← Back to Search
PEGylated PLGA Nanospheres Optimized By Design Of Experiments For Ocular Administration Of Dexibuprofen-in Vitro, Ex Vivo And In Vivo Characterization.
E. Sánchez-López, M. Egea, A. Cano, M. Espina, A. Calpena, M. Ettcheto, A. Camins, E. Souto, A. Silva, M. García
Published 2016 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceutical profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomer of ibuprofen and therefore lower doses may be applied to achieve the same therapeutic level. According to this, two batches of nanospheres of different drug concentrations, 0.5 and 1.0mg/ml respectively, have been developed (the latter corresponding to the therapeutic ibuprofen concentration for inflammatory eye diseases). Both batches were composed of negatively charged nanospheres (--14.1 and --15.9mV), with a mean particle size below 200nm, and a high encapsulation efficiency (99%). X-ray, FTIR, and DSC analyses confirmed that the drug was dispersed inside the matrix of the nanospheres. While the in vitro release profile was sustained up to 12h, the ex vivo corneal and scleral permeation profile demonstrated higher drug retention and permeation in the corneal tissue rather than in the sclera. These results were also confirmed by the quantification of dexibuprofen in ocular tissues after the in vivo administration of drug-loaded nanospheres. Cell viability studies confirmed that PEGylated-PLGA nanospheres were less cytotoxic than free dexibuprofen in the majority of the tested concentrations. Ocular in vitro (HET-CAM test) and in vivo (Draize test) tolerance assays demonstrated the non-irritant character of both nanosphere batches. In vivo anti-inflammatory effects were evaluated in albino rabbits before and after inflammation induction. Both batches confirmed to be effective to treat and prevent ocular inflammation.
This paper references
Determination of eye irritation potential of low-irritant products: comparison of in vitro results with the in vivo draize rabbit test
Andrea Martins da Nobrega (2012)
Influence of Preparation Conditions on Acyclovir-Loaded Poly-d,l-Lactic Acid Nanospheres and Effect of PEG Coating on Ocular Drug Bioavailability
C. Giannavola (2004)
Role of hydroxypropyl-β-cyclodextrin on freeze-dried and gamma-irradiated PLGA and PLGA–PEG diblock copolymer nanospheres for ophthalmic flurbiprofen delivery
E. Vega (2012)
INVITTOX: The ERGATT/FRAME data bank of in vitro techniques in toxicology.
M. Warren (1990)
Enhanced Ocular Anti-Inflammatory Activity of Ibuprofen Carried by an Eudragit RS100® Nanoparticle Suspension
C. Bucolo (2002)
Cationic solid lipid nanoparticles interfere with the activity of antioxidant enzymes in hepatocellular carcinoma cells.
S. Doktorovová (2014)
Overview on Clinical Data of Dexibuprofen
W. Phleps (2013)
Effect of polymer viscosity on physicochemical properties and ocular tolerance of FB-loaded PLGA nanospheres.
J. Araújo (2009)
Effect of mucoadhesive polymers on the in vitro performance of insulin-loaded silica nanoparticles: Interactions with mucin and biomembrane models.
T. Andreani (2015)
Feasibility of Lipid Nanoparticles for Ocular Delivery of Anti-Inflammatory Drugs
E. Souto (2010)
Dexibuprofen (S(+)-Isomer Ibuprofen) Reduces Gastric Damage and Improves Analgesic and Antiinflammatory Effects in Rodents
A. Bonabello (2003)
Improved and safe transcorneal delivery of flurbiprofen by NLC and NLC-based hydrogels.
E. Gonzalez-Mira (2012)
Enhanced brain targeting by synthesis of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine and incorporation into solid lipid nanoparticles.
J. X. Wang (2002)
Ocular drug delivery: a clue from nanotechnology
C. Bucolo (2012)
Clinical Pharmacokinetics of Ibuprofen
N. M. Davies (1998)
Probing the interaction of nanoparticles with mucin for drug delivery applications using dynamic light scattering.
P. Griffiths (2015)
Ocular pharmacoscintigraphic and aqueous humoral drug availability of ganciclovir-loaded mucoadhesive nanoparticles in rabbits
Sohail Akhter (2013)
Doxorubicin-loaded micelles based on multiarm star-shaped PLGA–PEG block copolymers: influence of arm numbers on drug delivery
Guilei Ma (2015)
Development of oral Sustained release dosage form for low melting chiral compound Dexibuprofen and it’s in virto-in vivo evaluation
Muralidharan Selvadurai (2011)
High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.
D. Cun (2011)
Design of cationic lipid nanoparticles for ocular delivery: development, characterization and cytotoxicity.
J. Fangueiro (2014)
Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study.
F. Silverstein (2000)
Biodegradation and biocompatibility of PLA and PLGA microspheres
J. Anderson (1997)
The hen's egg chorioallantoic membrane (HET-CAM) test to predict the ophthalmic irritation potential of a cysteamine-containing gel: Quantification using Photoshop® and ImageJ.
Barbara McKenzie (2015)
Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration.
G. Abrego (2015)
Eye irritation hazard of chemicals and formulations assessed by methods in vitro.
D. Jírová (2014)
The use of mucoadhesive polymers in ocular drug delivery.
A. Ludwig (2005)
The Validation of a Functional, Isolated Pig Bladder Model for Physiological Experimentation
B. Parsons (2012)
Modeling and comparison of dissolution profiles.
P. Costa (2001)
Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery
Aimee Vasconcelos (2015)
Polylactic-co-glycolic acid mesh coated with fibrin or collagen and biological adhesive substance as a prefabricated, degradable, biocompatible, and functional scaffold for regeneration of the urinary bladder wall.
S. A. Salem (2013)
Development and characterization of folate anchored Saquinavir entrapped PLGA nanoparticles for anti-tumor activity
R. Singh (2015)
Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen.
G. Abrego (2014)
Polymeric nanoparticles augment the ocular hypotensive effect of melatonin in rabbits.
T. Musumeci (2013)
Enhancement of solubility of dexibuprofen applying mixed hydrotropic solubilization technique.
B. M. El-Houssieny (2014)
Flurbiprofen PLGA-PEG nanospheres: role of hydroxy-β-cyclodextrin on ex vivo human skin permeation and in vivo topical anti-inflammatory efficacy.
E. Vega (2013)
Comparison of safety, efficacy and tolerability of Dexibuprofen and Ibuprofen in the treatment of osteoarthritis of the hip or knee
O. Zamani (2014)
Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone.
Maribel Teixeira (2005)
Polymeric nanoparticulate system: a potential approach for ocular drug delivery.
R. C. Nagarwal (2009)
Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats.
N. Khalil (2013)
α(V)β(3) integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug.
Nora Graf (2012)
Mechanism of drug release from poly(L-lactic acid) matrix containing acidic or neutral drugs.
M. Miyajima (1999)
Reaction kinetics of dual setting α-tricalcium phosphate cements
K. Hurle (2015)
Factors affecting the degradation and drug-release mechanism of poly(lactic acid) and poly[(lactic acid)-co-(glycolic acid)]
F. Alexis (2005)
PLGA nanospheres for the ocular delivery of flurbiprofen: drug release and interactions.
E. Vega (2008)
Dexibuprofen: pharmacology, therapeutic uses and safety
S. Kaehler (2004)
Eudragit RS100 nanosuspensions for the ophthalmic controlled delivery of ibuprofen.
R. Pignatello (2002)
This paper is referenced by
Development of Halobetasol-loaded nanostructured lipid carrier for dermal administration: Optimization, physicochemical and biopharmaceutical behavior, and therapeutic efficacy.
Paulina Carvajal-Vidal (2019)
PEGylated microemulsion for dexamethasone delivery to posterior segment of eye
K. Nayak (2020)
Construction of poly (vinyl alcohol)/poly (lactide-glycolide acid)/vancomycin nanoparticles on titanium for enhancing the surface self-antibacterial activity and cytocompatibility.
Zehui Liu (2017)
Estudio de formulaciones de ketorolaco de trometamina para aplicación sobre mucosas y piel
Mireia Mallandrich Miret (2017)
Quality-by-design model in optimization of PEG-PLGA nano micelles for targeted cancer therapy
Zahra Eskandari (2018)
In-situ forming gels containing fluorometholone-loaded polymeric nanoparticles for ocular inflammatory conditions.
Roberto González-Pizarro (2019)
Epigallocatechin-3-gallate loaded PEGylated-PLGA nanoparticles: A new anti-seizure strategy for temporal lobe epilepsy.
A. Cano (2018)
Development of Pranoprofen Loaded Nanostructured Lipid Carriers to Improve Its Release and Therapeutic Efficacy in Skin Inflammatory Disorders
M. Rincón (2018)
Quality-ByDesign Model in Optimization of PEG-PLGA Nano Micelles for Targeted Cancer Therapy
Z. Eskandari (2018)
Polymeric Nanoparticles: Production, Characterization, Toxicology and Ecotoxicology
A. Zielińska (2020)
Nanomedicine for the effective and safe delivery of non-steroidal anti-inflammatory drugs: a review of preclinical research.
H. Al-Lawati (2019)
Formulating octyl methoxycinnamate in hybrid lipid-silica nanoparticles: An innovative approach for UV skin protection
T. Andreani (2020)
Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide
E. Sánchez-López (2020)
Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study
E. Sánchez-López (2020)
Retinal Drug Delivery: Rethinking Outcomes for the Efficient Replication of Retinal Behavior
E. Souto (2020)
Tailored nanostructured platforms for boosting transcorneal permeation: Box–Behnken statistical optimization, comprehensive in vitro, ex vivo and in vivo characterization
Ibrahim Elsayed (2017)
Mildly Cross-Linked Dendrimer Hydrogel Prepared via Aza-Michael Addition Reaction for Topical Brimonidine Delivery.
J. Wang (2017)
Novel nanosystems for the treatment of ocular inflammation: Current paradigms and future research directions
Lida Lalu (2017)
Development, Cytotoxicity and Eye Irritation Profile of a New Sunscreen Formulation Based on Benzophenone-3-poly(ε-caprolactone) Nanocapsules
T. Barbosa (2019)
Novel chitosan-based pH-responsive lipid-polymer hybrid nanovesicles (OLA-LPHVs) for delivery of vancomycin against methicillin-resistant Staphylococcus aureus infections.
D. Hassan (2020)
Eplerenone nanoemulsions for treatment of hypertension. Part I: Experimental design for optimization of formulations and physical characterization
S. Özdemir (2018)
Advanced Formulation Approaches for Ocular Drug Delivery: State-Of-The-Art and Recent Patents
E. B. Souto (2019)
Design of experiments (DoE) in pharmaceutical development
Stavros N Politis (2017)
Lipid nanoparticles as carriers for the treatment of neurodegeneration associated with Alzheimer's disease and glaucoma: present and future challenges.
Elena H. Sánchez López (2020)
New potential strategies for Alzheimer's disease prevention: pegylated biodegradable dexibuprofen nanospheres administration to APPswe/PS1dE9.
E. Sánchez-López (2017)
Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders
Marcelle Silva-Abreu (2017)
Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation
R. Mazet (2020)
Nanopharmaceutics: Part II—Production Scales and Clinically Compliant Production Methods
E. B. Souto (2020)
Recent advance of nanoparticle-based topical drug delivery to the posterior segment of the eye
Y. Wang (2018)
Periocular injection of candesartan-PLGA microparticles inhibits laser-induced experimental choroidal neovascularization
Yoshitaka Okuda (2019)
Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery
Tingting Xu (2018)
Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways
M. Ettcheto (2017)See more