Resveratrol loaded self-nanoemulsifying drug delivery system (SNEDDS) for pancreatic cancer: Formulation design, optimization and in vitro evaluation

Abstract

Pancreatic cancers are mostly inoperable and have a low survival rate. Nanomedicine has provided some promise in overcoming some major hurdles in pancreatic cancer. Meanwhile, resveratrol (RESV) has been reported to be useful in pancreatic cancer therapeutics. Therefore, the purpose of the study was to develop SNEDDS formulation of RESV for therapeutic application in pancreatic cancer therapy. Capryol 90, Cremophor RH, and Transcutol P were selected as the oil, surfactant, and co-surfactant respectively after preliminary studies. From the pseudo-ternary phase diagram, the surfactant:co-surfactant mixture (Smix) ratio of 3:1 was found to be most suitable for the formulation of SNEDDS. A central composite rotatable design (CCRD) was employed for studying the effect of volumes of oil and Smix on PS and PDI of globules formed from the SNEDDS. For this purpose, the Oil:Smix ratio of 1:4 was chosen for the central point in the design. The results of CCRD showed that a higher volume of oils results in a higher PS and PDI. Similarly, a higher volume of Smix resulted in a lower PS and PDI. The SNEDDS formulation for characterization was chosen based on the particle size (PS), polydispersity index (PDI), and thermodynamic stability. The TEM images revealed uniformity in size and morphology of the formed droplets. Meanwhile, the in vitro RESV release was rapid from RESV-SNEDDS. The cell viability studies, change in mitochondrial membrane potential (MMP), COX-2 and NF-kB levels, and the wound scratch method showed enhanced cytotoxicity of RESV-SNEDDS compared to RESV alone. Overall, the formulation of RESV into SNEDSS was proved to be a promising approach for overcoming the therapeutic hindrances related to pancreatic cancer.