title: Comparative evaluation of cyclosporine A/HPβCD-incorporated PLGA nanoparticles for development of effective ocular preparations.
abstract: To improve poor water solubility of cyclosporine A (CsA), hydroxypropyl-beta-cyclodextrin (HPβCD) was incorporated into the nanoparticle formulation. Solid complexes of CsA with HPβCD in different ratios were prepared by the kneading method. CsA containing alone or in combination with HPβCD in poly-lactide-co-glycolide (P-CsA or P-CsA-HPβCD) nanoparticles were prepared by the emulsification solvent evaporation method. The mean size of CsA-loaded NPs was found to be approximately 220 nm. The solubility of CsA was significantly improved and the phase solubility diagram of CsA-HPβCD systems showed an A(L) type phase. Nanoparticles showed high CsA encapsulation efficiency (88%) and production yield (89%). Release rate was increased by the presence of HPβCD and total cumulative release ranged from 75% to 96% in 24 h. In vitro cytotoxicity study assay resulted in a low toxicity for all types of nanoparticles. After 6 h incubation period, the cellular uptake was found at 33% and 32% for P-CsA and P-HPβCD-CsA nanoparticles, respectively.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Technology, Hacettepe University, 06100 Ankara, Turkey. pelinaks@yahoo.com
authors.forename: Pelin
authors.initials: P
authors.lastname: Aksungur
authors.forename: Murat
authors.initials: M
authors.lastname: Demirbilek
authors.forename: Emir B
authors.initials: EB
authors.lastname: Denkbaş
authors.forename: Nurşen
authors.initials: N
authors.lastname: Unlü
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D002460:Cell Line; D003505:Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016572:Cyclosporine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility
chemical_list: D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine