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<p>The present study aimed to develop and comprehensively evaluate a lipid-based Posaconazole formulation designed to improve pharmacokinetic performance, antifungal efficacy, and biological safety. A cholesterol–soy lecithin (1:2) system was selected as the delivery platform, and formulation parameters were systematically optimised to achieve high entrapment efficiency and nanoscale size. The optimised batch, containing 150 mg lipid and 5 mg drug, demonstrated high entrapment efficiency and nanoscale particle size, confirming excellent agreement between model predictions and experimental outcomes. Pharmacokinetic evaluation revealed significantly greater systemic exposure than with the pure API. The optimised formulation achieved a Cmax of 2.88 µg/mL (2.31 µg/mL API). Plasma concentrations at 12 hours remained higher for the formulation, demonstrating prolonged circulation and improved bioavailability. Drug levels were consistently elevated across all time points. Antifungal activity studies indicated that the liposomal formulation exhibited superior efficacy against <i>Mucor</i> species, with enhanced fungal growth inhibition and greater reduction in fungal burden compared to the free drug. The improved antifungal performance is attributed to sustained drug release, prolonged systemic availability, and improved tissue distribution. Safety assessments confirmed that the formulation was well tolerated. Liver enzyme levels (SGOT: 109.5 IU/L; SGPT: 120.42 IU/L) and haematological parameters (WBC, RBC, haemoglobin, platelets) remained within normal physiological limits and comparable to controls. Kidney toxicity markers, including bilirubin, protein, leukocytes, and specific gravity, showed no evidence of renal impairment. LD₅₀ and maximum tolerated dose evaluations revealed no mortality up to 1000 mg/kg (i.p.) and no abnormal cage-side observations at 500 mg/kg for seven days. In conclusion, the optimised Posaconazole-loaded lipid formulation demonstrated high entrapment efficiency, favourable nanoscale characteristics, significantly enhanced pharmacokinetics, superior antifungal activity, and excellent biological safety. These attributes position the formulation as a promising therapeutic platform for improved antifungal therapy and supportive care applications. </p>

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Optimised Posaconazole-Loaded Liposomes for Enhanced Pharmacokinetics and Antifungal Efficacy in Mucormycosis

  • 期刊论文

  • 发表日期：

    2026年4月14日

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  • Suryadev Sharma,
  • Sanjar Alam,
  • Dheeraj Nagpal

摘要

The present study aimed to develop and comprehensively evaluate a lipid-based Posaconazole formulation designed to improve pharmacokinetic performance, antifungal efficacy, and biological safety. A cholesterol–soy lecithin (1:2) system was selected as the delivery platform, and formulation parameters were systematically optimised to achieve high entrapment efficiency and nanoscale size. The optimised batch, containing 150 mg lipid and 5 mg drug, demonstrated high entrapment efficiency and nanoscale particle size, confirming excellent agreement between model predictions and experimental outcomes. Pharmacokinetic evaluation revealed significantly greater systemic exposure than with the pure API. The optimised formulation achieved a Cmax of 2.88 µg/mL (2.31 µg/mL API). Plasma concentrations at 12 hours remained higher for the formulation, demonstrating prolonged circulation and improved bioavailability. Drug levels were consistently elevated across all time points. Antifungal activity studies indicated that the liposomal formulation exhibited superior efficacy against Mucor species, with enhanced fungal growth inhibition and greater reduction in fungal burden compared to the free drug. The improved antifungal performance is attributed to sustained drug release, prolonged systemic availability, and improved tissue distribution. Safety assessments confirmed that the formulation was well tolerated. Liver enzyme levels (SGOT: 109.5 IU/L; SGPT: 120.42 IU/L) and haematological parameters (WBC, RBC, haemoglobin, platelets) remained within normal physiological limits and comparable to controls. Kidney toxicity markers, including bilirubin, protein, leukocytes, and specific gravity, showed no evidence of renal impairment. LD₅₀ and maximum tolerated dose evaluations revealed no mortality up to 1000 mg/kg (i.p.) and no abnormal cage-side observations at 500 mg/kg for seven days. In conclusion, the optimised Posaconazole-loaded lipid formulation demonstrated high entrapment efficiency, favourable nanoscale characteristics, significantly enhanced pharmacokinetics, superior antifungal activity, and excellent biological safety. These attributes position the formulation as a promising therapeutic platform for improved antifungal therapy and supportive care applications.