title: Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System.
abstract: A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-β) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-β and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-β peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
authors.forename: Pierre P D
authors.initials: PPD
authors.lastname: Kondiah
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
authors.forename: Lomas K
authors.initials: LK
authors.lastname: Tomar
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
authors.forename: Charu
authors.initials: C
authors.lastname: Tyagi
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa.
authors.forename: Thashree
authors.initials: T
authors.lastname: Marimuthu
authors.affiliation: Department of Neurosciences, Division: Neurology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,, 7 York Road, Parktown 2193, South Africa. viness.pillay@wits.ac.za.
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004921:Erythropoietin / Q000008:administration & dosage*; D065570:Gastric Absorption; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage*; D016899:Interferon-beta / Q000008:administration & dosage* / Q000097:blood; D008689:Methacrylates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008689:Methacrylates; C421283:poly(ethylene glycol)-dimethacrylate; D004921:Erythropoietin; D011092:Polyethylene Glycols; D016899:Interferon-beta
keywords: copolymeric microparticulate system; erythropoietin (EPO); gastric and intestinal absorptive system; insulin; interferon-β (INF-β); oral route; protein-loaded