Nanomedicine Reformulation of Chloroquine and Hydroxychloroquine

Abstract

The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented.

Combination Chemotherapy with Cisplatin and Chloroquine: Effect of Encapsulation in Micelles Formed by Self-Assembling Hybrid Dendritic–Linear–Dendritic Block Copolymers

“…These nanostructures protect the drugs from degradation and can assist in overcoming or avoiding chemoresistance while minimizing systemic toxicity. CDDP [66][67][68] and CQ [47,48,69] have already been successfully formulated into different types of nanocarriers.…”

Electrochemical sensor based on a ZnO-doped graphitized carbon for the electrocatalytic detection of the antibiotic hydroxychloroquine. Application: tap water and human urine

“…It is urgent and necessary to develop a quick, accurate, and user-friendly analytical technique to detect and quantify hydroxychloroquine in pharmaceutical and biological samples. The only difference between the structure of hydroxychloroquine (HCQ) and chloroquine (CQ) is the presence of hydoxd OH groups in the side chain of hydroxychloroquine [ 17 – 19 ]. For hydroxychloroquine detection, a number of methods have been explored [ 20 ], including liquid chromatography-tandem mass spectrometry method [ 21 ], spectrophotometry [ 22 ], liquid-phase micro-extraction [ 23 , 24 ],high-performance liquid chromatography [ 25 , 26 ] and spectrophotometric [ 27 , 28 ] .…”

Pulmonary Delivery of Hydroxychloroquine Nanostructured Lipid Carrier as a Potential Treatment of COVID-19

“…Several nanoformulations were described, including liposomes, polymeric micelles, polymeric nanoparticles, dendrimers, niosome gel, and titanium dioxide nanoparticles. The efficacies of some of these formulations were tested in a tumor model [16]. Therefore, there is a knowledge gap in the use of HCQ-NLCs in the management of acute lung injury.…”