ABSTRACT
Alkyl cyanoacrylates have been used as surgical materials, in particular as biodegradable tissue adhesives, since the 1960s (Leonard et al., 1966). Since their discovery, the U.S. Food and Drug Administration has approved two monomers, butyl cyanoacrylate (2002) and octyl cyanoacrylate (1998), for human use, which are available on the market as liquid bandaids (Indermil®, LiquiBand®, and Dermabond®). Poly(alkyl cyanoacrylate) (PACA) nanoparticles emerged in drug delivery around 30 years ago (Couvreur et al., 1979). They have since been explored with increasing interest as colloidal drug delivery systems and for targeting of bioactives, including low molecular weight drugs, peptides, proteins, and nucleic acids. The extensive interest in PACA nanoparticles as drug carriers is due to the biocompatibility and biodegradability of the polymer, the ease of preparation of the particles, and their ability to entrap bioactives, including subunit antigens. Many modern drugs are proteins that are susceptible to chemical and enzymatic degradation in the physiological environment and exhibit low bioavailability. They thus require chemical and enzymatic protection, bioavailability enhancement, and even targeting to certain delivery sites. Encapsulation of proteins into PACA nanoparticles may be one way of overcoming some of the challenges in effective protein delivery. However, although PACA nanoparticles have been considered as promising polymeric colloidal drug delivery systems for some time, no product has entered the market. Initial progress has been made in the clinical development of a PACA formulation in cancer therapy. In 2006 BioAlliance Pharma announced clinical phase II/III trials for Transdrug®, doxorubicin (DOX)- loaded poly(isohexyl cyanoacrylate) (PiHCA) nanoparticles suitable for intra-arterial, intravenous (i.v.), or oral administration. However, because of acute pulmonary damage, phase II trials of Transdrug were suspended in July 2008.
