A novel combinatory paradigm for chronic hepatitis C treatment using liver-targeted carrier erythrocytes co-encapsulated with interferon alpha-2b, ribavirin and boceprevir

"nDespite outstanding developments in medical knowledge and technologies, Hepatitis C virus (HCV) affecting almost 180 million people worldwide, is still described as "a serious global health crisis" and its standard of care (combination therapy with pegylated interferon alpha and ribavirin) is just effective in at most 50% of all patients. This suboptimal efficacy and apparent side effects underscore the need for "new anti-HCV agents", "novel combination strategies" and "smart delivery systems". As a response to the urgent need for new anti-HCV drugs, specifically targeted antiviral therapy agents for HCV (STAT-C) has gained many interests these years. Considering the obligation of multidrug therapy in HCV infection and the results of clinical trials, STAT-C will probably supplement interferon/ribavirin combination. Boceprevir as a HCV protease inhibitor is among the most widely studied STAT-C compounds with promising results in clinical trials. Thus, its combination with current double therapy paradigm would be an alternative combination strategy in the treatment of hepatitis C. On the other hand, drug carriers has now evoked much attentions as new trends to increase the efficacy of available therapies by protecting the therapeutic agents from unwanted reactions and/or targeting them directly to their site of action. Carrier erythrocytes are among the most widely studied cellular and particulate carriers suitable for targeted delivery of various drugs to reticuloendothelial system organs like liver, but, with no report about their application for HCV-targeted therapy. Since the majority of recent efforts are focused on new agents' discovery/development and alternative combinations and no reports are available on targeted delivery of double and/or triple drug combinations directly to the liver, an idea has been raised that combination of all 3 approaches mentioned earlier (a completely combinatory paradigm addressing all 3 mentioned needs by one system i.e. the "new anti-HCV agents" in a "novel combination" delivered to its site of action via a "smart delivery system") may have more promising results and reduce the shortcomings of recent approaches. This idea has led us to hypothesize that carrier erythrocytes co-encapsulated with interferon alpha-2b, ribavirin and boceprevir by means of hypotonic preswelling encapsulation method with post-loading modifications of obtained drug-carriers, could be an appropriate liver targeted-triple combination therapy for HCV particularly in difficult patients (non-responders, co-infected patients with HIV and the one