title: Co-encapsulation of multi-lipids and polymers enhances the performance of vancomycin in lipid-polymer hybrid nanoparticles: In vitro and in silico studies.
abstract: Nano-drug delivery systems are being widely explored to overcome the challenges with existing antibiotics to treat bacterial infections [1]. Lipid-polymer hybrid nanoparticles (LPNs) display unique advantages of both liposomes and polymeric nanoparticles while excluding some of their limitations, particularly the structural integrity of the polymeric particles and the biomimetic properties of the liposome [1]. The use of helper lipids and polymers in LPNs has not been investigated, but has shown potential in other nano-drug delivery systems to improve drug encapsulation, antibacterial activity and drug release. Therefore, LPNs using co-excipients were prepared using vancomycin (VCM), glyceryl triplamitate and Eudragit RS100 as the drug, lipid and polymer respectively. Oleic acid (OA), Chitosan (CHT) and Sodium alginate (ALG) were explored as co-excipients. Results indicated rod-shaped LPNs with suitable size, PDI and zeta potential, while encapsulation efficiency (%EE) increased from 27.8% to 41.5%, 54.3% and 69.3% with the addition of OA, CHT and ALG respectively. Drug release indicated that VCM-CHT had the best performance in sustained drug release of 36.1 ± 5.35% after 24h. The EE and drug release were further corroborated by in silico and release kinetics data. In vitro antibacterial studies of all formulations exhibited better activity against bare VCM and sustained activity up to day 5 against both Staphylococcus aureus and MRSA, with VCM-OA and VCM-CHT showing better activity against MRSA. Therefore, this LPN proves to be a promising system for delivery of VCM as well as other antibiotics.
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa.
authors.forename: Nasreen
authors.initials: N
authors.lastname: Seedat
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Kalhapure
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa.
authors.forename: Chunderika
authors.initials: C
authors.lastname: Mocktar
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa.
authors.forename: Suresh
authors.initials: S
authors.lastname: Vepuri
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa.
authors.forename: Mahantesh
authors.initials: M
authors.lastname: Jadhav
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa. Electronic address: govenderth@ukzn.ac.za.
authors.forename: Thirumala
authors.initials: T
authors.lastname: Govender
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000464:Alginates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007700:Kinetics; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014280:Triglycerides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014640:Vancomycin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000180:Acrylic Resins; D000464:Alginates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D014280:Triglycerides; D019301:Oleic Acid; C050528:Eudragit RS; D014640:Vancomycin; D020723:Glucuronic Acid; D048271:Chitosan; C005859:tripalmitin
keywords: Antibacterial; In silico; Lipid–polymer; MRSA; Nanoparticle; Vancomycin