Clinical experience with drug delivery systems as tools to decrease the toxicity of anticancer chemotherapeutic agents

ABSTRACT

Introduction: The toxicity of chemotherapeutic agents, resulting from their low pharmacological index, introduces considerable discomfort and risk to cancer patients. Among several strategies to reduce the toxicity of chemotherapeutic agents, targeted drug delivery is the most promising one.

Areas covered: Liposomes, micelles, albumin-based, polymeric, dendritic and lipid core nanoparticles have been used as carriers to concentrate anticancer drugs in neoplastic tissues, and clinical studies of those preparations are reviewed. In most clinical studies, drug delivery systems reduced drug toxicity. Lipid core nanoparticles (LDE) that bind to cell lipoprotein receptors have the ability to concentrate in neoplastic tissues and were the first artificial non-liposomal system shown in in vivo studies to possess targeting properties. The toxicity reduction achieved by LDE as vehicle of carmustine, etoposide and paclitaxel was singularly strong.

Expert opinion: The reduced toxicity offered by drug delivery systems has expanded treatment population that may benefit from chemotherapy including feeble, overtreated and elderly patients that would otherwise be offered palliative therapy. Drug delivery systems may either prolong the duration of treatments or allow increases in drug dose.

KEYWORDS:

• Cancer treatment
• chemotherapy toxicity
• drug targeting
• LDL receptors and cancer
• lipid core particles
• liposomes
• nanoemulsions
• polymeric nanoparticles

Article highlights

• As confirmed in studies performed in cancer patients, toxicity of chemotherapeutic agents is reduced by association to liposomes and other non-liposomal systems such as polymeric or lipids nanoparticles.

• When associated to carmustine, paclitaxel or etoposide, lipid core nanoparticles that bind to lipoprotein receptors had the ability to strongly reduce the toxicity of those drugs in cancer patients.

• The potential of the existing drug delivery systems should be more intensively explored, mainly to perform chemotherapy in feeble, multi-treated or very aged patients to whom chemotherapy is restricted.

• This potential should be also explored in palliative treatments and to prolong chemotherapy periods or increasing the dose taking advantage of lower toxicity.

• The use of drug delivery systems by the health systems should be intensified taking into account their benefits and potential to decrease costs by diminishing drug toxicity treatments.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

RC Maranhão is recipient of a 1A Research Award from the National Council for Scientific and Technological Development (CNPq, Brasília, Brazil). Our studies on drug delivery were supported by the Foundation for Research Support of the State of São Paulo (FAPESP, São Paulo, Brazil), by the Financier of Studies and Projects (FINEP, Rio de Janeiro, Brazil) and by CNPq.