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.

In situforming poly(lactic acid-co-glycolic acid) implants containing leuprolide acetate/β-cyclodextrin complexes: preparation, characterization, andin vitrodrug release

“…LA degradation pathways are generally classified into hydrolysis, aggregation, D,Lisomerization and oxidation [18]. This degradation can disrupt the LA concentration within PLGA implant, since increasing the acidity within PLGA matrix during release period [19,20] can accelerate the degradation of reserved LA before release [21]. Similar phenomenon has been previously observed for vinca alkaloids encapsulated in PLGA implant [22].…”

“…In our previous work [21], we prepared LA/β-CD complexes to improve the aqueous stability of LA in acidic media. In this study, the formed complexes were used to prepare It has been shown that the use of relatively hydrophilic PLGA carrying free carboxylic end groups resulted in a significantly higher drug encapsulation efficiency compared to end-capped PLGA [29,30].…”

“…Complexes of LA with different portions of β-CD were prepared through freeze-drying method [21]. Briefly, 50 mg of LA and different quantities of β-CD (50, 250 and 500 mg) were added in 20 mL of PBS medium and mixed at 37 °C for 1 hour using a magnetic stirrer.…”

“…In our previous work [21], we improved the aqueous stability of LA in acidic media through complexation with β-CD. In the present study, the formed complexes were used to prepare PLGA-based ISIs for LA delivery.…”

Development of novel PLGA nanoparticles with co‐encapsulation of docetaxel and abiraterone acetate for a highly efficient delivery into tumor cells

“…This observation allows us to confirm the assertion that the release of the drugs proceeds at the initial ratio of the components (1:3), that is, providing the necessary ratio to achieve maximum therapeutic effect. The values of the release exponent n (<0.45) in the K–P model indicate that the release of substances from the polymeric forms proceeds according to the Fick diffusion mechanism …”