Antimicrobial wafers as a novel technology for infection control in chronic wounds.

Bacterial contamination and persistent infection is a common cause of impaired wound healing. Generally, non-healing wounds display similar physiological features with regards to mixed bacterial flora, ischemia and production of exudate. The application of topical, broad spectrum antimicrobial compounds embedded in absorbent dressings has been shown to control bioburden and improve healing. Lyophilised, biopolymeric antimicrobial wafers can offer a contemporary, user-friendly, self-adhesive and effective approach for the management of suppuration and polybacterial contamination in a wide range of non-healing wounds. Cohesive, non-friable, porous, disc shape wafers were successfully produced with sodium alginate (SA) (18.17 plusminus 0.70 Pa.s), guar gum (GG) (82.21 plusminus 5.41 Pa.s; 95.87 plusminus 2.31 Pa), xanthan gum (XG) (2.86 plusminus 0.12 Pa.s; 23.61 plusminus 0.68 Pa), karaya gum (KAG) (12.89 plusminus 0.93 Pa.s) and an original gel consisting of a blend of a synergistic SA-KAG (7.75 plusminus 0.64 Pa.s; 86.34 plusminus 5.19 Pa) (1:1 ratio). Clinical concentrations of the broad spectrum, topical, antimicrobial compounds, neomycin sulphate (0.5 % w/v NS), chlorhexidine digluconate (0.5 % v/v CHD), povidone iodine (1.0 % v/v PVP-I) and silver sulfadiazine (1.0 % w/v SS) were mixed with compatible biopolymers and appeared to alter the rheological properties of the biopolymers. Rheological analysis of pre-lyophilised gels was undertaken to quantify the flow properties of the gels. The necessity of producing sterile wafers was investigated by exposing all biopolymer-antimicrobial combinations to 25 and 40 kGy of gamma irradiation. Gamma-rays caused total degradation of GG, KAG, SA and SA-KAG, while XG appeared to withstand irradiation. A novel free standing dissolution raft (FSDR) was designed and used to quantify the CHD released from both gels and wafers. CHD released from wafers ranged from 3.5 plusminus 0.01 to 17.4 plusminus 0.39 %. Gels and wafers released CHD in a sustained manner and the release profile of wafers was similar to the respective gels, with the exception of GG. Neither gels nor wafers released 100% of the incorporated antimicrobial indicating that drug-polymer interactions governed the general performance of antimicrobial wafers, in terms of adhesion, expansion ratio (ER), inhibition ratio (IR), water uptake capacity (WUC) and antimicrobial delivery. Molecular modelling studies undertaken for KAG-antimicrobial complexes demonstrated an unusual Z-shape geometry for cationic CHD. The charge and geometry of CHD was plausibly responsible for the antimicrobials entrapment within biopolymeric networks. The efficacy of antimicrobial wafers was demonstrated in vitro under simulated conditions of an exuding wound using modified disc diffusion and an original antimicrobial diffusion cell (ADC). All wafers were effective in vitro against common chronic wound pathogens of such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), E. coli and P. aeruginosa. Antimicrobial activity depended on the sensitivity of the microorganisms to a specific antimicrobial compound and the presence of organic material. Data obtained demonstrated that the presence of protein (BSA) in the pseudo-exudate inhibited the antimicrobial activity of CHD and PVP-I, while enhancing the antimicrobial activity of SS and NS against MRSA. The general findings summarised in this thesis conclude that factors such as protein content, electrolyte content and pH of exudate play a key role in the efficacy of self-adhesive, absorbent formulations intended for the topical delivery of antimicrobial compounds to non-healing, infected wounds. Drug-polymer interactions developed between biopolymers and incorporated antimicrobial compounds have a profound effect on the general performance of lyophilised antimicrobial wafers