Vesicular approach for anti-cancer drug delivery: formulation and evaluation

Abstract

The research in localized delivery of anti-cancer drugs directly to tumor sites has evoked a considerable interest recently due to obvious advantages over conventional routes. Localized drug delivery is a way to deliver the drug from a dosage form to a particular site in the biological system, where its entire pharmacological effect is desired. Local administration of chemotherapeutic agents at the tumor site is also thought to enhance the chemo-responsiveness by exposing tumors and adjacent metastases to high drug concentration while reducing its systemic exposure. Two approaches have been widely studied for localized delivery of anti-cancer drugs. First is the dermal drug delivery and second is subcutaneous (SC) and intratumoral administration of hydrogel formulation. In the present study, both approaches have been selected for localized delivery of paclitaxel. In current clinical practice, paclitaxel is administered by intravenous route. The i.v. administration of paclitaxel distributes the drug into some vital organs like heart, liver and kidney leading to very severe cardiotoxicity, myelosuppression and mucositis. In addition to this, very little amount of drug reaches the target tumor tissues like breast and skin cancers, resulting in very poor therapeutic efficacy. However, the usefulness of paclitaxel for the therapy of skin cancer is limited due to the serious adverse effects associated with the i.v. administration. In spite of the obvious advantages associated with the cutaneous delivery of paclitaxel, there is no topical formulation commercially available. Breast cancer treatment also requires localized delivery of paclitaxel. However, high molecular weight of paclitaxel makes it difficult for it to penetrate through a dense and hydrophobic stratum corneum at a rate sufficient to achieve therapeutic efficacy. One strategy to achieve the high local drug concentration at tumor vicinity and also sustain the drug release is to encapsulate paclitaxel in elastic liposomes.