Title:
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Development and characterisation of antibiotic-loaded semi-solid hydrogel formulations for the treatment of chronic ulceration
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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 PV A-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 PV A-borate hydro gels 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.
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