Effective-Loading of Platinum–Chloroquine into PEGylated Neutral and Cationic Liposomes as a Drug Delivery System for Resistant Malaria Parasites

Abstract

The trans platinum-chloroquine diphosphate dichloride (PtCQ) is a new type of antimalarial drug used to fight parasites resistant to traditional drugs. PtCQ is synthesized by mixing platinum and chloroquine diphosphate (CQ). This study examines two efficient methods for forming a nanodrug, PtCQ-loaded liposomes, for use as a potential antimalarial drug-delivery system: the thin drug-lipid film method to incorporate the drug into a liposomal membrane, and a remote-loading method to load the drug into the interior of a cationic liposome. The membranes accordingly comprised PEGylated neutral or cationic liposomes. PtCQ was efficiently loaded into PEGylated neutral and cationic liposomes using the thin drug-lipid film method (encapsulation efficiency, EE: 76.1 6.7% for neutral liposomes, 1 : 14 drug-to-lipid weight ratio; 70.4 9.8% for cationic liposomes, 1 : 14 drug-to-lipid weight ratio). More PtCQ was loaded into PEGylated neutral liposomes using the remote-loading method than by the thin drug-lipid film method and the EE was maximum (96.1 4.5% for neutral liposomes, 1 : 7 (w/w)). PtCQ was encapsulated in PEGylated cationic liposomes comprising various amounts of cationic lipids (0-20 mol%; EE: 96.9-92.3%) using the remote-loading method. PEGylated neutral liposomes and cationic liposomes exhibited minimum leakage of PtCQ after two months' storage at 4°C, and further exhibited little release under in vitro culture conditions at 37°C for 72 h. These results provide a useful framework for the design of future liposome-based in vivo drug delivery systems targeting the malaria parasite.

The multifaceted role of autophagy in cancer and the microenvironment

“…Such formulations can be further optimized by using antibody‐conjugated and tumor‐targeted liposomes . Of note, CQ liposomes have already been generated in the context of CQ as a malaria drug and were also suitable to simultaneously deliver CQ and a tumoricidal drug . The codelivery of CQ and doxorubicin improved the anticancer activity compared with liposomal doxorubicin .…”

AlPcS₄-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic^® F127 nanomicellar drug carriers

“…Furthermore, PEG-incorporated Clip can prolong drug circulation time to promote passive tumor targeting ability and increase drug delivery efficiency. 48,49 Little information is available regarding the use of Clip for photosensitizer delivery; however, Clip may be another promising AlPcS 4 delivery vector to improve anticancer effect on gastric cancer by increasing AlPcS 4 delivery efficiency, reducing AlPcS 4 binding affinity to HSA, and enhancing AlpcS 4 intracellular uptake.…”

The Multirole of Liposomes in Therapy and Prevention of Infectious Diseases

“…Monensin entrapped in such liposome formulations was tested both in in vitro systems of Plasmodium falciparum cultures and in in vivo murine models of Plasmodium berghei infection and found to be more effective than free monensin given at comparable doses ( 54 ). The trans platinum–chloroquine diphosphate dichloride was recently successfully tested after its encapsulation into PEGylated neutral and cationic liposomes to fight parasites resistant to traditional drugs and proposed as a new therapeutic tool against malaria ( 55 ). Preliminary assays conducted in 1987 using passively loaded chloroquine into RBC-targeted immunoliposomes resulted in significant P. berghei growth inhibition in mice, when compared with administration of the free compound ( 56 ).…”