Drug Delivery Devices and Targeting Agents for Platinum(II) Anticancer Complexes

Abstract

An ideal platinum-based delivery device would be one that selectively targets cancerous cells, can be systemically delivered, and is non-toxic to normal cells. It would be beneficial to provide drug delivery devices for platinum-based anticancer agents that exhibit high drug transport capacity, good water solubility, stability during storage, reduced toxicity, and enhanced anticancer activity in vivo. However, the challenges for developing drug delivery devices include carrier stability in vivo, the method by which extracellular or intracellular drug release is achieved, overcoming the various mechanisms of cell resistance to drugs, controlled drug release to cancer cells, and platinum drug bioavailability. There are many potential candidates under investigation including cucurbit[n]urils, cyclodextrins, calix[n]arenes, and dendrimers, with the most promising being those that are synthetically adaptable enough to attach to targeting agents.

Targeting and delivery of platinum-based anticancer drugs

“…Cucurbit[n]urils (n = 6, 7, 8) have become the most attractive macrocycles used for encapsulating platinum anticancer drugs in recent years. 95 Such systems have shown particular potential as protective carriers in drug delivery. Cucurbit[n]urils contain two symmetrical hydrophilic carbonyl lined portals, capping a central hydrophobic cavity, thus imparting an amphipathic nature to the macrocycles (Fig.…”

Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin

“…Copolymer- [7] or liposomalbased [8,9] carriers have been used to improve the delivery of platinum drugs for the enhanced permeability and retention (EPR) effect of macromolecules on tumors, but altered tissue distribution would lead to new toxicity profiles in clinical trials [10]. Recently, molecular containers with large cavities such as cucurbituril series were examined as drug delivery vehicles for platinum complexes [11], but poor water solubility and inefficient transport limit their potential application [12]. As an alternative, ligand-receptor-mediated delivery systems have attracted much attention because of their non-immunogenic and site-specific targeting potential to the ligand-specific bio-sites [13].…”

Amino acid-modified PAMAM dendritic nanocarriers as effective chemotherapeutic drug vehicles in cancer treatment: a study using zebrafish as a cancer model

“…Generally, the primary critical consideration for biomaterials is cytotoxicity; PAMAM dendrimers have demonstrated biocompatibility with animal physiology. 43,44 The high survival rate of HeLa cells aer 24 h exposure to the dendrimer G4.5 and both dendrimer derivatives (GH and GHC) conrmed their compatibility and suitability for drug delivery (Fig. 4A).…”