Lipid-based nanoparticulate systems for the delivery of anti-cancer drug cocktails: Implications on pharmacokinetics and drug toxicities.
The use of drug cocktails has become a widely adopted strategy in clinical cancer therapy. Cytotoxic drug cocktails are often administered based on maximum tolerated dose (MTD) of each agent, with the belief of achieving maximum cell kill through tolerable toxicity level. Yet, MTD administration may not have fully captured the therapeutic synergism that exists among the individual agents in the drug cocktail, as the response to a cocktail regimen, that is, whether the effect is synergistic or not, could be highly sensitive to the concentration ratios of the individual drugs at the site of action. It is important to realize that the inherently different pharmacokinetic profiles of the individual agents could have significant influence on the response to an anti-cancer drug cocktail by dictating the amount of the individual agents reaching the tumor site and therefore the concentration ratios. Furthermore, the individual agents may have unfavorable pharmacokinetic interactions that add to the difficulty in determining the therapeutic and/or toxicological effects of the drug cocktail. In this review, we will focus on how lipid-based nanoparticulate systems could address the above issues associated with anti-cancer drug cocktails. Specifically, we will highlight the use of liposome systems as the means to control and coordinate the delivery of various anti-cancer drug cocktails, encompassing conventional chemotherapeutics, chemosensitizing agents and molecularly targeted agents.
Chiu
Gigi N C
GN
Department of Pharmacy, National University of Singapore, Singapore. phacncg@nus.edu.sg
Wong
Man-Yi
MY
Ling
Leong-Uung
LU
Shaikh
Ishaque M
IM
Tan
Kuan-Boone
KB
Chaudhury
Anumita
A
Tan
Bee-Jen
BJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015507:Drugs, Investigational / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000627:therapeutic use*; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*
D004337:Drug Carriers; D015507:Drugs, Investigational; D008081:Liposomes