title: Ion pairing with linoleic acid simultaneously enhances encapsulation efficiency and antibacterial activity of vancomycin in solid lipid nanoparticles.
abstract: Ion pairing of a fatty acid with an antibiotic may be an effective strategy for formulation optimization of a nanoantibiotic system. The aim of this study was therefore to explore the potential of linoleic acid (LA) as an ion pairing agent to simultaneously enhance encapsulation efficiency and antibacterial activity of triethylamine neutralized vancomycin (VCM) in solid lipid nanoparticles (SLNs). The prepared VCM-LA2 conjugate was characterized by Fourier transform-infrared (FT-IR) spectroscopy, logP and binding energy calculations. The shifts in the FT-IR frequencies of COOH, NH2 and CO functionalities, an increase in logP value (1.37) and a lower interaction energy between LA and VCM (-125.54 kcal/mol) confirmed the formation of the conjugate. SLNs were prepared by a hot homogenization and ultrasonication method, and characterized for size, polydispersity index (PI), zeta potential (ZP), entrapment efficiency (%EE), surface morphology and physical stability. In vitro antibacterial activity studies against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) were conducted. Size, PI and ZP for VCM-LA2_SLNs were 102.7±1.01, 0.225±0.02 and -38.8±2.1 (mV) respectively. SLNs were also stable at 4 °C for 3 months. %EE for VCM-HCl_SLNs and VCM-LA2_SLNs were 16.81±3.64 and 70.73±5.96 respectively, indicating a significant improvement in encapsulation of the drug through ion pairing with LA. Transmission electron microscopy images showed spherical nanoparticles with sizes in the range of 95-100 nm. After 36 h, VCM-HCl showed no activity against MRSA. However, the minimum inhibitory concentration for VCM-HCl_SLNs and VCM-LA2_SLNs were 250 and 31.25 μg/ml respectively against S. aureus, while against MRSA it was 500 and 15.62 μg/ml respectively. This confirms the enhanced antibacterial activity of VCM-LA2_SLNs over VCM-HCl_SLNs. These findings therefore suggest that VCM-LA2_SLNs is a promising nanoantibiotic system for effective treatment against both sensitive and resistant S. aureus infections.
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Kalhapure
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Chunderika
authors.initials: C
authors.lastname: Mocktar
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Dhiraj R
authors.initials: DR
authors.lastname: Sikwal
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Sandeep J
authors.initials: SJ
authors.lastname: Sonawane
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Muthu K
authors.initials: MK
authors.lastname: Kathiravan
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Adam
authors.initials: A
authors.lastname: Skelton
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa. Electronic address: govenderth@ukzn.ac.za.
authors.forename: Thirumala
authors.initials: T
authors.lastname: Govender
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D007477:Ions; D019787:Linoleic Acid / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D013010:Sonication; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry; D013997:Time Factors; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D007477:Ions; D008055:Lipids; D013501:Surface-Active Agents; D014640:Vancomycin; D019787:Linoleic Acid
keywords: Encapsulation efficiency; Ion pairing; Linoleic acid; Methicillin-resistant Staphylococcus aureus (MRSA); Solid lipid nanoparticles; Vancomycin