In Vitro Release of Lysozyme from Gelatin Microspheres: Effect of Cross-linking Agents and Thermoreversible Gel as Suspending Medium

Abstract

This study was aimed to characterize the microstructure and the performance of gelatin microspheres (GMs) cross-linked by two different cross-linkers viz. d-glucose and glutaraldehyde. New formulations were obtained, suspending the GMs in a thermoreversible Pluronic F127 (PF127) liquid-crystalline gel. Lysozyme was used as a model biomacromolecular drug to evaluate release features. Both types of cross-linked GMs were prepared by thermal gelation method. The lysozyme-loaded microspheres were characterized by scanning electron microscopy (SEM) for size distribution, shape, and surface texture. SEM revealed that both types of lysozyme-loaded GMs were spherical in shape and that the surface of glutaraldehyde cross-linked GMs was smoother than that of the glucose cross-linked GMs. The degree of cross-linking of microspheres was investigated using ATR-FTIR technique. The prepared GMs were suspended in 20% w/v aqueous PF127 gel for which the usual sol-gel transition temperature of 22 °C did not change in the presence of GMs, as indicated by rheological measurements. SAXS study of the PF127 gel confirmed the occurrence of a discrete cubic liquid-crystalline phase of the Fm3m type whose lattice parameter slightly decreased as a result of GMs addition. The in vitro release of lysozyme from both types of cross-linked GMs was successfully controlled when they were suspended in PF127 gel, thus suggesting the potential use of this new combined formulation as a drug-depot system.

Recent Developments in Protein and Peptide Parenteral Delivery Approaches

“…In another study, Hiwale and co-workers studied combined formulation of gelatin microspheres and thermoreversible gel as a drug-depot system for lysozyme [161]. Gelatin microspheres (GMs) loaded with lysozyme were prepared using two different cross linking agents: d -glucose and glutaraldehyde.…”

Functionalization of Cationic Polymers for Drug Delivery Applications

“…[1][2][3][4] Being categorized as a safe excipient by the US Food and Drug Administration (FDA), gelatine has shown great promise as a component of biomaterials in many medical applications. 5,6 For example, gelatine nanoparticles have been successfully utilized for non-viral plasmid DNA delivery 7 and cationic gelatine plasmid DNA polyplexes, i.e.…”

Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot

“…Many approaches have been adopted to modulate drug release kinetics, among which a combination of different delivery systems is a simple one. For example, to decrease burst release, microspheres in combination with in situ gels have been reported in some studies; [19][20][21] however, few, if any, studies have reported on PEGylation in combination with ISFS. PEG is the most successful candidate …”