poly(ether ester urethane)s as degradable reverse thermo-responsive multiblock copolymers.
D. Cohn (2006)
10.1523/JNEUROSCI.5473-10.2011
Loss of Neuronal Integrity during Progressive HIV-1 Infection of Humanized Mice
P. Dash (2011)
10.1002/ccd.24331
Local delivery of sirolimus nanoparticles for the treatment of in‐stent restenosis
A. Zago (2013)
Curr
F. Romanelli (2006)
10.1101/GR.184901
The human ATP-binding cassette (ABC) transporter superfamily.
M. Dean (2001)
10.1038/nature05630
Multiple molecular mechanisms for multidrug resistance transporters
C. Higgins (2007)
10.1016/0168-3659(87)90034-4
A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs
P. L. Ritger (1987)
10.1016/j.addr.2009.11.021
Surface modifications of nanocarriers for effective intracellular delivery of anti-HIV drugs.
S. Gunaseelan (2010)
10.1007/s11095-006-9101-7
Intracellular Delivery of Saquinavir in Biodegradable Polymeric Nanoparticles for HIV/AIDS
Lipa K Shah (2006)
10.1016/J.BIOMATERIALS.2005.09.019
The in vivo degradation, absorption and excretion of PCL-based implant.
H. Sun (2006)
Exp
S. Park (2005)
10.1097/01.wco.0000236614.51592.ca
Influence of highly active antiretroviral therapy on persistence of HIV in the central nervous system
A. Nath (2006)
10.1208/s12248-009-9169-1
Evaluation of Mucoadhesive PLGA Microparticles for Nasal Immunization
Dilip Pawar (2009)
10.1002/APP.33664
Fast and efficient synthesis of high molecular weight poly(epsilon-caprolactone) diols by microwave-assisted polymer synthesis
Gustavo Gotelli (2011)
10.1146/ANNUREV.MED.59.062806.123001
Hide-and-seek: the challenge of viral persistence in HIV-1 infection.
Luc Geeraert (2008)
10.1016/S0928-0987(01)00095-1
Modeling and comparison of dissolution profiles.
P. Costa (2001)
10.1157/13116752
REVISIÓNGlucoproteína P e infección por el virus de la inmunodeficiencia humanaP-glycoprotein and human immunodeficiency virus infection
G. Peralta (2008)
10.1016/J.COLSURFA.2005.10.064
The effect of type of organic phase solvents on the particle size of poly(d,l-lactide-co-glycolide) nanoparticles
K. Song (2006)
10.2217/nnm.09.38
NanoART, neuroAIDS and CNS drug delivery.
Ari S. Nowacek (2009)
10.3390/ijms10031045
Molecular Pathology of Neuro-AIDS (CNS-HIV)
L. Crews (2009)
10.2174/138161206776055868
Use of virostatics as a means of targeting human immunodeficiency virus infection.
F. Romanelli (2006)
10.1016/S0169-409X(01)00219-8
Biodegradable block copolymers.
N. Kumar (2001)
10.1016/J.EJPB.2007.03.022
Poly(ethylene oxide)-poly(propylene oxide) block copolymer micelles as drug delivery agents: improved hydrosolubility, stability and bioavailability of drugs.
D. Chiappetta (2007)
10.1016/j.jconrel.2009.05.007
Drug delivery systems in HIV pharmacotherapy: what has been done and the challenges standing ahead.
A. Sosnik (2009)
Retrovirology 3 (2006) S6
M. Delaney (2006)
10.1002/JPS.2600780613
Blood clearance and organ distribution of intravenously administered polymethacrylic nanoparticles in mice.
A. Rolland (1989)
10.1016/j.ejpb.2009.02.013
The use of Eudragit RS 100/cyclodextrin nanoparticles for the transmucosal administration of glutathione.
A. Lopedota (2009)
Infect
L. Andrews (2000)
10.1016/S0891-5520(05)70215-4
Bartonellosis. New and old.
C. Maguiña (2000)
10.3109/10611860903483396
Intranasal drug delivery of didanosine-loaded chitosan nanoparticles for brain targeting; an attractive route against infections caused by aids viruses
Abeer M. Al-Ghananeem (2010)
10.1070/MC2003V013N02ABEH001690
Effect of the type of hydrophobic polymers on the size of nanoparticles obtained by emulsification–solvent evaporation
Yulia V. Chernysheva (2003)



This paper is referenced by
10.17113/ftb.57.03.19.6035
Silica-Lipid Hybrid Microparticles as Efficient Vehicles 
for Enhanced Stability and Bioaccessibility of Curcumin
Yudi Ma (2019)
Preparation of submicron particles for theranostic applications : imaging and therapy
M. Iqbal (2015)
10.1007/978-1-4939-1655-9_30
Humanized Mice as a Platform for the Development of Long-Acting Nanoformulated Antiretroviral Therapy
J. McMillan (2014)
10.1201/B20045-18
Aliphatic Polyester Protein Drug Delivery Systems
M. N. V. Ravi Kumar (2017)
10.1016/j.cis.2015.05.003
Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers.
A. Sosnik (2015)
10.18178/IJSSH.2016.V6.766
Social and Psychological Challenges of the 21st Century and Beyond
Robert J. Taormina (2016)
Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus: Drug Development and Industrial Pharmacy: Vol 0, No 0
Zênia Maria Maciel Lavra (2016)
10.1002/EJLT.201600167
Enhanced oral bioavailability of quercetin by a new non‐aqueous self‐double‐emulsifying drug delivery system
Q. Wang (2017)
10.1208/s12249-017-0854-6
Optimization of Curcuma Oil/Quinine-Loaded Nanocapsules for Malaria Treatment
G. Gomes (2017)
10.1080/07373937.2016.1186685
In situ observation on particle formation process via single droplet drying apparatus: Effects of precursor composition on particle morphology
Nan Fu (2016)
10.1016/j.colsurfb.2017.11.050
Nanoparticulate delivery systems for alkyl gallates: Influence of the elaboration process on particle characteristics, drug encapsulation and in-vitro release.
A. Chebil (2018)
10.1016/j.micpath.2019.03.007
Characterisation and anti-biofilm activity of glycerol monolaurate nanocapsules against Pseudomonas aeruginosa.
L. Q. Lopes (2019)
10.1080/17425247.2016.1182487
Plant extracts: from encapsulation to application
Brenda Armendáriz-Barragán (2016)
10.3390/pharmaceutics10020039
Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?
A. Dalpiaz (2018)
10.1016/j.biopha.2019.109014
Cationic and anionic unloaded polymeric nanocapsules: Toxicological evaluation in rats shows low toxicity.
Muriel Pando Pereira (2019)
10.1080/15685551.2014.907614
Development of pH-sensitive polycaprolactone-based microspheres for in vitro release studies of Triprolidine Hydrochloride
K. Sudhakar (2014)
10.1016/j.colsurfb.2013.06.035
A novel nanoparticulate system for sustained delivery of acid-labile lansoprazole.
M. Alai (2013)
10.1007/s13346-017-0446-8
Finding key nanoprecipitation variables for achieving uniform polymeric nanoparticles using neurofuzzy logic technology
Miguel O. Jara (2017)
10.1080/03639045.2016.1205598
Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus
Zênia Maria Maciel Lavra (2017)
Análisis sistemático de variables determinantes en la producción de nanopartículas poliméricas de Eudragit® RS, RL y PCL por el método de nanoprecipitación
J. González (2016)
10.1016/j.biopha.2016.02.039
Mixed surfactant based (SNEDDS) self-nanoemulsifying drug delivery system presenting efavirenz for enhancement of oral bioavailability.
P. Senapati (2016)
10.1007/978-3-030-00545-0
Natural Products as Source of Molecules with Therapeutic Potential: Research & Development, Challenges and Perspectives
V. Filho (2018)
10.1016/j.msec.2020.111315
Taste-masked nanoparticles containing Saquinavir for pediatric oral administration.
Katherine Krieser (2020)
10.1080/17425247.2019.1583206
Approaches for CNS delivery of drugs – nose to brain targeting of antiretroviral agents as a potential attempt for complete elimination of major reservoir site of HIV to aid AIDS treatment
S. Gupta (2019)
10.1007/s00396-014-3260-6
Compressed antisolvent process for polymer coating of drug-loaded aerogel nanoparticles and study of the release behavior
Nerea Murillo-Cremaes (2014)
10.1007/978-1-4614-5836-4_116
Nanomedicines for nervous system diseases
Dongwei Guo (2014)
10.1007/978-3-319-41421-8_2
Nanoprecipitation Process: From Particle Preparation to In Vivo Applications
Karim Miladi (2016)
10.1016/j.biomaterials.2014.01.041
Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging.
F. Ye (2014)
DEVELOPMENT AND CHARACTERIZATION OF POLYCAPROLACTONE (PCL)/POLY ((R)-3-HYDROXYBUTYRIC ACID) (PHB) BLEND MICROSPHERES FOR TAMOXIFEN DRUG RELESE STUDIES
P. K. Babu (2015)
10.4103/1735-5362.199041
Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles
S. Salatin (2017)
10.1007/s40199-018-0230-4
Correction to: A systematic review of nano formulation of natural products for the treatment of inflammatory bowel disease: drug delivery and pharmacological targets
Yasamin Davatgaran Taghipour (2018)
10.2147/DDDT.S170676
Preparation and characterization of pH-sensitive nanoparticles of budesonide for the treatment of ulcerative colitis
Hong Zhou (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar