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8 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m Developing Technologies A lbumin, the most prevalent protein found in blood plasma (1), is an emerging drug-delivery tool that has been found to be versatile and effective. Albumins can be used in drug formu- lation because they have been shown to stabilize and extend the shelf-life of the end product. Furthermore, albumins, both naturally occurring and engineered, can be used to extend the half-life of a drug. The accumulation of albumin at inflamed and malignant tissues is thought to involve the enhanced permeability and retention (EPR) ef- fect, according to Dr. Darrell Sleep, chief scientific officer, Albumedix, a biotherapeutics company specializing in albumin-based products and technologies for advanced drug, cell, and vaccine formulation, and drug delivery. Extensive neovascularization combined with a leaky capillary network and impaired lymphatic drainage in inflamed and malignant tissues results in EPR. Consequently, albumin and other plasma proteins accumulate at these sites and are subsequently catabolized by tumors, providing nutrition and energy to the fast-growing tumor, Sleep says. This knowledge can be applied to the development of advanced cancer therapeutics, including biobetters. "Knowing that albumin possesses a natural free thiol conjugation site, CytRx Corp. [a clinical-stage biopharmaceutical company focused on new cancer therapeutics] is developing aldoxorubicin, a biobetter of Doxil (doxorubicin), as a prodrug conjugated in vivo to albumin's single free thiol and incorporating a pH-sensitive linker designed to release the doxorubicin at the tumor. By combining the extended circulatory half-life achieved by conjugation to albumin with albumin's ability to accumulate at tumors and a release mechanism, aldoxorubicin is able to avoid the liver toxicity associated with doxorubicin," Sleep says. As one example of an albumin-based formulation, aldoxorubicin is being evaluated in ongoing clinical trials for the treatment of multiple Albumin Attachment Can Make Better Biobetters Feliza Mirasol Naturally occurring and engineered albumins are being explored as a tool to enhance the stability of drugs, including biologics, and extend shelf-life. JARUN ONTAKRAI/SHUTTERSTOCK.COM