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<p>Clotrimazole (CMZ), an antimycotic drug, has been reported to be experimentally effective for <i>Plasmodium falciparum</i> malaria treatment. However, clotrimazole is limited by poor dissolution in aqueous medium and degradation in harsh gastrointestinal tract (GIT) environments. Chitosan-coated nanoplatforms protect drugs against GIT degradation and improve their dissolution and therapeutic effects. Thus, in this study, clotrimazole was formulated in solidified reversed micellar solution (SRMS)-based chitosan-coated solid lipid nanoparticles (CS-SLNs) with the aim of protecting it against GIT degradation, enhancing its dissolution, and improving its antimalarial efficacy. Free and drug-loaded neutral and chitosan-coated SLNs were prepared employing high-shear melt-emulsification and thereafter investigated in terms of particle characteristics, encapsulation efficiency, scanning electron microscopy (SEM), powder x-ray diffractometry (PXRD), Fourier transform infra-red (FI-IR) spectroscopy, release profiles in media [hydrochloric acid buffer (pH = 1.2) and phosphate buffer (pH = 6.8)] containing 0.5% Tween 80, stability, and cytotoxicity. Antimalarial, hematological and histopathological studies were carried out in mice. The developed clotrimazole-loaded chitosan-coated SRMS-based SLNs (CMZ-CS-SLNs) were stable and showed good colloidal properties (size 346.35 ± 3.40&#xa0;nm, PDI 0.259 ± 0.06, and ζ-potential + 30.54 ± 1.76&#xa0;mV) and good encapsulation efficiency (79.03%). The release of CMZ from the formulations was unaffected by pH, with CMZ-CS-SLNs showing controlled drug release. PXRD confirmed the molecularly dispersed CMZ in CMZ-CS-SLNs, FT-IR results indicated chemical structure integrity of CMZ and components compatibility, while SEM showed smooth and uniform particles with a layer of polymer coating in CMZ-CS-SLNs. Furthermore, there were minimal effects on hematological parameters and significantly (****<i>P</i> &lt; 0.0001) greater reduction in parasitemia (~ 3x) for CMZ-CS-SLNs (19.80%) than oral CMZ suspension (6.1%). Moreover, CMZ-CS-SLN demonstrated minimal toxicity on Caco-2 cells and equally ameliorated the <i>Plasmodium berghei</i>-induced liver and kidney complications in the malariogenic mice. Thus, SRMS-based CS-SLN is a promising nano-platform for enhanced delivery and antimalarial activity of CMZ.</p>

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Engineering Solidified Reverse Micellar Solution-Based Chitosan-Coated Lipid Nanoparticles for Enhanced Antimalarial Activity of Clotrimazole

  • 期刊论文

  • 发表日期：

    2025年2月12日

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  • Franklin Chimaobi Kenechukwu,
  • Miracle Ikechukwu Ezegwui,
  • Thaddeus Harrison Gugu,
  • God’spower Tochukwu Isaac,
  • Evaristus Chinonso Odo,
  • Godwin Chikamso Chukwu,
  • Chinazom Precious Agbo,
  • Mumuni Audu Momoh,
  • Wilfred Ikechukwu Ugwuoke,
  • Teerapol Srichana,
  • Anthony Amaechi Attama

摘要

Clotrimazole (CMZ), an antimycotic drug, has been reported to be experimentally effective for Plasmodium falciparum malaria treatment. However, clotrimazole is limited by poor dissolution in aqueous medium and degradation in harsh gastrointestinal tract (GIT) environments. Chitosan-coated nanoplatforms protect drugs against GIT degradation and improve their dissolution and therapeutic effects. Thus, in this study, clotrimazole was formulated in solidified reversed micellar solution (SRMS)-based chitosan-coated solid lipid nanoparticles (CS-SLNs) with the aim of protecting it against GIT degradation, enhancing its dissolution, and improving its antimalarial efficacy. Free and drug-loaded neutral and chitosan-coated SLNs were prepared employing high-shear melt-emulsification and thereafter investigated in terms of particle characteristics, encapsulation efficiency, scanning electron microscopy (SEM), powder x-ray diffractometry (PXRD), Fourier transform infra-red (FI-IR) spectroscopy, release profiles in media [hydrochloric acid buffer (pH = 1.2) and phosphate buffer (pH = 6.8)] containing 0.5% Tween 80, stability, and cytotoxicity. Antimalarial, hematological and histopathological studies were carried out in mice. The developed clotrimazole-loaded chitosan-coated SRMS-based SLNs (CMZ-CS-SLNs) were stable and showed good colloidal properties (size 346.35 ± 3.40 nm, PDI 0.259 ± 0.06, and ζ-potential + 30.54 ± 1.76 mV) and good encapsulation efficiency (79.03%). The release of CMZ from the formulations was unaffected by pH, with CMZ-CS-SLNs showing controlled drug release. PXRD confirmed the molecularly dispersed CMZ in CMZ-CS-SLNs, FT-IR results indicated chemical structure integrity of CMZ and components compatibility, while SEM showed smooth and uniform particles with a layer of polymer coating in CMZ-CS-SLNs. Furthermore, there were minimal effects on hematological parameters and significantly (****P < 0.0001) greater reduction in parasitemia (~ 3x) for CMZ-CS-SLNs (19.80%) than oral CMZ suspension (6.1%). Moreover, CMZ-CS-SLN demonstrated minimal toxicity on Caco-2 cells and equally ameliorated the Plasmodium berghei-induced liver and kidney complications in the malariogenic mice. Thus, SRMS-based CS-SLN is a promising nano-platform for enhanced delivery and antimalarial activity of CMZ.