Transport properties of hydrophilic compounds in PLGA microspheres

Abstract

Biodegradable polyesters, such as the poly(lactic-co-glycolic acid) (PLGA), have been extensively used as a polymer matrix for entrapping a variety of active compounds. In this study, the physicochemical phenomena that control the mass transport mechanism of hydrophilic compounds released from PLGA microspheres were identified. This study aims to produce and characterize PLGA microspheres loaded with metformin hydrochloride (MH) and perform a case study using the literature data of PLGA microspheres loaded with fluorescein isothiocyanate-dextran (FITC-dextran). The MH is a low molecular weight compound that was easily and rapidly transported by diffusion mechanism through the microsphere pores. The FITC-dextran, as a high molecular weight compound, depended on the mechanism of polymer erosion and mesopore formation, with 18 days of duration, before its release by diffusion mass transfer. Values of the effective diffusion coefficient of MH and FITC-dextran, both in PLGA, were 2.4 x 10-13 and 5.3 x 10-18 m2 s-1, respectively, with a difference of five orders of magnitude attributed to the molecular weight of these hydrophilic compounds and the main mass transport that governed their release. This study provides important insights into the mechanisms of mass transfer and their correlation with the physicochemical properties of both hydrophilic compounds and the PLGA matrix, contributing to the development of biodegradable controlled delivery systems for a variety of applications in chemical, biotechnological, and pharmaceutical industries.

Diffusion of curcumin in PLGA-based carriers for drug delivery: a molecular dynamics study

“…3 c and f show that the D of curcumin through the hydrated PLGA is significantly lower as compared with that of curcumin in water alone, because of the enhanced diffusion resistance induced by PLGA chains. The obtained curcumin diffusion coefficients lie in a range between m 2 /s (configuration 5, DOE1) and m 2 /s (configuration 2, DOE2), obtaining comparable values with respect to previous results in the literature analyzing similar — but not identical — setups [ 58 , 68 – 70 ]. In detail, Samanta and Roccatano [ 68 ] performed MD simulations of curcumin and pluronic block copolymer in different liquid environments, observing a value of diffusion coefficient of curcumin as low as m 2 /s.…”

“…This value lies in our range, confirming the routine adopted and the reliability of the results obtained. Furthermore, Burin and colleagues [ 70 ] showed effective diffusion coefficients of molecules — with comparable molecular weight with respect to curcumin — through PLGA in the order of m 2 /s.…”