Pharmacotherapeutic approaches for transportation of anticancer agents via skin

Abstract

Cancer is the largest family of diseases that involve abnormal uncontrolled cell growth which metastasizes to other parts of the body. The most common type of cancers includes lung, liver, colorectal, prostate, stomach, breast and cervical cancer with skin cancer excluding melanoma (contribute up to 40% of the cases). The conventional treatment approaches like surgery, chemotherapy, etc., have several side effects such as severe inflammation and pain. Hence, pharmacotherapeutic approaches of antineoplastic agents can be advantageous for treating various forms of cancer through the skin. Novel transdermal techniques and preparations have been emerged to overcome the limitations of skin and to penetrate inside the cancerous cells by transporting through the deeper tissues of the skin. The transdermal penetration of drugs using different formulations such as nanocarriers, physical penetration enhancement techniques, chemical penetration enhancers and newer technologies such as gels, dendrimers, needle-free injection jet etc., show improved patient compliance, abolition of scars and economic value. The topical delivery of antineoplastic agents is an attractive choice for increasing site-specific delivery, reducing side effects and improving therapeutic effects. The objective of this review is to present insights into pharmacotherapeutic techniques, which can be used for transdermal delivery of anticancer agents through skin due to its potential to create a new frontier in treatment of cancer.

Skin cancer biology and barriers to treatment: Recent applications of polymeric micro/nanostructures

“…Usually, AK lesions form excessive keratin, resulting in the thicker SC layer and consequently a stronger barrier for NPs entry. Thus, NPs employed against AK require proper designing to reach the deep epidermal layers, where the langerhans cells are present, to show immune response [105] . A layer below the SC is an epidermal layer called as viable epidermis and it reaches down to the thin basal layer dermal-epidermal junction [106] .…”

Nanotechnology approaches in the current therapy of skin cancer

“…Generally, AK lesions produce excessive keratin, making the SC layer thicker and consequently a more difficult barrier to penetrate. Therefore, NPs used against AK need to be properly designed to pass through the SC and reach the deeper epidermis layer, where the Langerhans cells are located, to exert immune responses [34].…”

“…NP features, such as particle size and particle size distribution, shape, surface charge, surface function, and chemical nature, can be designed to fit the therapeutic approaches [65]. Thus, well-designed systems should be able to (i) solve drug solubility issues, mainly those related to highly hydrophobic drugs, (ii) encapsulate the anticancer agent in its internal structure to improve drug stability by chemical or physical means, (iii) provide delivery of encapsulated drug by controlled or sustained release rates and (iv) reduce skin irritation by avoiding direct drug-skin contact [34]. Additionally, when systemically administered, NPs should have the ability to (i) overcome the lymphatic drainage system, (ii) remain for a long time in the bloodstream and (iii) reach the therapeutic site at effective doses.…”

Formulations Based on Drug Loaded Aptamer-Conjugated Liposomes as a Viable Strategy for the Topical Treatment of Basal Cell Carcinoma—In Vitro Tests

“…In cases where the cancer has spread to large areas of the body, topical administration of anticancer drugs is recommended to reduce primarily the cost of surgery and unwanted scars and also to increase patient compliance. Topical administration of anticancer drugs is an easy and effective method to reduce side effects and increase drug targeting and therapeutic benefits [8,9]. At the present, two types of drugs, formulated as creams or ointments, are used almost exclusively: imiquimod (Aldara) [10], for immunotherapy, and 5-fluorouracil (5-FU) (Carac [11], Fluoroplex [12] and Efudex [13]), for skin cancer chemotherapy, with a cure rate of around 80%.…”