Preparation, characterization and in vitro release study of BSA-loaded double-walled glucose-poly(lactide-co-glycolide) microspheres

Abstract

The aim of this study was to prepare a model protein, bovine serum albumin (BSA) loaded double-walled microspheres using a fast degrading glucose core, hydroxyl-terminated poly(lactide-co-glycolide) (Glu-PLGA) and a moderate-degrading carboxyl-terminated PLGA polymers to reduce the initial burst release and to eliminate the lag phase from the release profile of PLGA microspheres. The double-walled microspheres were prepared using a modified water-in-oil-in-oil-in-water (w/o/o/w) method and single-polymer microspheres were prepared using a conventional water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The particle size, morphology, encapsulation efficiency, thermal properties, in vitro drug release and structural integrity of BSA were evaluated in this study. Double-walled microspheres prepared with Glu-PLGA and PLGA polymers with a mass ratio of 1:1 were non-porous, smooth-surfaced, and spherical in shape. A significant reduction of initial burst release was achieved for the double-walled microspheres compared to single-polymer microspheres. In addition, microspheres prepared using Glu-PLGA and PLGA polymers in a mass ratio of 1:1 exhibited continuous BSA release after the small initial burst without any lag phase. It can be concluded that the double-walled microspheres made of Glu-PLGA and PLGA polymers in a mass ratio of 1:1 can be a potential delivery system for pharmaceutical proteins.

Tunable delayed controlled release profile from layered polymeric microparticles

“…20,25,40,47 In this study, solvent evaporation parameters significantly influenced total protein loading for the MPs (p<0.01) with 2.7±0.4 μg and 3.9±0.4 μg BSA/mg particles for the short and long solvent evaporation groups, respectively. Spatial distribution of encapsulated protein was evaluated through confocal microscopy of MPs encapsulated with Alexa-568 conjugated-insulin.…”

“…17,20 Briefly, the DCM solution containing dissolved MPs was diluted 1:2 in 2.5% (w/v) sodium dodecyl sulphate and 0.1 N NaOH in DI water and thoroughly agitated for 1 hr at 37 °C. The mixture was then centrifuged to separate the aqueous/organic phases and the aqueous phase was removed and replenished.…”

“…11,14–16 Such composite layered structures may be fabricated via complex electrospraying techniques 17,18 or through a one-step production consisting of emulsion followed by solvent extraction/evaporation (ideal for hydrophobic cargo). 12,13 The one-step emulsion technique may also be adapted to encapsulate hydrophilic proteins (termed water-in-oil-in-oil-in-water; W/O 1 /O 2 /W) 19,20 to improve the bioactivity of encapsulated cargo during both particle fabrication and through the various phases of the release. 14,21 In this process, conventional emulsion techniques are used with two immiscible polymers (i.e.…”

“…Altering shell thickness/material of the layered MPs is the most common technique for tuning release profiles from layered PLGA/PLLA MPs. 17,18,20 Although newer techniques that use bi-/tricapillary electrosprayers impart greater control over particle population (diameter and polydispersity) and shell thickness compared to the W/O 1 /O 2 /W process, the requirement for specialized equipment impedes their widespread adoption. 17,18 Thus, in this work, we describe novel methods that build on the straightforward W/O 1 /O 2 /W emulsion to tune the distribution of hydrophilic protein within composite PLGA/PLLA MPs.…”

Preparation and Properties of Stereocomplex of Poly(lactic acid) and Its Amphiphilic Copolymers Containing Glucose Groups

“…Glucose, as the most common monosaccharide in nature, is well-known for its extensive sources, low price, nontoxicity, and high hydrophilicity, etc. Glucose possessing five hydroxyl groups is easily modified with PLA by blending [14,26] or copolymerization [27]. Because of its advantages, such as low cost, simple technology, and convenient operation, the direct polycondensation may be used to prepare PLA and its copolymers, and the obtained PLA usually has low molecular weights [28].…”