ABSTRACT
PURPOSE: In the present study, biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) containing insulin were loaded in sodium alginate/jeffamine (ALG/jeff) hydrogel for prolonged delivery of insulin. The main aim of this work was to fabricate an efficient insulin delivery system to improve patient adherence by decreasing the repetition of injections. METHODS: Swelling and morphological properties and crosslinking efficiency of ALG/jeff hydrogel were assessed. The composite hydrogel was prepared by adding PHBV NPs to ALG/jeff hydrogel concurrently with crosslinking process. The morphology and loading capacity of composite hydrogel were analyzed. RESULTS: Circular dichroism measurement demonstrated that insulin remains stable following fabrication process. The release profile exhibited 54.6â¯% insulin release from composite hydrogel within 31 days with minor initial burst release equated to nanoparticles and hydrogels. MTT cell viability analysis was performed by applying L-929 cell line and no cytotoxic effect was observed. CONCLUSIONS: Favorable results clearly introduced fabricated composite hydrogel as an excellent candidate for drug delivery systems and also paves the route for prolonged delivery systems of other proteins.
Subject(s)
Alginates , Cell Survival , Delayed-Action Preparations , Hydrogels , Insulin , Nanoparticles , Polyesters , Alginates/chemistry , Insulin/administration & dosage , Insulin/chemistry , Hydrogels/chemistry , Nanoparticles/chemistry , Cell Survival/drug effects , Polyesters/chemistry , Animals , Delayed-Action Preparations/chemistry , Mice , Cell Line , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Drug Delivery Systems/methods , Drug Carriers/chemistry , Drug Liberation , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , PolyhydroxybutyratesABSTRACT
The purpose of this research was the fabrication, statistical optimization, and in vitro characterization of insulin-loaded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles (INS-PHBV-NPs). Nanopar-ticles were successfully developed by double emulsification solvent evaporation method. The NPs were characterized for particle size, entrapment efficiency (EE%), and polydispersity index (PDI). The NPs also were characterized by scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and circular dichroism (CD). The optimum conditions were found to be 1.6% polyvinyl alcohol (PVA), 0.9% of PHBV, and 15 mg/ml of insulin with the aid of the Box-Behnken experimental design results. The optimized NPs showed spherical shape with particle size of 250.21 ± 11.37 nm, PDI of 0.12 ± 0.01, and with EE% of 90.12 ± 2.10%. In vitro drug release pattern followed Korsmeyer-Peppas model and exhibited an initial burst release of 19% with extended drug release of 63.2% from optimized NPs within 27 d. In conclusion, these results suggest that INS-PHBV-NPs could be a promising candidate for designing an injectable sustained release formulation for insulin.