Development and characterisation of antibiotic-loaded semi-sold hydrogel formulations for the treatment of chronic ulceration

Abstract

The topical application of antimicrobial agents is becoming a key target area for the treatment of chronic infected wounds. This thesis evaluates the potential of novel semi-solid PVA-borate hydrogels to perform as a delivery vehicle for a range of therapeutic antimicrobial agents. The viscoelastic properties of PVA-borate gels allow formulations to flow into and make intimate contact with all surfaces of the wound, maximising drug exposure. The high water content of PVA-borate hydrogels also provides a moist environment, which promotes normal wound healing processes.

The topical antibiotics, mupirocin calcium (1.5% w/w), sodium fusidate (1.5% w/w) and gentamicin sulphate (1.0% w/w), were formulated into PVA-borate hydrogels to produce clear homogenous formulations. D-mannitol was utilised as a modulating excipient in the formulation of mupirocin calcium and gentamicin sulphate gels.

Silver nanoparticles offer an effective broad spectrum of activity at a lower cost to alternative antimicrobials. This thesis outlines the synthesis of silver nanoparticles in the range of 7-10 nm and their encapsulation within the cross-linked PVA-borate network.

The biguanide agents, polyhexamethylene biguanide hydrochloride and chlorhexidine digluconate, have been incorporated into PVA-borate hydrogels at a concentration of 0.1% w/w. In vitro drug release studies showed that PVA-borate hydrogels could be used as an effective delivery vehicle for biguanide agents.

This thesis demonstrates that all the antimicrobial-loaded PVA-borate hydrogel formulations developed exhibit prominent bacterial inhibitory effects against a range of gram-positive and gram-negative bacteria in vitro. Novel experimental techniques were developed to demonstrate antimicrobial loaded PVA-borate hydrogels activity against microorganisms in both the planktonic and biofilm phenotype. Microbiological analysis has illustrated their potential for the treatment of infected ulcerated lesions.

Thesis is embargoed until 30th June 2015

Date of Award	Jun 2013
Original language	English
Sponsors	Department for Employment and Learning (DEL)
Supervisor	Paul McCarron (Supervisor), John Callan (Supervisor) & Ahmed Faheem (Supervisor)