Drug delivery to tumours: recent strategies

Abstract

Despite several advancements in chemotherapy, the real therapy of cancer still remains a challenge. The development of new anti-cancer drugs for the treatment of cancer has not kept pace with the progress in cancer therapy, because of the nonspecific drug distribution resulting in low tumour concentrations and systemic toxicity. The main hindrance for the distribution of anti-cancer agents to the tumour site is the highly disorganized tumour vasculature, high blood viscosity in the tumour, and high interstitial pressure within the tumour tissue. Recently, several approaches such as drug modifications and development of new carrier systems for anti-cancer agents have been attempted to enhance their tumour reach. Approaches such as drug delivery through enhanced permeability and retention (EPR) effect have resulted in a significant improvement in concentration in tumours, while approaches such as drug-carrier implants and microparticles have resulted in improvement in local chemotherapy of cancer. This review discusses different strategies employed for the delivery of anti-cancer agents to tumours, such as through EPR effect, local chemotherapeutic approaches using drug delivery systems, and special strategies such as receptor-mediated delivery, pH-based carriers, application of ultrasound and delivery to resistant tumour cells and brain using nanoparticles.

Enhancement of intratumoral cyclophosphamide pharmacokinetics and antitumor activity in a P450 2B11-based cancer gene therapy model

“…Physiological conditions associated with solid tumors often lead to poor drug uptake, 44,45 which in the case of prodrug activation gene therapy may translate into inefficient prodrug activation. Presently, 4-OH-CPA production by P450 2B11-expressing 9L tumors was not saturated at a prodrug dose corresponding to a C max (CPA) of B200 mM, that is B3 times the observed K m of P450 2B11, suggesting inefficient penetration of CPA, despite the good vascularity of 9L tumors.…”

Folate and iron difunctionalized multiwall carbon nanotubes as dual-targeted drug nanocarrier to cancer cells

“…Although great improvements have been made to the application of f-CNTs as drug carriers, there are two major obstacles blocking further use of the f-CNTs in cancer chemotherapy. The first one is the non-specific toxicity of anticancer agents to the proliferation of normal cells, while the second one is the poor potency of the anticancer agents [18,19]. To achieve the discrimination of the natural and the cancerous tissues, the targeting ability is a crucial property for the f-CNTs as drug carriers.…”

Nanotechnology in Cancer Diagnosis and Treatment

“…The altered lymphatic drainage of the tumor contributes to this effect [15]. This type of passive targeting is known as "EPR" (enhanced permeation and retention) [16,17] (Fig. 1).…”