Fabrication of Second Generation Smarter PLGA Based Nanocrystal Carriers for Improvement of Drug Delivery and Therapeutic Efficacy of Gliclazide in Type-2 Diabetes Rat Model

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.

Design, Fabrication and Characterization of PVA/PLGA Electrospun Nanofibers Carriers for Improvement of Drug Delivery of Gliclazide in Type-2 Diabetes

“…Then, the resultant solution was further added to the PBS solution and analyzed for drug contents using the UV spectrophotometer by Perki-nElmer Lambda XLS, at 228 nm, against the blank solutions. Each experiment was carried out in triplicate [3].…”

“…Gliclazide belongs to Biopharmaceutical Classification Systems (BCS) class II drugs, with low solubility and high membrane permeability and lipophilicity. The low solubility and dissolution rate of Gliclazide result in variable gastrointestinal absorption following oral administration cause erratic bioavailability [3]. Hence, to improve the drug delivery challenges and therapeutic efficacy of gliclazide in type 2 diabetes mellitus (T2DM), a polymeric nanofiber specialized carrier system for oral delivery of gliclazide was explored in this study.…”

“…There is a huge demand to design and develop a suitable delivery system which meets the typical physiological needs of T2DM. The specialized oral delivery system, which modifies the drug release as per plasma glucose requirement and improves patient compliance, is of great importance in T2DM [3,4]. A few studies reported that incorporation of gliclazide into polymer matrices such as solid dispersion and nanocrystal formulation improved solubility, dissolution rate and achieve sustained release of the drug.…”

“…PLGA was also selected as a secondary polymer to modulate the drug release of gliclazide loaded PVA nanofibers. PLGA has been commonly applied as a biocompatible polymer in achieving sustained drug delivery over a prolonged period of time of many therapeutics reported [3,6,7]. In this study, different concentrations of PLGA at 0.05%, 0.10% and 0.15% w/v were added to PVA to achieve a modified drug release profile to meet the typical physiological needs of T2DM, such as a faster drug release at the time of meals followed by prolonged drug release profile over an extended period to maintain constant plasma glucose level, highly desirable for better T2DM management [8].…”

Stable solid dispersion of lurasidone hydrochloride with augmented physicochemical properties for the treatment of schizophrenia and bipolar disorder

“…Drugs that are showing poor aqueous solubility are classified in BCS class II and IV category (Amidon, Lennernäs, Shah, & Crison, 1995). The aqueous solubility issue eventually leads to erratic absorption through gastrointestinal (GI) tract when administered orally which in turn ends to compromised availability of drug in the systemic circulation (Panda, Krishnamoorthy, Bhattamisra, & Shivashekaregowda, 2019). The poor bioavailability resulting from poor aqueous solubility and dissolution rate of active pharmaceutical ingredient, is a major issue that has been faced by the formulation scientist during successful product development and resulted in discarding of a vast number of discovery pipeline molecules (Merisko‐Liversidge et al, 1996).…”