Abstract
Drug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (−18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.
Highlights
Www.nature.com/scientificreports hypoglycemic drugs commonly prescribed in type 2 diabetes mellitus (T2DM) management are sulphonylureas, meglitinides, and thiazolidinediones therapeutic categories, belong to Biopharmaceutical Classification System (BCS) type II compounds with low solubility and high permeability
The prime objective of this study was to design, develop and explore the potential application of second-generation polymeric nanocrystal technology to overcome the formulation and drug delivery challenges associated with gliclazide, a first-line oral hypoglycemic, BCS class II drug used in T2DM management
The optimized gliclazide loaded PLGA second-generation formulation SGNCF1 was developed by employing Taguchi experimental design and characterized for particle size, zeta potential, solubility studies, drug entrapment, surface morphology studies, in vitro drug release studies, drug excipient compatibility study, in vivo performance study and stability studies
Summary
Www.nature.com/scientificreports hypoglycemic drugs commonly prescribed in T2DM management are sulphonylureas, meglitinides, and thiazolidinediones therapeutic categories, belong to Biopharmaceutical Classification System (BCS) type II compounds with low solubility and high permeability. The bottom-up and top-down techniques, as well as the combinations of both can produce SGNCs. Second generation smarter nanocrystals of oral hypoglycemic, BCS class II drugs are achieved by using biodegradable polymers, stabilizer and drug, employing specialized pre-combinative treatment strategies such as Emulsion diffusion high-pressure homogenization - Solvent evaporation (EHS) techniques[40,41,42]. This research study postulated that gliclazide, oral hypoglycemic BCS class II drug loaded PLGA Second generation smarter nanocrystals may overcome the drug delivery challenges such as poor solubility, low and variable bioavailability, irreproducible therapeutic response, a large amount of oral dose for conventional dosage. The present study is aimed to design, develop and delivery of gliclazide SGNCs, produced by pre-combinative strategies such as emulsion diffusion, high-pressure homogenization and solvent evaporation method using PLGA biodegradable polymers in combination with a stabilizer such as Poloxamer 188, PEG 4000, HPMC-E15. The formulated gliclazide SGNCs were investigated on physicochemical properties, in vitro drug release and in vivo performance such as pharmacokinetic-pharmacodynamic correlation, therapeutic efficacy and bioavailability studies using streptozotocin/nicotinamide-induced type-2 diabetes rat model[43,44]
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