title: In situ-forming PLGA implants loaded with leuprolide acetate/β-cyclodextrin complexes: mathematical modelling and degradation.
abstract: Drug release mechanism of in situ-forming implants (ISIs) based on poly(lactic acid-co-glycolic acid) (PLGA) loaded with leuprolide acetate/β-cyclodextrin (LA/β-CD) complexes via fitting with four diffusion-based semi-empirical models were studied. The release rate constants and release exponent of ISIs were calculated. The main drug release mechanism was Fickian diffusion. The LA diffusion coefficient and release constant were decreased via increasing the portion of β-CD in complexes. The release curve was parabolic, with a higher initial slope and then consistent with the exponential. All ISIs containing LA/β-CD complexes better fitted with the Korsmeyer-Peppas, Weibull and Peppas-Sahlin models rather than first-order model. Furthermore, the effect of LA/β-CD complexation on the degradation of ISIs was studied through scanning electron microscopy (SEM). Results showed that hydrophilic nature of β-CD facilitated the surface erosion of PLGA chains, however after 18 d, ISI-1/10 had still a proper structural strength, due to no hydrolytic degradation of β-CD in this implant.
authors.affiliation: a Department of Biomedical Engineering, Science and Research Branch , Islamic Azad University , Tehran , Iran ;
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rahimi
authors.affiliation: b Department of Novel Drug Delivery Systems , Iran Polymer and Petrochemical Institute , Tehran , Iran ;
authors.forename: Hamid
authors.initials: H
authors.lastname: Mobedi
authors.affiliation: c Biomaterials Group , Materials and Energy Research Center , Tehran , Iran.
authors.forename: Aliasghar
authors.initials: A
authors.lastname: Behnamghader
mesh_terms: D004343:Drug Implants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016729:Leuprolide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008956:Models, Chemical; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004343:Drug Implants; D047392:beta-Cyclodextrins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016729:Leuprolide
keywords: In situ-forming implant; PLGA; degradation; leuprolide acetate/β-cyclodextrin complexes; mathematical modelling