Introduction/Background Cervical cancer (CC) is described as cancer that occurs in the cells located in the cervix. Each year, more than 500,000 women are diagnosed with CC and the disease results in over 300,000 deaths across the world. Infection by high-risk oncogenic subtypes of human papillomavirus (HPV); HPV16 and HPV18, is the cause for almost all cases of CC. In developed countries, CC incidence and mortality have more than halved over the past 30 years as they were able to establish successful national HPV screening and vaccination programs. However, this disease remains persistent and has become one of the leading causes of death among women in developing (low to middle-income) countries; mostly in African countries. Adapting to low resources, developing countries have practiced a feasible and cost-effective solutions with the screen and treat approach instead. Screening usually involves visual inspection with acetic acid (VIA) or Lugol’s iodine (VILI) that gives immediate results, facilitating instantaneous treatment strategies and prevents loss to follow-up. Treatments includes loop electrosurgical excision procedure (LEEP), cryotherapy or cold-knife conization. This research proposes the development of a self-administered chemotherapeutic vaginal tablet formulation that would complement these current treatment strategies.
Methodology The bilayer tablets were prepared one layer at a time, using a single punch direct compression machine. Tablets were then evaluated using the pharmacopeial guideline that include tablet uniformity, hardness, friability and content uniformity. Swelling test was performed by simple immersion of the tablets in dissolution medium for 24 hours, the tablet’s weight before and after were recorded. The drug release profile was evaluated by in vitro drug dissolution test using the USP paddle method in 2% aqueous sodium dodecyl sulphate (SDS) solution; maintained at 100rpm, 37±1°C and in sink conditions. All samples were measured spectroscopically. Cell viability after treatment with the drugs was determined using the MTT assay on Ca-ski cells.
Results Results showed that the tablet of this combination are uniform and durable in compliance to pharmacopeial standards, a swelling study shows promising potential for mucoadhesion and has an extended in vitro drug release profile over 72 hours. In vitro cell culture with Ca-Ski cells however, did not show a synergistic effect but only a small additive effect was observed.
Conclusion A vaginal tablet offers an easy application and direct localized access to the cervix; adjacent to the cancerous tissue. The advantages of vaginal drug delivery include (i) bypassing hepatic first pass-effect; (ii) low systemic drug exposure; and (iii) higher bioavailability. A bilayer tablet provides an opportunity to deliver two active pharmaceutical ingredients (API) simultaneously for a synergistic pharmacological effect. Additionally, the different layers physically avoid chemical incompatibilities. Chitosan and polyacrylic acid are the polymers employed for their mucoadhesive property. These polymers also provide an extended and a controlled drug release rate. 5-fluorouracil (5FU) a drug developed and used for the treatment of cancer for more than 50 years was selected as the primary API. Cell studies showed the first combination formulated; 5FU and disulfiram did not show a synergistic effect. Other API will be investigated in combination with 5FU in order to achieve the synergistic effect desired.
Disclosures The authors declare no conflict of interests.
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