Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT₁₄) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT₁₄) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT₁₄) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.

Ciprofloxacin (CIP), a potent anti-bacterial agent of the fluroquinolone family, shows poor solubility and permeability, thus leading to the development of intracellular pathogens induced multi-drug resistance and biofilms formation. To synergistically improve the biopharmaceutical parameters of CIP, a hyaluronic acid (FDA approved biocompatible polymer) functionalized self-nano emulsifying drug delivery system (HA-CIP-SNEDDS) was designed in the present study. SNEDDS formulations were tested via solubility, droplet size, zeta potential, a polydispersity index, thermodynamic stability, surface morphology, solid-state characterization, drug loading/release, cellular uptake, and biocompatibility. The final (HA-CIP-SNEDDS) formulation exhibited a mean droplet size of 50 nm with the 0.3 poly dispersity index and negative zeta potential (−11.4 mV). HA-based SNEDDS containing CIP showed an improved ability to permeate goat intestinal mucus. After 4 h, CIP-SNEDDS showed a 2-fold and HA-CIP-SNEDDS showed a 4-fold permeation enhancement as compared to the free CIP. Moreover, 80% drug release of HA-CIP-SNEDDS was demonstrated to be superior and sustained for 72 h in comparison to free CIP. However, anti-biofilm activity of HA-CIP-SNEDDS against Salmonella typhi was higher than CIP-SNEDDS and free CIP. HA-CIP-SNEDDS exhibited increased biocompatibility and improved oral pharmacokinetics as compared to free CIP. Taken together, HA-CIP-SNEDDS formulation seems to be a promising agent against Salmonella typhi with a strong targeting potential.

Over the past several years, employment of multifunctional polymeric excipients-based nanoparticles for controlled and targeted drug delivery of therapeutic modalities to mucosal membrane-based organelles and systemic circulation has gained enormous interest. Because they promise to resolve numerous key therapeutical issues associated with current clinical practice including low treatment efficacy and significant side effects. Potential controlled and targeted drug delivery systems, therefore, should be able to overcome not only extracellular barriers but also intracellular barriers. Extracellularly, targeted nanocarriers ought to provide extended circulation time, selective binding to the targeted mucosal tissues, long residence time at the site of absorption, and controlled drug release. Intracellularly, the targeted nanocarriers should offer cellular uptake, cellular localization, and endosomal release. Hence, this chapter will provide an overview of the unique chemistry of multifunctional polymeric enveloped diverse nanocarriers such as dendrimers, semiconducting polymer dots, quantum dots, carbon dots, and magnetic as versatile platform addressing both extracellular and intracellular barriers.