(T1230-02-12) Non-haemolytic Nanoemulsions Development and Characterization for Novel Anti-prostate Cancer Compound PC257

Purpose: According to the National Cancer Institute, there were approximately 268,000 new cases of prostate cancer in 2022, which accounts for 14% of all new cancer occurrences. Of those cases, there was a 5.7% death rate. Along with early detection, the numerous treatment options which include targeted, or precision therapy give patients the opportunity to fight prostate cancer with less chances of impotence and incontinence. Targeted treatment regulates the proliferation and spreading of cancer cells by targeting a specific protein. Compound PC257 specifically targets the FKBP52 protein. This compound shows inhibition behaviors toward the Androgen, Glucocorticoid, and Progesterone receptors for FKBP52. PC257 has a molecular weight under 500g/mol and possesses a LogP value of 3.45, pKa value of 11.8, one hydrogen donor and nine hydrogen acceptors. Based on Lipinski’s rule of five, this compound should have a good drugability. Upon preformulation study, howere, its solubility was found to be very low and solubility is a significant factor in determining the bioavailability of a drug.

Methods: A nanoemulsion therefore was developed due to its capability of increasing the drug's bioavailability while efficiently delivering it to the targeted site. The nanoemulsion size range tends to fall between 2-200nm. And choosing to formulate non-haemolytic intravenous nanoemulsion can achieve the targeted effects safely.

Results: A fast and reliable UPLC method was developed to quantify PC257. The nanoemulsion formulation was prepared by a low energy stirring/heat inversion method with a targeted raised temperature range of 85 to 90 oC to combine transcutol (solubilizer), labrafac (oil), and tween 80 (surfactant) to create the oil phase and water to create an aqueous phase. PC257 was added at various phases of the formulation to achieve optimal drug level concentrations. Characterization and analysis executed via Nanodrop UV-Vis, Malvern Zeta Sizer, and Acquity UPLC. Zeta Sizer data for unfiltered and filtered emulsions both have mean PDI 0.289 standard deviation +/- 0.034, Z-Average 210.33 d.nm +/- 25.53, Zeta potential -20.02mV +/- 5.27. NanoDrop UV-Vis shows absorbance of compound at 280 to 300nm range. And UPLC analysis showed a concentration range of 47 to 60% and encapsulation efficiency mean range of 44 to 51%.

Conclusion: By developing non-haemolytic nanocarriers, poorly soluble anti-cancer drugs are more effective in targeting tumor sites. These routes of administration address improved bioavailability, multi-drug resistance and provide less invasive treatments.

Acknowledgements: National Institute on Minority Health and Health Disparities of the National Institutes of Health (NIH) under award number 2 U54 MD007605-27A1.