Bioactivity of gentamicin contained in novel transdermal drug delivery systems (TDDS) formulated with biodegradable polyesters

Abstract

Topical administration of gentamicin, a hydrophilic aminoglycoside antibiotic, is limited by membrane impermeability and toxicity concerns. The purpose of this study was to develop and evaluate the antimicrobial activities of an alternative non-invasive, convenient and cost-effective transdermal drug delivery system (TDDS) containing gentamicin in biodegradable polyester-based matrices. The patches were formulated by solvent evaporation technique using PURASORB ® polymers and evaluated for thermal properties, drug content, physicochemical performance, stability, skin irritation on rat skin and antimicrobial activities against five micro-organisms: Staphylococcus aureus, Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The differential scanning calorimetry (DSC) results indicated compatibilty between the drug and the polymers. In addition, the formulations showed good drug encapsulation, stability, physicochemical properties, tolerability on rabbit skin and higher zones of inhibition compared with a commercially available gentamicin sulphate cream against S. aureus, E. coli, S. typhi and P. aeruginosa, while K. pneumoniae was mildly susceptible. Compared with the rest of the formulations, patches of PURASORB ® PL 32 exhibited the best stability, tolerability on rat skin and bioactivity. This study has shown that transdermal patches of PURASORB ® PL 32 represent an alternative delivery system for gentamicin for treatment of infections caused by gentamicin-susceptible micro-organisms.

Development of controlled release silicone adhesive&ndash;based mupirocin patch demonstrates antibacterial activity on live rat skin against <em>Staphylococcus aureus</em>

“…Gentamicin can be used as a comparison to MP due to their similarity in the mode of action, that is, both of them inhibit protein synthesis inside the bacteria. 26 , 27 This method helps to evaluate the antimicrobial activity of drugs such as MP and gentamicin against S. aureus , which leads to determination of the antimicrobial susceptibility of patches.…”

Nanoparticles for Dermal and Transdermal Drug Delivery

“…Technologies for formulation change provide the benefit of improving pharmaceutical product efficacy and safety as well as patient convenience; these technologies provide a relatively simple approach to creating new pharmaceuticals compared with new drug discovery because the active compounds used in the formulation have already been approved [29][30][31]. Nnamani et al [32] developed and evaluated the antimicrobial activities of an alternative non-invasive, convenient and cost-effective transdermal drug delivery system (TDDS) containing gentamicin in biodegradable polyester-based matrices. Other drugs which have been formulated for dermal and transdermal delivery are nitroglycerin, nicotine, scopolamine, clonidine, fentanyl, 17-β-estradiol, testosterone, Boswellic acid (Boswellia serrata) and curcumin (Curcuma longa).…”

Gentamicin nanogel films based on Carrageenan-Prosopis africana for improved wound healing

“…Our earlier work demonstrated the possibility of administering GEN as a fast-release topical agent (microgels) using an optimized nanostructured lipid carrier (NLC) regimen with excellent microbial growth inhibition [12]. Therefore, innovative wound dressing relies on good hydration as the single most important external factor responsible for optimal wound healing [17][18][19]. Healing under wet and moist environments has been clearly demonstrated to be significantly faster than under dry conditions [18].…”

“…The optimum wound healing environment is intermediate gelatinous between moist and dry, as seen in highly vapor-permeable dressings [1,20]. Some mechanisms attributed to this improved wound healing include increased partial pressure of oxygen, preferred migration of epidermal cells over moist wound surfaces than under dry scabs, preservation of growth factors, and presence of proteinases in fluid exudates [19]. Increased moisture impedes capillary activity and reduces hyperemia and collagen deposition.…”

“…In skin delivery, flux across the skin is usually dependent upon skin hydration, partitioning, transport, and concentration gradient across the skin [12, 16-19, 23, 24]. Hydrogels are crosslinked hydrophilic polymers, highly swollen but not soluble in the surrounding medium [12,[16][17][18][19], while films and/or patches are dressings that release the drug from a reservoir through a microporous membrane into the skin [25]. To strike a reasonable balance between the benefits of the breadth of activity of gentamicin and its rapid bactericidal activity, especially in bloodstream infections, versus the toxicity limitations with prolonged use, we report here an alternative low dose gentamicin regimen for cutaneous wound dressing.…”