Pyramid-Shaped PEG-PCL-PEG Polymeric-Based Model Systems for Site-Specific Drug Delivery of Vancomycin with Enhance Antibacterial Efficacy

Sima Singh; Majed M Alrobaian; Nagashekhara Molugulu; Nikhil Agrawal; Arshid Numan; Prashant Kesharwani

doi:10.1021/acsomega.9b04064

Pyramid-Shaped PEG-PCL-PEG Polymeric-Based Model Systems for Site-Specific Drug Delivery of Vancomycin with Enhance Antibacterial Efficacy

ACS Omega. 2020 May 18;5(21):11935-11945. doi: 10.1021/acsomega.9b04064. eCollection 2020 Jun 2.

Authors

Sima Singh¹, Majed M Alrobaian², Nagashekhara Molugulu³, Nikhil Agrawal¹, Arshid Numan⁴, Prashant Kesharwani⁵

Affiliations

¹ Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
² Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif 21974, Kingdom of Saudi Arabia.
³ School of Pharmacy, Monash University, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia.
⁴ State Key Laboratory of ASIC and System, SIST, Fudan University, 200433 Shanghai, China.
⁵ Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, 110062 New Delhi, India.

Abstract

Antibacterial resistance remains a major global problem due to frequent prescriptions, leading to significant toxicities. To overcome the limitations of antibiotic therapy, it is highly desirable to provide site-specific delivery of drugs with controlled release. Inspired by the biocompatible, biodegradable, and site-specific mimicking behavior of poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL), we developed vancomycin-PEG-PCL-PEG conjugates to maximize the pharmacological effects and minimize the side effects. Drug-loaded vancomycin-PEG-PCL-PEG conjugates are influenced by size, shape, surface area, encapsulation efficiency, in vitro drug release, hemolysis assay, cytotoxicity, and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and bacterial kill kinetics. The results demonstrated that vancomycin (VCM) release from PEG-PCL-PEG triblock revealed a biphasic manner. Hemolysis assay showed the nonprescription nature of VCM-PEG-PCL-PEG. Cytotoxicity studies confirmed the biocompatibility of VCM-PEG-PCL-PEG. The in vitro antibacterial results showed enhance activity with minimum inhibitory concentration compared to bare VCM. Molecular dynamics simulation study revealed that binding between VCM and PEG-PCL-PEG by hydrophobic interactions offers molecular encapsulation and steric barrier to drug degradation. This newly developed therapeutic delivery system can offer to enhance activity and delivery VCM against MRSA.