Influence of Poloxamer 188 on Design and Development of Second Generation PLGA Nanocrystals of Metformin Hydrochloride

Abstract

The poly(D,L-lactide-co-glycolide) (PLGA) based second-generation nanocrystals prepared by modified nanoprecipitation method, is the method of choice for encapsulation of both lipophilic and hydrophilic drugs. In this study, nanoprecipitation technique was adopted to develop second generation nanocrystals of PLGA loaded with metformin HCl (MHc). Poloxamer 188 with three different concentrations (0.5, 0.75, 1% w/v) in combination with PLGA at 1, 2, 3% concentrations (w/v) successfully produced MHc loaded PLGA second generation nanocrystals. The effects of poloxamer 188, amphiphilic triblock copolymer on carrier particle size, surface morphology, polydispersity index, zeta potential, drug entrapment efficiency and drug release of nanoformulation were investigated. The optimized formulation of second-generation nanocrystals with concentrations 0.75% w/v poloxamer 188 and 2% w/v PLGA, could produce particle size of 114.6 nm, entrapment efficiency of 63.48% and drug release 80.23% at 12 h. A blank formulation with the same composition as optimized formulation without addition of poloxamer188 compared with optimized formulation, exhibited nanoparticles of larger mean particle size of 212.9 nm with entrapment efficiency of 68.47% and 50.5% drug release at 12 h. Transmission electron microscopy (TEM) analysis of the nanoformulations revealed that poloxamer188 greatly contributed to smooth, spherical morphology of nanosize polymeric nanoparticles. Further Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies on nanoformulation emphasized the significance of poloxamer188 in formulation and development of optimized MHc loaded PLGA nanosuspensions of second generation nanocrystals. In conclusion, the study emphasizes that poloxamer 188 was a versatile excipient, which played a pivotal role in producing nanosize carrier with high drug release profile of MHc loaded PLGA nanosuspensions of second generation nanocrystals.

Investigating the Impact of Optimized Trans-Cinnamic Acid-Loaded PLGA Nanoparticles on Epithelial to Mesenchymal Transition in Breast Cancer

“…Extra fluid was then eliminated by with the aid of an absorbent paper, then observed by TEM (JEM 1010, JEOL Ltd, Tokyo, Japan) with an acceleration voltage of 70kV and magnification power of 150 KX. 29 , 30 …”

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

“…The morphological and physicochemical characterizations of the gliclazide-loaded PVA/PLGA nanofibers were performed. The fabricated gliclazide nanofibers were extensively investigated for solubility studies, in vitro drug release studies, drug release kinetic studies, scanning electron microscopy studies (SEM), differential scanning calorimetric (DSC) studies and Fourier transform infrared (FTIR) spectroscopy studies and discussed in detail [10][11][12][13].…”

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

“…Type 2 diabetes mellitus (T2DM), is a non-communicable metabolic disorder characterized by high blood glucose, insulin resistance and relative insulin deficiency in the body. T2DM causes significant mortality and morbidity globally, which draws considerable attention from the public, policymakers and public health care providers for its mitigation and treatment 1,2 . According to the International Diabetes Federation (IDF), the global statistical data projected that 592 million people may have diabetes by the year 2035 and proportionally T2DM will increase in every country of the globe 3 .…”

“…At present, the available hypoglycemic therapeutic agents are not successful in chronic treatment and management of T2DM due to failure in drug delivery, severe adverse effects and patient noncompliance associated with therapy management. There is a high demand for a holistic strategy, which focuses on prevention and intervention of a novel therapeutic approach in drug delivery to fight the menace of an inexorable T2DM 1,6 . Oral 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 formulation strategies used in design, development, and delivery of polymeric SGNCs are simple, convenient, reliable and reproducible, which display remarkable improvement in solubility and bioavailability with a low therapeutic dose of BCS Class II drug. Novel possibilities of SGNCs application was explored and expedited by using poly (D, L-lactide-co-glycolide) PLGA based polymeric nanocrystal composite system as a modified delayed drug delivery carrier for BCS class II, oral hypoglycemic drug 1,29,30 . PLGA is a biodegradable and biocompatible polymer, most commonly and successfully used as a polymeric nanoparticulate drug delivery system for many therapeutic agents 31,32 .…”