Nanotechnology Based Approaches to Enhance Therapeutic Efficacy of Chloroquine and Hydroxychloroquine– A Review

Background: Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used in the treatment of endemic diseases such as malaria and autoimmune conditions like rheumatoid arthritis. Their anti-apoptotic activity, cost-effectiveness, and convenient oral administration make them effective treatments, either as standalone therapies or in combination with other drugs. However, their use is limited by a narrow therapeutic window, which can lead to potential complications due to organ accumulation and non-specific actions in healthy cells. This risk necessitates exploration into safer clinical applications using nanotechnology. Aim: This scoping review aims to comprehensively assess and analyze the application of nanotechnology to enhance the therapeutic efficacy and safety of CQ and HCQ. Methods: A meticulous search for original studies on nanoparticle formulations of “chloroquine” and “hydroxychloroquine” was conducted. Two reviewers screened titles and abstracts, followed by a detailed assessment of the full articles. Inclusion criteria encompassed original studies in English, Spanish, or Portuguese, focusing on in vitro, in vivo, and ex vivo evaluations. Results: After an exhaustive search across selected databases, 30 articles were meticulously chosen for comprehensive evaluation. The most common properties found for nanoparticles included sizes ranging from 100 to 300 nm, a zeta potential lower than -10, with dendritic derivatives being the most encountered types. Materials used in both production and coating varied, influencing the release and specificity of the nanocarrier. Among therapeutic activities, antimalarial and antitumor activities were the most studied. Conclusion: Studies have demonstrated distinct characteristics acquired by these drugs after encapsulation in various nanoparticles, including reduced toxicity, increased specificity, prolonged systemic circulation, absence of toxic peaks, and potential for different therapeutic approaches.