Self-emulsifying Drug Delivery System for Oral Anticancer Therapy: Constraints and Recent Development

Abstract

Abstract: Oral anticancer therapy faces several drawbacks of low aqueous solubility, poor and irregular absorption from gastro-intestinal sites, high first-pass metabolism, food-influenced absorption, non-targeted delivery, severe systemic and local adverse effects, etc. Enhancement of oral bioavailability could reduce the drug load and associated adverse effects. Self-emulsifying drug delivery systems (SEDDS) can enhance in-vivo solubility and drug absorption from the gastrointestinal tract, bypass liver metabolism by lymphatic absorption and inhibit efflux transport. All these phenomena ultimately result in improved oral bioavailability. Anticancer drug delivery using the SEDDS has shown promising results for bioavailability and pharmacodynamic response. A handful number of researches have produced evidence of the successful loading of anticancer agents in SEDDS-based formulations. Various potent and established chemotherapeutic agents such as docetaxel, paclitaxel, etoposide, 5 Fluorouracil, doxorubicin etc. have been successfully formulated and evaluated. Improved bioavailability and reduction of dose might be possible by SEDDS. It could be effective for low-dose drugs. But, excessive surfactant-cosurfactant concentration, lacking predictive in-vitro models and adequate IVIVC, unavailability of toxicity data are certain challenges for future researchers. To date, no clinical trials have been recorded with anticancer drug loaded SEDDS. To avail the benefits of anticancer SEDDS, overcoming the challenges and further progression to clinical studies are required. Methods: Hospital based retrospective, observational study in which all the confirmed cases of CSC (272) seen between 2010 and 2019 were included. Supplementary data was collected on follow up visits or through telephonic calls. Results: The male: female ratio was 17:1; low socio-economic status was (155; 73.45%), and occupations such as drivers (61; 28.9%) and outdoor laborers (59; 27.96%) were the most commonly affected. The majority (78.05%; 185) were single expatriates. Financial worries (105; 50.72%) constituted the leading cause of stress. The usage of corticosteroids (83; 30.51%), nasal decongestants (14.70%) or both (17; 6.25%) within one year was common; mostly (82; 30.14%) for rhinitis/respiratory states, though grossly under-recognized. Muscle relaxants and psychotropic medications were the other major medications used by 24 (8.82%) and 25 (9.19%) cases prior to CSC. Seven of 15 women had at least one condition that alters the endocrinal milieu: Pregnancy (3), recent child birth (1), erratic oral contraceptive intake (1), menopause with liver dysfunction (1), hormone replacement therapy for menopause and endometriosis (1), ovarian cyst and infertility (1) hypothyroidism (3), and Cushing syndrome (1). Chronic/ recurrent forms were seen in 31.08%. There were too few glaucoma patients despite both CSC and glaucoma being common among our patients.