title: Design of an Inflammation-Sensitive Polyelectrolyte-Based Topical Drug Delivery System for Arthritis.
abstract: The most successful treatment strategy for arthritis is intra-articular injections that are costly and have reduced patient compliance. The purpose of the current study was to develop an inflammation-sensitive system for topical drug administration. Multi-macromolecular alginate-hyaluronic acid-chitosan (A-H-C) polyelectrolyte complex nanoparticles, loaded with indomethacin were developed employing pre-gel and post-gel techniques in the presence of dodecyl-L-pyroglutamate (DLP). In addition to in vitro studies, in silico simulations were performed to affirm and associate the molecular interactions inherent to the formulation of core all-natural multi-component biopolymeric architectures composed of an anionic (alginate), a cationic (chitosan), and an amphi-ionic polyelectrolytic (hyaluronic acid) macromolecule. The results demonstrated that DLP significantly influenced the size of the synthesized nanoparticles. Drug-content analysis revealed higher encapsulation efficiency (77.3%) in the presence of DLP, irrespective of the techniques used. Moreover, in vitro drug release studies showed that indomethacin release from the nanosystem was significantly improved (98%) in Fenton's reagent. Drug permeation across a cellulose membrane using a Franz diffusion cell system showed an initial surge flux (0.125 mg/cm(-2)/h), followed by sustained release of indomethacin for the post-gel nanoparticles revealing its effective skin permeation efficiency. In conclusion, the study presents novel nanoparticles which could effectively encapsulate and deliver hydrophobic drugs to the target site, particularly for arthritis.
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: Divya
authors.initials: D
authors.lastname: Bijukumar
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: Karmani
authors.initials: K
authors.lastname: Murugan
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: Bibi Fatima
authors.initials: BF
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: 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. viness.pillay@wits.ac.za.
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000287:Administration, Topical; D000464:Alginates / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry*; D001168:Arthritis / Q000188:drug therapy*; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy*; D008566:Membranes / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D000071228:Polyelectrolytes / Q000737:chemistry*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000464:Alginates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005782:Gels; D006603:Hexuronic Acids; D000071228:Polyelectrolytes; C057997:dodecyl pyroglutamate; D020723:Glucuronic Acid; D002482:Cellulose; D006820:Hyaluronic Acid; D048271:Chitosan; D011761:Pyrrolidonecarboxylic Acid; D007213:Indomethacin
keywords: alginate; chitosan; dodecyl-L-pyroglutamate; drug delivery; hyaluronan; inflammation; topical