title: Polyelectrolyte complex of vancomycin as a nanoantibiotic: Preparation, in vitro and in silico studies.
abstract: Delivery of antibiotics by various nanosized carriers is proving to be a promising strategy to combat limitations associated with conventional dosage forms and the ever-increasing drug resistance problem. This method entails improving the pharmacokinetic parameters for accumulation at the target infection site and reducing their adverse effects. It has been proposed that antibiotic nanoparticles themselves are more effective delivery system than encapsulating the antibiotic in a nanosystem. In this study, we report on nanoparticles of vancomycin (VCM) by self-assembled amphiphilic-polyelectrolyte complexation between VCM hydrochloride and polyacrylic acid sodium (PAA). The size, polydispersity index and zeta potential of the developed nanoplexes were 229.7 ± 47.76 nm, 0.442 ± 0.075, -30.4 ± 5.3 mV respectively, whereas complexation efficiency, drug loading and percentage yield were 75.22 ± 1.02%, 58.40 ± 1.03% and 60.60 ± 2.62% respectively. An in vitro cytotoxicity study on three mammalian cell lines using MTT assays confirmed the biosafety of the newly formulated nanoplexes. Morphological investigations using scanning electron microscope showed cube shaped hexagonal-like particles. In vitro drug release studies revealed that the drug was completely released from the nanoplexes within 12h. In silico studies revealed that the nano-aggregation was facilitated by means of self-association of VCM in the presence of the polymer. The supramolecular pattern of the drug self-association was found to be similar to that of the VCM dimer observed in the crystal structure of the VCM available in Protein Data Bank. In vitro antibacterial activity against susceptible and resistant Staphylococcus aureus proved that the potency of VCM was retained after being formulated as the nanoplex. In conclusion, VCM nanoplexes could be a promising nanodrug delivery system to treat infections of S. aureus origin.
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X5400, Durban, South Africa.
authors.forename: Dhiraj R
authors.initials: DR
authors.lastname: Sikwal
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: Sanjeev
authors.initials: S
authors.lastname: Rambharose
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: 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.
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. 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 / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D000071228:Polyelectrolytes / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects; D013816:Thermodynamics; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D000071228:Polyelectrolytes; D014640:Vancomycin
keywords: Methicillin-resistant S. aureus; Nanoantibiotics; Nanoplex; Polyacrylic acid; S. aureus; Vancomycin