Tuesday, May 31, 2016

PLGA-PEG-PLGA investigated for intratympanic delivery of antiviral medicines as cytomegalovirus treatment

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable block copolymers including PLGA-PEG-PLGA. This biodegradable thermogel is a free-flowing solution at room temperature and stiffens to a gel when warmd to body temperature. One common cause of hearing loss is a cytomegalovirus (CMV) which is a viral infection that leads to progressive deterioration of the inner ear and eventual hearing loss in children. The two most common antivirals used to treat this (Ganciclovir and Cidofovir) are effective against the virus but have significant toxicity when delivered systemically especially towards kidneys. One way to avoid system side effects is to provide for a localized delivery of the medicine to the exact location needed so that overall systemic dose is very low while the local dose is about the therapeutic threshhold. Recently, researchers in Cincinnati have combined these antivirals with thermogelling PLGA-PEG-PLGA along with anti-inflammatory dexamethasone to generate a system that can be injected into the intratympanic space and deliver these medicines there. This research may be useful for treating a disease which leads to hearing loss in the future. Read more: Sidell, Douglas, Jonette A. Ward, Angad Pordal, Carson Quimby, Michel Nassar, and Daniel I. Choo. "Combination therapies using an intratympanic polymer gel delivery system in the guinea pig animal model: A safety study." International journal of pediatric otorhinolaryngology 84 (2016): 132-136. http://www.sciencedirect.com/science/article/pii/S0165587616001038


“Abstract: Objectives: High dose antivirals have been shown to cause hearing loss when applied via the intratympanic route. The aim of this study was to determine if a combination therapy using dexamethasone (DXA) with either Cidofovir (CDV) or Ganciclovir (GCV), in solution or in PLGA-PEG-PLGA (PPP) hydrogel, is innocuous to the inner ear. Methods: Cytomegalovirus (CMV)-free guinea pigs were separated into four principal study groups and treated via intratympanic injection (IT) of CDV/DXA solution, CDV/DXA Hydrogel, GCV/DXA solution and GCV/DXA hydrogel. Hearing thresholds were evaluated with pretreatment ABR and post injection weekly ABRs for a total follow up of 28 days. Temporal bone tissue was harvested and stained with Hematoxylin and Eosin for histologic analysis. Results: ABR analysis revealed that GCV/DXA in solution and in hydrogel led to a mild hearing loss at days 7–21 but returned to baseline by day 28 When administered via PPP hydrogel, CDV/DXA demonstrated mild persistent hearing loss at 32 kHz at 28 days. An inflammatory response was identified in the cochlear specimen of the CDV/DXA/PPP hydrogel group, in concert with mild hearing loss, at days 21 and 28. Conclusion: Results of this study support the safe intratympanic use of higher concentrations of antivirals when combined with DXA, both in solution and when applied via PPP hydrogel. Keywords: Antiviral; Hydrogel; Intratympanic; Dexamethasone; Cidofovir; Ganciclovir”
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