Designing the biocompatible chitosan polymeric micelle for transferring curcumin as a promising natural anti-cancer therapy for basal cell carcinoma

Cancer is one of un-infectious disease that has high fatality and high mortality rate. One of common cancer in Indonesia is skin cancer, specifically Non-melanoma Skin Cancer/NMSC. Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC) are two most common type of NMSC. The most frequent case in Indonesia is BCC with a percentage of 66.9%. Skin cancer treatments nowadays have been focused on exploring the natural medicine. Natural medicine has some beneficial compared to the synthetic drugs, one of them is the biocompatibility and nontoxicity properties. One of the potential natural medicines for BCC is curcumin isolated from turmeric (Curcuma Longa).

Curcumin has strong anti-inflammatory activity and can be potentially used as cancer symptoms treatment. Curcumin can also act as an essential antioxidant that limits the damage of cells and organs caused by oxidative stress. As an effective anti-cancer treatment, Curcumin should reach the basal epidermis of the skin to target the BCC. Therefore, Curcumin needs to be formulated into a potential carrier that can enhance its bioavailability and overcome its limitations, one of them by using polymeric micelle.

Polymeric micelles are a promising material that can act as a carrier for delivering chemotherapeutic agents suffer from low solubility and poor bioavailability properties. The prior research revealed that polymeric form limits the access of active agent to enter the systemic circulation which can be the appropriate properties for the treatment in the local skin area only. Therefore, Polymeric micelle can be a potential drug delivery system for transferring an anticancer drug for skin cancer treatment.

Various amphiphilic polymers have been constructed to form a micelle. Chitosan-based polymeric micelle is one of the most popular research projects nowadays as a carrier for drug delivery due to its biocompatibility, biodegradable and low toxicity. Chitosan can react to other material by ionic interaction. To form a potential micelle above CMC, chitosan should be combined with material that has hydrophobic characteristic.

The goal of this study is to develop and characterize an optimized and physically stable polymeric micelle containing curcumin. The polymeric micelle than be evaluated of their efficacy and their biodistribution profile in skin layer.

In general, the steps of research will be conducted as follows:

a. Synthesis of Curcumin loaded Chitosan-Based Polymeric Micelle

- Synthesis of Chitosan-lipoic acid di-block copolymer using ionic interaction between amino group of chitosan and the carboxylic group of lipoic acid in the presence of EDC-NHS

- Self-assembly of Chitosan-Based Polymeric Micelle by dispersing copolymer in distilled water followed with probe-type ultrasonic treatment

- Curcumin loading into the polymeric micelles using dialysis method

b. Characterization of chitosan-based polymeric micelles

- Determination of CMC of polymeric micelles by dye solubilization method using pyrene as fluorescent probe

- Particle size and zeta potential measurement using dynamic light scattering

- Morphological evaluation using TEM

c. Development and characterization of micelle gel formula

d. In vitro and In Vivo Evaluation