Super-High Capacity Polymeric Micelles for Cancer Therapeutics…and Few Words about Covid-19 Therapeutics

Abstract: Poly(2-oxazoline) polymeric micelles (PM) display unprecedented high loading with respect to water-insoluble active pharmaceutical ingredients (APIs). This drug delivery platform greatly enhances the solubility and stability of drugs and drug candidates and improves their efficacy and safety in a transformative way. The technology has been validated for more than 20 extremely poorly soluble APIs. The injectable aqueous solutions are readily prepared that are stable and contain up to 50-100 g/L of extremely poorly soluble APIs, at least 10 to 100 times greater amounts than most other solubilization methods. The drug to excipient ratio in poly(2-oxazoline) PM is also 10 to 100 times better than the ratios of excipients in other approaches. One example is a Cremophor- and PEG-free paclitaxel in poly(2-oxazoline) PM. It has demonstrated potential to increase treatment efficacy of cancers by using high-dose therapy and shown superiority in treatment of tumors in animal models when compared to marketed paclitaxels. For many of the drug candidates, poly(2-oxazoline) PM platform represents the only possibility for a parenteral drug application and enables major contribution to patient care. Chemo-sensitizing agents and agents modifying tumor microenvironment in poly(2-oxazoline) PM were shown to improve chemo- and immunotherapy of cancers in both prevalent and orphan diseases in animal models. Poly(2-oxazoline) PM platform allows easy co-formulation of multiple APIs to 1) decrease burden of administering these APIs separately to a patient in combination drug therapy, and 2) improve treatment efficacy by simultaneous delivery of these APIs to biological targets. Superior antitumor activity of PM with co-loaded drugs compared to single drug micelles or their combination was demonstrated. A rational, computer-aided approach to reliable selection of hydrophobic molecules with dramatically improved solubility in poly(2-oxazoline) PM was developed to enhance the throughput and success of formulation development for new APIs. The work has been supported by the United States National Institutes of Health (1U54CA198999).