Development Of Oral Dosage Form Containing Phytoconstituents As Adjuvant Or Neoadjuvant Therapy For Malignant Neoplasm

Abstract

Malignant neoplasm or cancer is one of the major causes of higher mortality newlinethroughout the world. Currently, it can be treated by multiple ways, such as newlinechemotherapy, radiotherapy, immunotherapy etc. However, patients under these newlinetherapies usually have a poor prognosis and systemic side effects. Moreover, it may newlinefurther lead to multiple drug resistance. These incidences are due to lack of selective newlinecytotoxicity, inefficient drug delivery to the cancer cells, invasion and metastasis. newlinePhytochemicals have the capability to play an important role in all of these areas. newlineScientific literatures regarding antitumor, antimetastatic, anti-angiogenesis, selective newlinecytotoxicity to a tumor cell, less or absence of cytotoxicity to host cells, chemosensitization, newlineand reversal of drug resistance, immuno-modulatory, the antioxidant newlineactivity of phytochemicals are available. Some of the phytochemicals are in clinical newlinetrials also. Moreover, some of them are a part of our daily diet. Formulation newlinedevelopment studies with such compounds are very less. newlineIt was therefore conceived that a formulation needs to be developed incorporating newlinephytochemicals that can address one or more aspects of cancer and its treatment. The newlineresearch work has been designed to address the challenges mentioned here with an newlineintention to develop and standardize a dosage form with phytochemicals which can be newlineco-administered any of the cancer therapy. So, that multiple biological activities of newlinethese compounds can improve the efficacy of cancer treatment and reduce the odds of newlinethe therapeutic regimen. newlineBy keeping in mind the above statement, curcumin and quercetin was selected as newlinedrugs. To overcome the bioavailability problems piperine was used as bioenhancer. newlinePreformulation studies were carried out. The cytotoxicity of the compounds newlineindividually and in combination was estimated. Based on the combination index value newlinetheir ratio of the drugs was established. Bioavailability problem of curcumin was newlineaddressed and compared. Curcumin and quercetin were encapsulated in lipid vesicles newlineto increase the circulation time and to reduce rapid metabolism. Cytotoxic effects of newlinethe liposomal drugs were estimated. Stability study and acute toxicity study were also newlineperformed. Then the liposomal drugs were filled in capsule and then the capsules newlinewere estimated as per pharmaceutical specification. newlineOn the basis of the experimental work done so far, it can be concluded that an oral newlinedosage form can be successfully prepared with these phytoconstituents, which can be newlineused as adjuvant or neoadjuvant therapy along with conventional anticancer therapy. newlineDue to synergistic activity of these compounds the dose of the synthetic drug can be newlinereduced which may further lead to reduced adverse effect. newlineThis work also creates a vast opportunity to explore the mechanistic approaches of the newlinedrugs as well as to explore the other aspects of the used drugs like inhibition of efflux newlinemechanism, reversal of multiple drug resistant, prevention of recurrence, prognosis of newlinepatients life, etc.