The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the P-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential −14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R² = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10−fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.

Sarfaraz Ahmad1, Mohammad Daud Ali2, Amani Khardali1, Md. Sajid Ali3, Gyas Khan4, Nawazish Alam1, Hilal Thaibah1, Ayesha Khatun5, Tarique Anwer5 and Md. Sarfaraz Alam5 Author informationArticle notesCopyright and License informationCitations 1Department of Clinical Pharmacy, Pharmacy Practice Research Unit (PPRU), College of Pharmacy, Jazan University, Jazan, SAUDI ARABIA 2Department of Pharmacy, Mohammed Al-Mana College for Medical

Self-microemulsifying drug delivery systems (SMEDDS) formulations have emerged as crucial methods for improving the bioavailability of poorly water-soluble drugs. However, they exhibit several limitations, including oxidation of unsaturated fatty acids, restricted lymphatic absorption, handling challenges, in vivo drug precipitation, a lack of predictive in vitro research—and their high surfactant content can cause gastrointestinal irritation. These factors can impede their broader application. Incorporating precipitation inhibitors or polymers within lipid-based formulations helps maintain drug supersaturation after dispersion, thereby reducing exposure variability and enhancing bioavailability. Converting liquid SMEDDS into solid forms also addresses issues related to liquid handling and stability. This review highlights recent developments, such as the use of nanotechnology, innovative excipients, and solidification techniques in the formulation of herbal SMEDDS. It also evaluates their advantages and drawbacks in drug delivery, with a particular focus on key performance parameters like droplet size, zeta potential, and stability. Additionally, self-nanoemulsifying drug delivery systems (SNEDDS) show considerable promise for improving the bioavailability and solubility of poorly water-soluble herbal extracts by encapsulating them in nanoemulsions. In summary, SMEDDS offer a viable oral platform for administering poorly soluble medications and herbal extracts, with the potential to significantly enhance therapeutic outcomes. For wider clinical adoption, however, challenges related to formulation stability, scalable manufacturing, and regulatory compliance must be addressed. Future research should aim to overcome these barriers and expand SMEDDS applications across diverse therapeutic areas.