Abstract
Diabetic populations are more prone to developing wound infections which results in poor and delayed wound healing. Infection with drug resistant organisms further worsen the situation, driving searches for alternative treatment approaches such as phage therapy. Major drawback of phage therapy, however, is low phage persistence in situ, suggesting further refinement of the approach. In the present work we address this issue by employing liposomes as delivery vehicles. A liposome entrapped phage cocktail was evaluated for its ability to resolve a Staphylococcus aureus-induced diabetic excission wound infection. Two characterized S. aureus specific lytic phages, MR-5 and MR-10 alone, in combination (cocktail), or entrapped in liposomes (versus as free phages) were assesed for their therapeutic efficacy in resolving diabetic wound infection. Mice treated with free phage cocktail showed significant reduction in wound bioburden, greater wound contraction and faster tissue healing than with free monophage therapy. However, to further enhance the availability of viable phages the encapsulation of phage cocktail in the liposomes was done. Results of in vitro stability studies and in vivo phage titer determination, suggests that liposomal entrapment of phage cocktail can lead to better phage persistence at the wound site. A 2 log increase in phage titre, however, was observed at the wound site with liposome entrapped as compared to the free phage cocktail, and this was associaed with increased rates of infection resolution and wound healing. Entrapment of phage cocktails within liposomes thus could represent an attractive approach for treatment of bacterial infections, not responding to antibiotis as increased phage persistence in vitro and in vivo at the wound site was observed.
Highlights
Diabetes is a chronic disease that manifests in the form of a chronic hyperglycemia which is associated with a plethora of complications including visual impairment, blindness, kidney disease, nerve damage, amputation, heart disease, and stroke (Loghmani, 2005)
Toward improving phage persistence and retention at diabetic wound sites, we propose here the use of liposome entrapment of phages
S. aureus specific phages, MR-5 and MR-10, both of which have been isolated and characterized in our laboratory as lytic, dsDNA, tailed phages belonging to Myoviridae family, order Caudovirales were used in the present study (Kaur et al, 2012; Chhibber et al, 2013)
Summary
Diabetes is a chronic disease that manifests in the form of a chronic hyperglycemia which is associated with a plethora of complications including visual impairment, blindness, kidney disease, nerve damage, amputation, heart disease, and stroke (Loghmani, 2005). The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030 (Wild et al, 2004). Diabetic patients are five times more susceptible to fungal and bacterial infections (Axelrod, 1985). This is due to several factors that include a high glucose level which. Treatment of MRSA in Diabetic Mice encourages bacterial growth. Staphylococcus aureus is one of the most common pathogens isolated from wounds in diabetic patients. With the spread of methicillin resistant strains of S. aureus (MRSA), management of such infections in diabetic population has become challenging. Diabetics who contract MRSA are at a greater risk of harboring more serious, slow-healing wounds (Rogers and Bevilacqua, 2009)
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