Encapsulation and Systemic Delivery of 5-Fluorouracil Conjugated with Silkworm Pupa Derived Protein Nanoparticles for Experimental Lymphoma Cancer.

Protein-based drug delivery systems have an edge over conventional drug delivery systems due to their biodegradability, non-antigenicity, and excellent biocompatibility to improve the therapeutic properties of anticancer drugs. This study describes the increased anticancer efficacy of 5-fluorouracil (5-FU) conjugated with silkworm Bombyx mori pupal biowaste derived nanoparticles. Here, we have checked the toxicity of pupa-protein nanoparticles (PpNps) and their potential as a carrier for anticancer drugs. PpNps were prepared by a desolvation method which resulted in a uniform particle size of 162.7 ± 2.9 nm. The 5-FU loaded PpNps were formulated and characterized. The drug content of the developed 5-FU conjugated nanoparticles was evaluated by HPLC analysis. The entrapment efficiency and loading capacity of 5-FU were analyzed by HPLC and determined to be 93% and 88.6%, respectively. The release studies showed the biphasic release of 5-FU at pH 7.4 where rapid drug release was achieved for first 30 min, followed by a sustained release of 5-FU from the developed Nps achieved for the next 8 h. Mice with developed ascites tumors were intraperitoneally treated with 5-FU-PpNps and sacrificed. There was a significant increase in total red blood cells and hemoglobulin in 5-FU-PpNps treated mice, whereas a significant decrease in white blood cells which indicated the reduced inflammation of cancer. Subsequently, 5-FU-PpNps decreased the tumor volume and tumor cell viability, which proved its cytotoxic property to cancer cells. This study presents a novel approach to derive B. mori pupal protein nanoparticles, which can be safely used for cancer drug delivery.

Lacidipine self-nanoemulsifying drug delivery system for the enhancement of oral bioavailability.

Low bioavailability of Lacidipine (LD), an calcium channel blocker pose many challenges in the treatment of hypertension. The objective of this study was to formulate and characterize LD self-nanoemulsifying drug delivery systems (SNEDDS) to improve oral bioavailability of the drug. Formulations were evaluated for globule size, surface morphology, emulsification time, cloud point, drug content, in vitro dissolution, ex vivo permeation, stability and oral bioavailability studies. Captex 810D, TPGS, Tween-60, Transcutol P and PEG 400 was selected based on the solubility study results. The optimized SNEDDS readily gets nanoemulsified at 37 °C with droplet size of 41 nm when mixed with 200 times of its water. Transmission electron microscope photographs confirmed the spherical shape of the globules. In vitro dissolution of SNEDDS showed more than 80% of drug release within 15 min. The ex vivo permeation of LD from SNEDDS is 4.8- and 9-fold higher compared to pure drug in the absence and presence of verapamil respectively. The stability study of the SNEDDS confirmed no environmental effect on the physical nature and drug content. Oral bioavailability of SNEDDS is 2.5 times higher than marketed tablet. The results suggest that, the SNEDDS formulation can be used as a possible alternative for the traditional oral formulations of LD to improve its oral bioavailability.