Turning a water and oil insoluble cisplatin derivative into a nanoparticle formulation for cancer therapy

Abstract

The formulation of water insoluble organic compounds into nanoparticles has become a widely established method for enhancing the delivery and efficacy of cancer therapeutics. Therefore, a comparable approach when applied to water insoluble inorganic compounds should also promote similar advantages. Herein, we have successfully formulated insoluble iodinated cisplatin (CDDP-I) into a LPI NPs (lipid-coated iodinated CDDP nanoparticles). Two separate microemulsions were combined, each containing a precursor for the synthesis of CDDP-I. The resulting CDDP-I precipitate was then coated with an anionic lipid and dispersed in water with the help of an additional lipid. This method allows us to effectively encapsulate CDDP-I and was able to achieve a considerable drug loading of 82 wt%. Administered LPI NPs demonstrated high level accumulation in tumor tissues and exhibited an anti-cancer activity comparable to free CDDP in two melanoma xenograft models without inducing nephrotoxocity. The benefits offered through this delivery formulation are not unique to CDDP-I, as this versatile platform may be extended to the formulation of other inorganic compounds that are both water and oil insoluble into nanoparticles for superior anticancer efficacy.

Lipid-Coated Cisplatin Nanoparticles Induce Neighboring Effect and Exhibit Enhanced Anticancer Efficacy

“…26 Briefly, 200 mM cis-[Pt(NH 3 ) 2 (H 2 O) 2 ](NO 3 ) 2 and 800 mM KCl in water were separately dispersed in a solution composed of Cyclohexane/Igepal CO-520 (71:29, V:V) and Cyclohexane/Triton-X100/Hexanol (75:15:10, V:V:V) (3:1) to form a well-dispersed, water-in-oil reverse micro-emulsion. One hundred μL DOPA (20 mM) was added to the CDDP precursor phase and the mixture was stirred.…”

Curcumin-guided nanotherapy: a lipid-based nanomedicine for targeted drug delivery in breast cancer therapy

“…This could be explained by the active targeting ability of FA which could cell internalization through specific FRs on the surface of MCF-7 cells (Wu et al, 2014). The results also indicated that the enhanced permeability and retention (EPR) effect could appeared effect in highly fenestrated tumor endothelial cells, uptake of NLCs by MCF-7 cells might be enhanced by across the cell membrane via endocytosis or direct penetration may enhance intracellular drug accumulation (Guo et al, 2014).…”

Lipid-based nanocarriers for breast cancer treatment – comprehensive review

“…This was attributed due to the active targeting potential of folic acid, which can internalize through specific folate receptors present on the surface of MCF-7 cells. Enhanced cellular uptake of NLCs by MCF-7 cells may be attributed though the cell membrane via endocytosis or direct penetration may enhance intracellular drug accumulation (Guo et al, 2014). Liu et al (2015) have actively targeted breast tumors using Hyaluronic acid for delivery of Baicalein and Doxorubicin.…”