Abstract 1741: Single protein encapsulation as a drug delivery platform for developing efficacious anticancer therapeutics
Authors: Yu C. J. 
Published: September 2020

Small molecule anticancer drugs are potent and effective agents against a variety of malignancies. However, severe side effects are often associated with their application due to systemic toxicities caused by their indiscriminate infiltration into normal tissues, organs, and cells. Using natural human serum albumin (HSA) as the carrier, Sunstate Biosciences LLC has recently invented the SPE platform for anticancer drug formulation. The SPE technology employs only FDA-approved components to form HAS-encapsulated product SPE-DRUG. Unlike HSA nanoparticles that usually contain a number of HSA molecules through chemical conjugation/crosslinking or aggregation, the SPE-DRUG has a single HSA molecule that encloses a variable number of DRUG molecules via noncovalent interactions, and importantly it retains the molecular size of HSA. Both the DRUG/HSA ratio and the binding strength can be tuned precisely to allow controlled release of the DDRUG during circulation. The SPE platform is versatile and can be applied to the formulation of a variety of single- and multiple-anticancer drugs.

We have successfully prepared the following formulated drugs: SPEDOX, SPEEPI, SPEDAU, SPEMIT, SPEIDA, SPEVIC, SPEVIB, SPEVIL, and SPEDOC. All SPE-DRUGS are highly water soluble to form clear and stable solutions. Their size distribution profiles determined by DLS are almost identical to that of HSA, suggesting no disruption of the structure and properties of native HSA. Pharmacokinetic properties of SPEDOX were evaluated. Mouse heart tissues harvested at 2/24 h were analyzed. Antitumor efficacy using a breast cancer model (MDA-MB-231) were also evaluated at various doses. Key findings include 1) ~ 47 fold increase in AUC, 2) ~ 4-8 fold decrease in free DOX in the mouse heart tissue, and 3) fivefold increase in MTD and substantial enhancement of tumor efficacy (34/88% TGI for DOX/SPEDOX).

Drug release studies in pH 7.4 PBS and pH 5.2 acetate buffer revealed that SPEDOX, SPEEPI, SPEDAU, SPEMIT, SPEDA, SPEVIC, SPEBIB, SPEVIL released their drug molecules twice as fast in acetate buffer than in PBS. The enhanced drug release in acidic media provides a possible mechanism for targeting tumors due to their acidic environment, thereby leading to increased antitumor efficacy. Separate antitumor efficacy studies with SPEMIT also showed enhanced antitumor efficacy against MDA-MB-231 (16/56% TGI for MIT/SPEMIT).

In conclusion, Sunstate Biosciences' novel SPE drug formulation and delivery platform can significantly enhances the pharmacokinetics and antitumor efficacy and, at the same time, reduces the side effect of the drug, leading to increased therapeutic indexes. SPE-DRUGS have the potential to revolutionize cancer treatment regimens and save lives of difficult-to-treat cancer patients.

Citation Format: C. J. Yu. Single protein encapsulation as a drug delivery platform for developing efficacious anticancer therapeutics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1741.