Role of hydroxypropyl-β-cyclodextrin on freeze-dried and gamma-irradiated PLGA and PLGA–PEG diblock copolymer nanospheres for ophthalmic flurbiprofen delivery

Poly(D,L-lactide-co-glycolide) and poly(D,L-lactide-co-glycolide) with poly(ethylene glycol) nanospheres (NSs) incorporating flurbiprofen (FB) were freeze-dried with several cryoprotective agents and sterilized by γ-irradiation. Only when 5.0% (w/v) hydroxypropyl-β-cyclodextrin (HPβCD) was used, a complete resuspension by manual shaking and almost identical particle size of the NSs was obtained after freeze-drying. In vitro drug release and ex vivo corneal permeation of NSs with and without HPβCD were evaluated. The presence of HPβCD resulted in a reduction of burst effect, providing a more sustained release of the drug. A significant decrease in the FB transcorneal permeation of NSs containing HPβCD was obtained, related to the slower diffusion of FB observed in the in vitro results. The uptake mechanism of the NSs was examined by confocal microscopy, suggesting that NSs penetrate corneal epithelium through a transcellular pathway. Ocular tolerance was assessed in vitro and in vivo by the Eytex™ and Draize test, respectively. Long-term stability studies revealed that γ-irradiated NSs stored as freeze-dried powders maintained their initial characteristics. Stability studies of the resuspended NSs after 3 months of storage in the aqueous form showed that NSs were stable at 4°C, while formulations stored at 25°C and 40°C increased their initial particle size.

• Publication year

  2012

• Venue

  International Journal of Nanomedicine

• Publication date

  2012-03-09

• Fields of study

  Medicine, Materials Science

• Identifiers
  DOI 10.2147/IJN.S28481PMID 22457594PMCID 3310410
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Sustained Release and Permeation of Timolol from Surface-Modified Solid Lipid Nanoparticles through Bioengineered Human Cornea

  2009cited by this paper
• Nanomedicines for ocular NSAIDs: safety on drug delivery.

  2009cited by this paper
• An ion pairing approach to increase the loading of hydrophilic and lipophilic drugs into PEGylated PLGA nanoparticles.

  2009cited by this paper
• Application of the 3Rs Principles for Animals Used for Experiments at the Beginning of the 21st Century

  2008cited by this paper
• PLGA nanospheres for the ocular delivery of flurbiprofen: drug release and interactions.

  2008cited by this paper
• Freeze-drying of nanoparticles: formulation, process and storage considerations.

  2006cited by this paper
• Lyoprotected nanosphere formulations for paclitaxel controlled delivery.

  2006cited by this paper
• A pilot study of freeze drying of poly(epsilon-caprolactone) nanocapsules stabilized by poly(vinyl alcohol): formulation and process optimization.

  2006cited by this paper
• Plasticization of poly(L-lactide) with poly(propylene glycol).

  2006cited by this paper
• Flurbiprofen loaded biodegradable nanoparticles for ophtalmic administration.

  2006influential reference
• How cyclodextrin incorporation affects the properties of protein-loaded PLGA-based microspheres: the case of insulin/hydroxypropyl-beta-cyclodextrin system.

  2005cited by this paper
• The Characteristics and Mechanisms of Uptake of PLGA Nanoparticles in Rabbit Conjunctival Epithelial Cell Layers

  2004cited by this paper
• The influence of the use of viscosifying agents as dispersion media on the drug release properties from PLGA nanoparticles.

  2004cited by this paper
• Influence of Preparation Conditions on Acyclovir-Loaded Poly-d,l-Lactic Acid Nanospheres and Effect of PEG Coating on Ocular Drug Bioavailability

  2003cited by this paper
• The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa.

  2003cited by this paper
• Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir.

  2001cited by this paper
• Acyclovir-containing liposomes for potential ocular delivery. Corneal penetration and absorption.

  2000cited by this paper
• Freeze-drying of polycaprolactone and poly(D,L-lactic-glycolic) nanoparticles induce minor particle size changes affecting the oral pharmacokinetics of loaded drugs.

  2000cited by this paper
• Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems.

  2000cited by this paper
• Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid polymers: I. Synthesis and characterization

  2000cited by this paper
• Tetracycline-HCl-loaded poly(DL-lactide-co-glycolide) microspheres prepared by a spray drying technique: influence of gamma-irradiation on radical formation and polymer degradation.

  1999cited by this paper
• Flurbiprofen, S(+), eyedrops: formulation, enantiomeric assay, shelf-life and pharmacology.

  1999cited by this paper
• Flurbiprofen, S(+), eyedrops: formulation, enantiomeric assay, shelflife and pharmacology

  1999cited by this paper
• PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug.

  1999cited by this paper
• Gamma irradiation effects on poly(DL-lactictide-co-glycolide) microspheres.

  1998cited by this paper
• Influence of the stabilizer coating layer on the purification and freeze-drying of poly(D,L-lactic acid) nanoparticles prepared by an emulsion-diffusion technique.

  1998cited by this paper
• Combined Poly(isobutylcyanoacrylate) and Cyclodextrins Nanoparticles for Enhancing the Encapsulation of Lipophilic Drugs

  1998cited by this paper
• Influence of the stabilizer coating layer on the purification and freeze-drying of poly(D,L-lactic acid) nanoparticles prepared by an emulsion-diffusion technique

  1998cited by this paper
• Sequential Staining: The Effects of Sodium Fluorescein, Osmolarity, and pH on Human Corneal Epithelium

  1997cited by this paper
• Determination of dexamethasone in tears by capillary electrophoresis.

  1997cited by this paper
• Biodegradation and biocompatibility of PLA and PLGA microspheres.

  1997cited by this paper
• Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid oligomers: I. Synthesis and characterization.

  1997cited by this paper
• Influence of Irradiation Sterilization on Polymers Used as Drug Carriers—A Review

  1997cited by this paper
• Gamma irradiation effects of poly(D,L-lactide-co-glycolide) microspheres

  1996cited by this paper
• Rifampicin Carrying Poly (D, L‐Lactide)/Poly(Ethylene Glycol) Microspheres: Loading and Release

  1996cited by this paper
• Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers.

  1996cited by this paper
• Rifampicin carrying poly (D,L-lactide)/poly(ethylene glycol) microspheres: loading and release.

  1996cited by this paper
• Gamma Irradiation Effects on Molecular Weight and in Vitro Degradation of Poly(D,L-Lactide-CO-Glycolide) Microparticles

  1995cited by this paper
• The effect of γ-irradiation on drug release from poly(lactide) microspheres

  1995cited by this paper
• Ocular drug delivery conventional ocular formulations

  1995cited by this paper
• Thermoanalysis of microspheres

  1995cited by this paper
• Acceptance of in vitro studies by regulatory authorities.

  1994cited by this paper
• Study of the mechanism of interaction of poly(ϵ-caprolactone) nanocapsules with the cornea by confocal laser scanning microscopy

  1994cited by this paper
• Surface modification of i.v. injectable biodegradable nanoparticles with poloxamer polymers and poloxamine 908

  1993cited by this paper
• Biodegradable pseudolatexes: the chemical stability of poly(D,L-lactide) and poly(epsilon-caprolactone) nanoparticles in aqueous media.

  1992cited by this paper
• Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic responses.

  1992cited by this paper
• Biodegradable Pseudolatexes: The Chemical Stability of Poly(D,L-Lactide) and Poly (ε-Caprolactone) Nanoparticles in Aqueous Media

  1992cited by this paper
• Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic responses.

  1992cited by this paper
• An in vitro method for estimating ocular irritation.

  1990cited by this paper
• Drug release from submicronized o/w emulsion: a new in vitro kinetic evaluation model

  1990cited by this paper
• Controlled release of bioactive agents from lactide/glycolide polymers

  1990cited by this paper
• Nanocapsule formation by interfacial polymer deposition following solvent displacement

  1989cited by this paper
• Ocular disposition of poly-hexyl-2-cyano[3-14C]acrylate nanoparticles in the albino rabbit

  1985cited by this paper
• Analysis of Fickian and non-Fickian drug release from polymers.

  1985cited by this paper
• Determination of ibuprofen in capillary and venous plasma by high-performance liquid chromatography with ultraviolet detection.

  1984cited by this paper
• Corneal penetration behavior of beta-blocking agents I: Physiochemical factors.

  1983cited by this paper
• Mechanisms of potassium chloride release from compressed, hydrophilic, polymeric matrices: effect of entrapped air.

  1983cited by this paper
• Corneal Penetration Behavior of β-Blocking Agents I: Physicochemical Factors

  1983cited by this paper
• Mechanisms of solute release from porous hydrophilic polymers

  1983cited by this paper
• Effect of particle size on ophthalmic bioavailability of dexamethasone suspensions in rabbits.

  1980cited by this paper
• Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits.

  1979cited by this paper
• [Irritant power of the principle chlorinated aliphatic solvents on the skin and ocular mucosa of the rabbit].

  1976cited by this paper
• Clinical Ophthalmology Dovepress

  year unknowncited by this paper
• International Journal of Nanomedicine

  year unknowncited by this paper

• Novel Tissue-Specific Multifunctionalized Nanotechnological Platform Encapsulating Riluzole Against Motor Neuron Diseases

  2025cites this paper
• In vitro, in vivo and in silico assessment of bioresorbable PLGA-PEG-PLGA based thermosensitive hydrogel mediated 30-days delivery of Lurasidone HCl for schizophrenia.

  2025cites this paper
• Redefining cyclodextrin-based systems: A multiscale framework of structure, function and application interconnection

  2025cites this paper
• Advances in Chitosan Derivatives: Preparation, Properties and Applications in Pharmacy and Medicine

  2024cites this paper
• Design of an oral formulation combining PVA nanofibers and PEGylated liposomes for enhanced drug delivery1

  2024cites this paper
• Anti-angiogenic activity of polymeric nanoparticles loaded with ursolic acid

  2024influential citation
• Rescuing a Troubled Tolcapone with PEGylated PLGA Nanoparticles: Design, Characterization, and Hepatotoxicity Evaluation.

  2024cites this paper
• Poly(lactic-co-glycolic acid) nanoparticle fabrication, functionalization, and biological considerations for drug delivery

  2024cites this paper
• Cyclodextrins-block copolymer drug delivery systems: From design and development to preclinical studies

  2024cites this paper
• Investigating the prilling/vibration technique to produce gastric-directed drug delivery systems for misoprostol.

  2024cites this paper
• Development of Lyophilised Eudragit® Retard Nanoparticles for the Sustained Release of Clozapine via Intranasal Administration

  2023cites this paper
• Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies

  2023cites this paper
• Optimization of the different phases of the freeze-drying process of solid lipid nanoparticles using experimental designs.

  2023cites this paper
• Cyclodextrin-based nanogel of flurbiprofen for dermal application: In vitro studies and in vivo skin irritation evaluation

  2023cites this paper
• LipoParticles: a lipid membrane coating onto polymer particles to enhance the internalization in osteoblast cells.

  2023cites this paper
• Cyclodextrin modified with different groups to enhance the drug delivery efficiency of gold nanoparticles to treat cancer

  2023cites this paper
• Sustainability in Drug and Nanoparticle Processing.

  2023cites this paper
• Precision Medicines for Retinal Lipid Metabolism-Related Pathologies

  2023cites this paper
• Biodegradable Nanoparticles Loaded with Levodopa and Curcumin for Treatment of Parkinson’s Disease

  2022cites this paper
• Development of Peptide Targeted PLGA-PEGylated Nanoparticles Loading Licochalcone-A for Ocular Inflammation

  2022cites this paper
• Cyclodextrin Stabilized Freeze-Dried Silica/Chitosan Nanoparticles for Improved Terconazole Ocular Bioavailability

  2022cites this paper
• Enhanced Bioavailability & higher Uptake of Brain-targeted Surface Engineered Delivery System of Naringenin developed as a therapeutic for Autism Spectrum Disorder.

  2022cites this paper
• Host-Guest Interaction of Anti-Carcinogenic Drug Zoledronic Acid with β-Cyclodextrin in Solid and Solution Forms

  2022cites this paper
• Polymeric Nanoparticles in Hybrid Catalytic Processing and Drug Delivery System

  2022cites this paper
• Customized cationic nanoemulsions loading triamcinolone acetonide for corneal neovascularization secondary to inflammatory processes.

  2022cites this paper
• Liquiritin-hydroxypropyl-beta-cyclodextrin inclusion complex: preparation, characterization, bioavailability and antitumor activity evaluation.

  2022cites this paper
• Sustainable preparation of anti-inflammatory atorvastatin PLGA nanoparticles.

  2021cites this paper
• Development of topical eye-drops of lactoferrin-loaded biodegradable nanoparticles for the treatment of anterior segment inflammatory processes.

  2021cites this paper
• Nanotechnology based ocular drug delivery system : A Review

  2021cites this paper
• Formulation and In Vitro Characterization of PLGA/PLGA-PEG Nanoparticles Loaded with Murine Granulocyte-Macrophage Colony-Stimulating Factor

  2021cites this paper
• Correlating Super-Resolution Microscopy and Transmission Electron Microscopy Reveals Multiparametric Heterogeneity in Nanoparticles

  2021cites this paper
• Biodistribution and efficacy of the anticancer drug, oxaliplatin palmitate acetate, in mice.

  2021cites this paper
• Dexibuprofen Therapeutic Advances: Prodrugs and Nanotechnological Formulations

  2021cites this paper
• Lipo-PEG nano-ocular formulation successfully encapsulates hydrophilic fluconazole and traverses corneal and non-corneal path to reach posterior eye segment

  2021cites this paper
• Transformation of nanoparticles into compacts: a study on PLGA and celecoxib nanoparticles.

  2021cites this paper
• Quantifying the effect of PEG architecture on nanoparticle ligand availability using DNA-PAINT

  2021cites this paper
• Stabilization by Nano Spray Dryer of Pioglitazone Polymeric Nanosystems: Development, In Vivo, Ex Vivo and Synchrotron Analysis

  2021influential citation
• Difluprednate-Hydroxypropyl-β-Cyclodextrin-Based Ophthalmic Solution for Improved Delivery in a Porcine Eye Model

  2021cites this paper
• Skin permeability and transdermal delivery route of 30-nm cyclosporin A-loaded nanoparticles using PLGA-PEG-PLGA triblock copolymer

  2020cites this paper
• Recent Advances in Host–Guest Self‐Assembled Cyclodextrin Carriers: Implications for Responsive Drug Delivery and Biomedical Engineering

  2020cites this paper
• Fast disintegrating tablet of Doxazosin Mesylate nanosuspension: Preparation and characterization

  2020cites this paper
• Characterisation of 2-HP-β-cyclodextrin-PLGA nanoparticle complexes for potential use as ocular drug delivery vehicles

  2019cites this paper
• Bioinspired Nanocomposites: Applications In Disease Diagnosis And Treatment.

  2019cites this paper
• Topical and Transdermal Delivery with Chemical Enhancers and Nanoparticles

  2019cites this paper
• Gemcitabine and betulinic acid co-encapsulated PLGA-PEG polymer nanoparticles for improved efficacy of cancer chemotherapy.

  2019cites this paper
• Quality-ByDesign Model in Optimization of PEG-PLGA Nano Micelles for Targeted Cancer Therapy

  2018cites this paper
• Insights into maleimide‐thiol conjugation chemistry: Conditions for efficient surface functionalization of nanoparticles for receptor targeting

  2018cites this paper
• Memantine loaded PLGA PEGylated nanoparticles for Alzheimer’s disease: in vitro and in vivo characterization

  2018cites this paper
• Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders

  2018cites this paper
• Memantine-Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma.

  2018cites this paper
• Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles.

  2018cites this paper
• Quality-by-design model in optimization of PEG-PLGA nano micelles for targeted cancer therapy

  2018cites this paper
• A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride

  2017cites this paper
• Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics.

  2017cites this paper
• Polyethylene Glycol-Poly-Lactide-co-Glycolide Block Copolymer-Based Nanoparticles as a Potential Tool for Off-Label Use of N-Acetylcysteine in the Treatment of Diastrophic Dysplasia.

  2017cites this paper
• PLGA-PEG nanoparticles as potential tool for off-label use of N-acetylcysteine in the treatment of diastrophic dysplasia

  2017cites this paper
• Preparation, characterization, and in vitro anti-inflammatory evaluation of novel water soluble kamebakaurin/hydroxypropyl-β-cyclodextrin inclusion complex

  2017cites this paper
• Novel approaches for effective design of controlled drug release systems, employing hybrid semi-parametric mathematical systems

  2017influential citation
• Optimización del proceso de liofilización de sistemas nanoestructurados de flurbiprofeno para uso oftálmico y su influencia en el comportamiento biofarmacéutico

  2017cites this paper
• Targeted drug distribution in tumor extracellular fluid of GD2‐expressing neuroblastoma patient‐derived xenografts using SN‐38‐loaded nanoparticles conjugated to the monoclonal antibody 3F8

  2017cites this paper
• Preparation of Drug-Loaded PLGA-PEG Nanoparticles by Membrane-Assisted Nanoprecipitation

  2017cites this paper
• Influence of freeze-drying and γ-irradiation in preclinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using d-(+)-trehalose and polyethylene glycol

  2016cites this paper
• Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment

  2016cites this paper
• Development of a topical ocular drug delivery system using polymeric nanoparticles

  2016cites this paper
• Formulation, characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment

  2016cites this paper
• Nano-Biomaterials For Ophthalmic Drug Delivery

  2016cites this paper
• PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen-in vitro, ex vivo and in vivo characterization.

  2016cites this paper
• Ex vivo permeation of carprofen from nanoparticles: A comprehensive study through human, porcine and bovine skin as anti-inflammatory agent.

  2016cites this paper
• Nanotechnology-based strategies for treatment of ocular disease

  2016cites this paper
• Prolonged Ocular Retention of Mucoadhesive Nanoparticle Eye Drop Formulation Enables Treatment of Eye Diseases Using Significantly Reduced Dosage.

  2016cites this paper
• Preparation, characterization, and pharmacokinetics study of capsaicin via hydroxypropyl-beta-cyclodextrin encapsulation

  2016cites this paper
• Influence of freeze-drying and γ-irradiation in preclinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using d-(+)-trehalose and polyethylene glycol.

  2016cites this paper
• Study of stability and biophysical characterization of ranibizumab and aflibercept.

  2016cites this paper
• Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

  2015cites this paper
• Mucoadhesive Polymers for Enhancing Retention in Ocular Drug Delivery

  2015cites this paper
• Diseño y síntesis de nanosistemas derivatizados con péptidos y su aplicación en biomedicina

  2015cites this paper
• Recent trends in preparation of poly(lactide- co -glycolide) nanoparticles by mixing polymeric organic solution with antisolvent

  2015cites this paper
• Polymeric Nanoparticles Based Topical Drug Delivery: An Overview

  2015cites this paper
• Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: Ocular anti-inflammatory applications.

  2015cites this paper
• Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentallyinduced dry eye syndrome

  2015cites this paper
• Intranasal and intravenous administration of octa‐arginine modified poly(lactic‐co‐glycolic acid) nanoparticles facilitates central nervous system delivery of loperamide

  2015cites this paper
• Development and characterization of two nano-structured systems for topical application of flavanones isolated from Eysenhardtia platycarpa.

  2014cites this paper
• Carbohydrate based nanoparticles for drug delivery across biological barriers.

  2014cites this paper
• Propulsive PAT paradigm: Optimization of Freeze Drying Process

  2014cites this paper
• Nanoparticulate Transscleral Ocular Drug Delivery

  2014cites this paper
• Improvement in autologous human fat transplant survival with SVF plus VEGF–PLA nano‐sustained release microspheres

  2014cites this paper
• Memantine Loaded Biodegradable Polymeric Nanoparticles for Glaucoma Treatment

  2014cites this paper
• Evaluation of the Pharmacokinetics and Ocular Tolerance of a Microemulsion Containing Tacrolimus

  2014cites this paper
• Physical stabilization of low-molecular-weight amorphous drugs in the solid state: a material science approach.

  2014cites this paper
• Stealth Amphotericin B nanoparticles for oral drug delivery: In vitro optimization

  2014cites this paper
• Enhanced bioavailability of orally administered flurbiprofen by combined use of hydroxypropyl-cyclodextrin and poly(alkyl-cyanoacrylate) nanoparticles

  2013cites this paper
• BMP 7 Gene Transfer via Gold Nanoparticles into Stroma Inhibits Corneal Fibrosis In Vivo Citation

  2013cites this paper
• Innovative formulations for the controlled and site-specific delivery of antiinflammatory drugs.

  2013cites this paper
• Flurbiprofen PLGA-PEG nanospheres: role of hydroxy-β-cyclodextrin on ex vivo human skin permeation and in vivo topical anti-inflammatory efficacy.

  2013cites this paper
• BMP7 Gene Transfer via Gold Nanoparticles into Stroma Inhibits Corneal Fibrosis In Vivo

  2013cites this paper
• Comparative evaluation of the degree of pegylation of poly(lactic‐co‐glycolic acid) nanoparticles in enhancing central nervous system delivery of loperamide

  2013influential citation
• Cyclodextrin as membrane protectant in spray-drying and freeze-drying of PEGylated liposomes.

  2012cites this paper