Nanocarriers for delivery of platinum anticancer drugs

Abstract

Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

“…Other examples include liposomal formulations of platinum drugs (Oberoi et al, 2013), such as: 1) Lipoplatin (Regulon Inc., Mountain View, CA), a liposomal cisplatin formulation, that has received orphan drug status from the EMA for the treatment of pancreatic adenocarcinoma and is also being investigated in phase II/III clinical trials for different cancer-types (Boulikas, 760 2009); 2) Lipoxal (Regulon Inc., Mountain View, CA), a liposomal formulation of oxaliplatin (Fig. 1), that has been under investigation for advanced gastrointestinal cancer in a phase I clinical trial (Stathopoulos et al, 2006); and 3) MBP-426 (Mebiopharm Co. Ltd, Tokyo, Japan), a transferrin conjugated liposomal formulation of oxaliplatin, currently undergoing a phase II clinical trial for solid tumors (for more information on liposomal formulation of platinum drugs see Oberoi et al, 2013).…”

“…As liposomal drug delivery systems have proven to be quite effective at enhancing the efficacy and safety of chemotherapeutic agents for cancer treatment, many novel liposomal formulations are currently being investigated, some of which have already entered late stage clinical trials (Slingerland et al, 2012;May and Li, 2013;Oberoi et al, 2013;Wicki et al, 2015). The most recent example is ThermoDox, a temperaturesensitive liposomal formulation of DOX, which is currently being investigated in a phase III clinical trial for hepatocellular carcinoma and a phase II clinical trial for breast cancer and colorectal liver metastases (May and Li, 2013).…”

“…1), that has been under investigation for advanced gastrointestinal cancer in a phase I clinical trial (Stathopoulos et al, 2006); and 3) MBP-426 (Mebiopharm Co. Ltd, Tokyo, Japan), a transferrin conjugated liposomal formulation of oxaliplatin, currently undergoing a phase II clinical trial for solid tumors (for more information on liposomal formulation of platinum drugs see Oberoi et al, 2013). Tables 2-4 provide information regarding liposomal drug formulation, in terms of product name, drug, liposome-type, indications, lipid compositions, particle size, and status in phase I (Table 2), phase II (Table 3), and phase III (Table 4) clinical trials.…”

trans-Platinum(ii) complex of 3-aminoflavone – synthesis, X-ray crystal structure and biological activities in vitro

“…[3][4][5] The mechanisms underlying resistance to cisplatin may be connected with reduced intracellular accumulation due to reduced drug uptake enhanced efflux, conjugation with intracellular thiols (metallothionein, glutathione), enhanced repair of platinum DNA adducts or changes in molecular pathways involved in regulation of cell survival/cell death. 6,7 Based on the limitations in the use of the platinum drugs, novel anticancer metal compounds have been designed with the aim of reducing sideeffects or synthesizing drugs with less propensity to induce drug resistance.…”

Design of a novel theranostic nanomedicine: synthesis and physicochemical properties of a biocompatible polyphosphazene–platinum(II) conjugate

“…7,12 In particular, extensive research has been focused in recent years on the development of polymeric conjugate drugs by incorporating the antitumor-active moiety of OX in many different kinds of polymers. In the early stage, the active moiety (dach)Pt(II) was conjugated simply to the poly(ethylene glycols) (PEG) using a peptide spacer 13 or to the hydrophilic N-(2-hydroxypropyl) methacrylamide using a peptide-aminomalonate spacer (AP5346), which is still in clinical Phase II trials.…”