title: Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation.
abstract: Mangiferin (Mgf), largely expressed out from the leaves and stem bark of Mango, is a potent antioxidant. However, its in vivo activity gets tremendously reduced owing to poor aqueous solubility and inconsistent gastrointestinal absorption, high hepatic first-pass metabolism and high P-gp efflux. The current research work, therefore, was undertaken to overcome the biopharmaceutical hiccups by developing the Mgf-phospholipid complex (PLCs) loaded in nanostructured lipidic carriers (NLCs). The PLCs and NLCs were prepared using refluxing, solvent evaporation and hot emulsification technique, respectively with three molar ratios of Mgf and Phospholipon 90G, i.e., 1:1; 1:2; and 1:3. The complex was evaluated for various physicochemical parameters like drug content (96.57%), aqueous solubility (25-fold improved) and oil-water partition coefficient (10-fold enhanced). Diverse studies on the prepared complex using FTIR, DSC, PXRD and SEM studies ratified the formation of PLCs at 1:1 ratio. The PLCs were further incorporated onto NLCs, which were systematically optimized employing a face centered cubic design (FCCD), while evaluating for particle size, zeta potential, encapsulation efficiency and in vitro drug release as the CQAs. Caco-2 cell line studies indicated insignificant cytotoxicity, and P-gp efflux, while bi-directional permeability model and in situ perfusion studies specified enhanced intestinal permeation parameters. In vivo pharmacokinetic studies revealed notable increase in the values of Cmax(4.7-fold) and AUC (2.1-fold), respectively, from PLCs-loaded NLCs vis-à-vis Mgf solution. In a nutshell, the promising results observed from the present research work signify enhanced biopharmaceutical attributes of the novel PLCs-loaded NLCs for potentially augmenting the therapeutic efficacy of Mgf.
authors.affiliation: UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Rajneet Kaur
authors.initials: RK
authors.lastname: Khurana
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India.
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Bansal
authors.affiliation: UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.
authors.forename: Andrea Julie
authors.initials: AJ
authors.lastname: Burrow
authors.affiliation: UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: O P
authors.initials: OP
authors.lastname: Katare
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.
authors.forename: Kamalinder K
authors.initials: KK
authors.lastname: Singh
authors.affiliation: UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India; UGC- Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160014, India. Electronic address: bsbhoop@yahoo.com.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D006801:Humans; D007408:Intestinal Absorption; D062105:Molecular Docking Simulation; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012995:Solubility; D044004:Xanthones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D010743:Phospholipids; D044004:Xanthones; C013592:mangiferin
keywords: Antioxidants; Caco-2 bidirectional permeability assay; Molecular docking; P-gp efflux; Phytomolecule; QbD; SPIP