Development and Characterization of In Situ Self-Assembly Nanoparticles for Oral Tissue-Targeting Delivery

Purpose: Tissue-targeting delivery system is an advanced method that improves drug concentration in tissues of interest and minimizes systemic toxicity. Drugs are encapsulated in a carrier and will be released at the site of action. Up to now, very few studies have reported on oral formulations of tissue-targeting delivery systems. Oral dosage form is preferred for the ease in administration and increased patient compliance. The objective of this study is to develop an orally administered nanoformulation that can deliver drug to targeted tissues using the in situ self-assembly nanoparticle (ISNP). Methods: Docetaxel (DTX), an anticancer agent, was used as a model drug for this study. DTX ISNP granules were prepared using surfactant, lipid, solid carrier and DTX. Long term stability of the granules was characterized in term of particle size, drug loading, entrapment efficiency and solid structure using particle size analyzer, HPLC and differential scanning calorimetry (DSC). Particle size stability in simulated physiological environment (2 hours in pH 1.2 followed by another 3 hours in pH 6.8) were studied. In-vitro release of DTX from NPs were also measured using HPLC. After oral administration of DTX ISNP granules, DTX concentration in plasma and tissues of rats were measured using LC-MS. Results: Average size of DTX ISNPs were around 187 nm with narrow distribution and polydispersity index in-vitro release study, up to 20% of DTX was released from NPs after 20 minutes. Plasma concentration of DTX fluctuated throughout the study without significant difference between DTX ISNP granules and DTX powder. However, compared to DTX powder, DTX ISNP granules remarkably increased drug concentrations in liver, lung and kidney at 1 hour after oral administration. Conclusions: The results demonstrated that ISNP nanotechnology has the potential applications in developing an oral formulation that selectively delivers the drugs to the targeted tissues.