title: Ultra-small lipid-dendrimer hybrid nanoparticles as a promising strategy for antibiotic delivery: In vitro and in silico studies.
abstract: The purpose of this study was to explore the preparation of a new lipid-dendrimer hybrid nanoparticle (LDHN) system to effectively deliver vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) infections. Spherical LDHNs with particle size, polydispersity index and zeta potential of 52.21±0.22 nm, 0.105±0.01, and -14.2±1.49 mV respectively were prepared by hot stirring and ultrasonication using Compritol 888 ATO, G4 PAMAM- succinamic acid dendrimer, and Kolliphor RH-40. Vancomycin encapsulation efficiency (%) in LDHNs was almost 4.5-fold greater than in lipid-polymer hybrid nanoparticles formulated using Eudragit RS 100. Differential scanning calorimetry and Fourier transform-infrared studies confirmed the formation of LDHNs. The interactions between the drug-dendrimer complex and lipid molecules using in silico modeling revealed the molecular mechanism behind the enhanced encapsulation and stability. Vancomycin was released from LDHNs over the period of 72 h with zero order kinetics and super case II transport mechanism. The minimum inhibitory concentration (MIC) against S. aureus and MRSA were 15.62 μg/ml and 7.81 μg/ml respectively. Formulation showed sustained activity with MIC of 62.5 μg/ml against S. aureus and 500 μg/ml against MRSA at the end of 72 and 54 h period respectively. The results suggest that the LDHN system can be an effective strategy to combat resistant infections.
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. Electronic address: kalhapure@ukzn.ac.za.
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: Sanjeev
authors.initials: S
authors.lastname: Rambharose
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: Suresh B
authors.initials: SB
authors.lastname: Vepuri
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001 Durban, 4000, South Africa.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
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 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D050091:Dendrimers / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D005227:Fatty Acids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009757:Nylons / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D050091:Dendrimers; D004337:Drug Carriers; D005227:Fatty Acids; D009757:Nylons; C520550:PAMAM-G4; C086409:glyceryl behenate; D014640:Vancomycin
keywords: Antibiotic; Bacterial resistance; Dendrimer; Hybrid nanoparticles; Lipid; MRSA; Sustained release