Preliminary studies on drug delivery of polymeric primaquine microparticles using the liver high uptake effect based on size of particles to improve malaria treatment

Silva, Aline Oliveira da; Portilho, Filipe Leal; Matos, Ana Paula dos Santos; Ricci-Júnior, Eduardo; Alencar, Luciana Magalhães Rebêlo; Santos, Clenilton Costa dos; Paumgartten, Francisco José Roma; Iram, Surtaj H.; Mazier, Dominique; Franetich, Jean‐François; Alexis, Frank; Santos-Oliveira, Ralph

doi:10.1016/j.msec.2021.112275

Cited by 13 publications

(8 citation statements)

References 37 publications

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“…On the other hand, the more than 2-fold lower AUC and concentration of primaquine nanoparticles in plasma will certainly reduce unwanted adverse effects related to high plasma concentrations. Hence, we can conclude that chitosan nanoencapsulation widens the therapeutic window of primaquine by a factor of more than 6, matching the 6.5 times increased volume of distribution in favor of its target organ [16], [31].…”

Section: Discussionmentioning

confidence: 99%

Primaquine-chitosan Nanoparticle Improves Drug Delivery to Liver Tissue in Rats

Rinaldi

Hawa

Purwantyastuti

et al. 2022

Open Access Maced J Med Sci

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Introduction: Primaquine is one of the essential medicines used to treat malaria due to Plasmodium vivax. Primaquine acts by eradicating hypnozoites in the liver, and its effect is dependent on the drug concentrations in the target tissue. The present study aimed to prepare primaquine in nanoparticle formulation using chitosan as carriers and improve on-target primaquine delivery to the liver. Methods: Primaquine-loaded chitosan nanoparticles were prepared using the ionic gelation method variations. Then, the resulting primaquine-chitosan nanoparticles were administered to the rats and compared with conventional primaquine. Afterward, plasma and liver concentrations of primaquine were quantified. Results: The primaquine-chitosan nanoparticles obtained were at 47.9 nm. The area under the curve for primaquine-chitosan nanoparticles resulted lower in the area under the curve (AUC) and Cmax, 0.46 and 0.42 times of conventional primaquine, respectively. However, no differences were found in time to reach Cmax (Tmax). Primaquine liver concentrations obtained with primaquine-chitosan nanoprimaquine resulted in 3 times higher than primaquine concentration. Conclusion: Enhanced drug delivery to rat liver tissue by primaquine-chitosan nanoparticles may improve on-target drug delivery to the liver, enhance primaquine ant hypnozoites effects, and reduce unwanted side effects in the circulation.

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Section: Discussionmentioning

confidence: 99%

Primaquine-chitosan Nanoparticle Improves Drug Delivery to Liver Tissue in Rats

Rinaldi

Hawa

Purwantyastuti

et al. 2022

Open Access Maced J Med Sci

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“…The causative parasite has developed mechanisms of resistance to treatments employed over the years, and the currently available options have many adverse effects and need various daily administrations to achieve the therapeutic effect, which further worsens adverse effects [ 41 ]. Aiming to improve treatment proposals, da Silva de Barros et al [ 42 ] encapsulated primaquine in polylactic acid (PLA) polymeric microparticles to fight the hepatic primary phase of the parasite. In vitro release studies showed a prolonged release of the drug, which allowed to reduce the number of administrations and adverse effects, while in vivo studies demonstrated long drug permanence in hepatocytes (74.55%).…”

Section: Polymeric Microparticles In Biological Testsmentioning

confidence: 99%

Microparticles in the Development and Improvement of Pharmaceutical Formulations: An Analysis of In Vitro and In Vivo Studies

Silva

Menezes

Oliveira

et al. 2023

IJMS

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Microparticulate systems such as microparticles, microspheres, microcapsules or any particle in a micrometer scale (usually of 1–1000 µm) are widely used as drug delivery systems, because they offer higher therapeutic and diagnostic performance compared to conventional drug delivery forms. These systems can be manufactured with many raw materials, especially polymers, most of which have been effective in improving the physicochemical properties and biological activities of active compounds. This review will focus on the in vivo and in vitro application in the last decade (2012 to 2022) of different active pharmaceutical ingredients microencapsulated in polymeric or lipid matrices, the main formulation factors (excipients and techniques) and mostly their biological activities, with the aim of introducing and discussing the potential applicability of microparticulate systems in the pharmaceutical field.

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“…Furthermore, primaquine polymeric microparticles (PPM) in in vivo experiments using a murine model showed partial efficacy and protection against parasite Frontiers in Pharmacology frontiersin.org development compared with that of free primaquine, suggesting the potential of this drug delivery system for the treatment of malaria (da Silva de Barros et al, 2021). Three drug carriers based on lipid formulations loaded with primaquine, solid lipid nanoparticles, nanoemulsions and nanostructured lipid carriers were developed and evaluated; all lipid formulations could successfully protect erythrocytes from cell lysis caused by free primaquine (Wu et al, 2021).…”

Section: Recent Studies On Nanotechnology In Malaria Treatmentmentioning

confidence: 99%

“…Side effects frequently related to conventional antimalarial drugs include abdominal pain and gastrointestinal symptoms such as vomiting, jaundice, itching, hypoglycemia, anemia, dizziness, coma, and altered consciousness ( Novitt-Moreno et al, 2021 ; Rashidzadeh et al, 2021 ). In addition, during prolonged use, there is a risk of hemolysis (tafenoquine and primaquine), retinopathy, mental confusion, cardiac complications (tafenoquine and chloroquine) ( Novitt-Moreno et al, 2021 ), and gastric irritation (primaquine) ( da Silva de Barros et al, 2021 ). Skin hypersensitivity reactions to sulfadoxine-pyrimethamine (Stevens-Johnson syndrome), severe hepatoxicity, and neuropsychiatric reactions to mefloquine have also been reported ( Frey et al, 2010 ; Ashley and Phyo, 2018 ).…”

Section: Resistance To Antimalarialsmentioning

confidence: 99%

Potential of nanoformulations in malaria treatment

Chaves

Moraes²,

Ferrarini³

et al. 2022

Front. Pharmacol.

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Malaria is caused by the protozoan Plasmodium sp and affects millions of people worldwide. Its clinical form ranges from asymptomatic to potentially fatal and severe. Current treatments include single drugs such as chloroquine, lumefantrine, primaquine, or in combination with artemisinin or its derivatives. Resistance to antimalarial drugs has increased; therefore, there is an urgent need to diversify therapeutic approaches. The disease cycle is influenced by biological, social, and anthropological factors. This longevity and complexity contributes to the records of drug resistance, where further studies and proposals for new therapeutic formulations are needed for successful treatment of malaria. Nanotechnology is promising for drug development. Preclinical formulations with antimalarial agents have shown positive results, but only a few have progressed to clinical phase. Therefore, studies focusing on the development and evaluation of antimalarial formulations should be encouraged because of their enormous therapeutic potential.

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Preliminary studies on drug delivery of polymeric primaquine microparticles using the liver high uptake effect based on size of particles to improve malaria treatment

Cited by 13 publications

References 37 publications

Primaquine-chitosan Nanoparticle Improves Drug Delivery to Liver Tissue in Rats

Primaquine-chitosan Nanoparticle Improves Drug Delivery to Liver Tissue in Rats

Microparticles in the Development and Improvement of Pharmaceutical Formulations: An Analysis of In Vitro and In Vivo Studies

Potential of nanoformulations in malaria treatment

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