Multifactorial design of poly(d,l‐lactic‐co‐glycolic acid) capsules with various release properties for differently sized filling agents

Abstract

The hydrolytic degradation and corresponding content release of capsules made of poly(D,L-lactic-co-glycolic acid) (PLGA) strongly depends on the composition and material properties of the initially applied copolymer. Consecutive or simultaneous release from capsule batches of combinable material compositions, therefore, offers high control over the bioavailability of an encapsulated drug. The keynote of this study was the creation of a superordinated database that addressed the correlation between the release kinetics of filling agents with different molecular weights from PLGA capsules of alternating composition. Fluorescein isothiocyanate (FITC)-dextran (with molecular weights of 4, 40, and 2000 kDa) was chosen as a model analyte, whereas the copolymers were taken from various 50:50 PLGA, 75:25 PLGA, and polylactide blends. With reference to recent publications, the capsule properties, such as the size, morphology, and encapsulation efficiency, were further modified during production. Hence, uniform microdisperse and polydisperse submicrometer nanocapsules were prepared by two different water-in-oil-in-water emulsification techniques, and additional effects on the size and morphology were achieved by capsule solidification in two different sodium salt buffers. The qualitative and quantitative examination of the physical capsule properties was performed by confocal laser scanning microscopy, scanning electron microscopy, and Coulter counting techniques to evaluate the capsule size distribution and the morphological appearance of the different batches. The corresponding agent release was quantified by fluorescence measurement of the FITC-dextran in the incubation media and by the direct measurement of the capsule brightness via fluorescence microscopy. In summary, the observed agent release showed a highly controllable flexibility depending on the PLGA blends, preparation methods, and molecular weight of the used filling substances.

New promising biodegradable polyesters derived from poly((R,S)-3,3-dimethylmalic acid) for cardiovascular applications

“…The co-monomers relative contents (10,20, and 30 %) were obtained by 1 H NMR using the integration ratio of peak at 4.15 ppm corresponding to -CH 2 -O-hexyl and that at 5.20 ppm corresponding to -CH 2 -O-benzyl (Figure 12). After a catalytic hydrogenolysis in presence of 10 % of palladium on charcoal on the polyester, it is possible to obtain carboxylic acid group (when R = −CH 2 Ph) and alcohol group (when R = −(CH 2 ) 3 -O-CH 2 Ph) (Scheme 5).…”

“…These biodegradable polyesters were used either alone or as copolymers side chains to improve their mechanical properties, hydrolysis, long-term biodegradation, or biocompatibility behavior for the desired therapeutic applications (PLGA [9,10], PLMA [11][12][13][14][15], etc.). Among this class of polymers, the PMLA is known to present good biocompatibility, non-toxicity in vitro and in vivo, non--immunogenic properties, and stability in the bloodstream [5,[16][17][18][19].…”