The Targeted-liposome Delivery System of Antitumor Drugs.

The liposome delivery system has been intensively explored as novel drug delivery system (DDS) for antitumor drugs, due to its safety, selective cytotoxicity, long circulation and slow elimination in blood, which is favorable for cancer therapy. The liposome-based chemotherapeutics are used to treat a variety of cancers to enhance the therapeutic index of antitumor drugs. Here, the author reviewed the important targets for cancer therapy and the pharmacokinetic behavior of liposomal drugs in vivo, as well as the application of the targeting liposomal system in cancer therapy. Considering further application for clinical use, the great challenges of the liposome-based delivery system were also proposed as follows: 1) prepare stealth liposome with steric stabilization and further enhance the therapeutic effects and safety; 2) explore more safe clinical targets and complementary or different types of targeting liposome; 3) thirdly, more investment is needed on the research of pharmacokinetics of the elements such as the ligands (antibody), PEG and lipids of liposome delivery system as well as safety evaluation. Considering the complex process of the liposomal encapsulation drugs in vivo, the author inferred that there are maybe different forms of the encapsulation drug to be internalized by the tumor tissues at the same time and space, although there are little reports on it.

Effects of Drug Transporters on Pharmacological Responses and Safety.

Recently, it is realized that transporters, apart from enzymes, play a key role in drug metabolism and pharmacokinetics. More and more pharmaceutical researchers focused on transporter study and found that drug transporters not only involved in pharmacokinetics including absorption, distribution, metabolism and excretion (ADME). but also in Drug-Drug interactions (DDIs). DDIs induced by drug transporters are the important safety evaluation factors which have to be taken into account at stage of drug discovery and development. Therefore, it should pay more attention to the studies on step of preclinical and clinical trial. In this review, the author focused on the effects of drug transporters on pharmacological and safety responses, such as the effects on plasma elimination half-lives, on drug accumulation in body after repeated dosing, on potentiating either pharmacological or adverse effects and molecular mechanisms of transporter-mediated DDIs. Present studies showed that DDIs involving the drug transporters including ABC transporters, organic anion and cation transporters, peptide transporters, monocarboxylate transporters, nucleoside transporters and folate transporters, and the possible side effects derived from clinical combination therapy must pay attention. The author also discussed the molecular mechanisms of transporter-mediated DDIs by the data obtained from preclinical and clinical studies, and inferred the available curative effects and the potential risk of the drug combination involving these drug transporters, which provides a reference for the safety of clinical medication and a consideration for a successful drug discovery. This article carefully reviewed transporter-based DDIs and highlighted areas that DDIs were poorly predicted through transporters or areas are still confronted with challenges in future.