Interactions of primaquine and chloroquine with PEGylated\ufeff phosphatidylcholine liposomes

Andang Miatmoko,Nuril Fadilatul Nehru,Retno Sari,Ira Nurjannah,Noorma Rosita,Juni Ekowati,Esti Hendradi

doi:10.1038/s41598-021-91866-0

Abstract

This study aimed to analyze the interaction of primaquine (PQ), chloroquine (CQ), and liposomes to support the design of optimal liposomal delivery for hepatic stage malaria infectious disease. The liposomes were composed of hydrogenated soybean phosphatidylcholine, cholesterol, and distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethyleneglycol]-2000), prepared by thin film method, then evaluated for physicochemical and spectrospic characteristics. The calcein release was further evaluated to determine the effect of drug co-loading on liposomal membrane integrity. The results showed that loading PQ and CQ into liposomes produced changes in the infrared spectra of the diester phosphate and carbonyl ester located in the polar part of the phospholipid, in addition to the alkyl group (CH2) in the nonpolar portion. Moreover, the thermogram revealed the loss of the endothermic peak of liposomes dually loaded with PQ and CQ at 186.6 °C, which is identical to that of the phospholipid. However, no crystallinity changes were detected through powder X-ray diffraction analysis. Moreover, PQ, with either single or dual loading, produced the higher calcein release profiles from the liposomes than that of CQ. The dual loading of PQ and CQ tends to interact with the polar head group of the phosphatidylcholine bilayer membrane resulted in an increase in water permeability of the liposomes.

Highlights

This study aimed to analyze the interaction of primaquine (PQ), chloroquine (CQ), and liposomes to support the design of optimal liposomal delivery for hepatic stage malaria infectious disease
This study aimed to provide information related to the effect of PQ and CQ co-loading on the integrity of the bilayer membrane of liposomes
The liposomes were analyzed to determine their physicochemical characteristics and assess their calcein release profiles to confirm the integrity of the liposomal membrane

Summary

Introduction

This study aimed to analyze the interaction of primaquine (PQ), chloroquine (CQ), and liposomes to support the design of optimal liposomal delivery for hepatic stage malaria infectious disease. It was reported that CQ induces the opposite effect via its interaction with the polar part of dipalmitoylphosphatidylcholine (DPPC), causing the absorption of CQ molecules on the surface of the liposomes[15,16,17] This inhibits the movement of the acyl chain, enhancing the rigidity of the bilayer membrane[16]. Condition known to affect the therapeutic index[18,19,21] In this case, membrane rigidity is influenced by the characteristics of the lipid composition employed, as well as the addition of cholesterol to the exterior of the liposomal membrane[21,22]. Optimal delivery to hepatocytes should constitute the main objective when treating a malarial sporozoite invasion Both positive therapeutic effects and reduced hemolysis in cases of patients suffering from glucose-6-phosphate dehydrogenase deficiency should be produced. The use of liposomes as drug carriers is indispensable, rendering an effective strategy for further liposome formulation essential in order to achieve high and stable drug encapsulation

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Conclusion