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<p>Olmesartan medoxomil (OMN), a highly selective antihypertensive agent but, with problematic oral delivery due to its low solubility and limited bioavailability. Therefore, biomimetic lipid-based niosomes were adopted as a novel approach to enhance OMN solubility and boost its transdermal delivery (TD). Initially, conventional niosomes were prepared by thin film hydration method. Formulation parameters were adjusted to obtain entrapment efficiency (EE &gt; 75%), particle size (PS &lt; 300&#xa0;nm), zeta potential (ZP &gt; ± 25 mV), and polydispersity index (PDI &lt; 0.5). Based on these parameters, OMN-Ns-3 was selected for further modulation. Concomitantly, screening studies of OMN in 9 liquid lipids; clove oil, Maisine<sup>®</sup> CC, Transcutol<sup>®</sup> HP, castor oil, olive oil, Miglyol<sup>®</sup> 812, soybean oil, sesame oil, and cottonseed oil were performed. Among them, the first three showed the highest solubility of OMN; ~16.30 ± 1.80, 25.60 ± 2.20, and 38.35 ± 1.30&#xa0;mg/mL, respectively. Hence, they were incorporated into OMN-Ns-3 to obtain the modulated niosomal formulation; M/C-OMN-Ns-T. It showed accepted EE 98.70 ± 1.40%, PS 186.30 ± 2.40&#xa0;nm, ZP -36.20 ± 0.70 mV, and PDI 0.34 ± 0.03. It showed enhanced cumulative amount of OMN permeated; Q<sub>24</sub> 93.72 ± 0.49%, Q<sub>48</sub> 97.56 ± 0.66%, and Q<sub>72</sub> 98.22 ± 1.15%. Ex vivo studies showed significantly enhanced flux (J<sub>max</sub>) compared to conventional niosomes with enhancement ratio values ~ 1.6 at 24/48&#xa0;h, and 1.5 at 72&#xa0;h (<i>p</i> &lt; 0.0001). Confocal Laser Scanning Microscopy showed vast distribution and deep localization of fluorescent M/C-OMN-Ns-T, creating in-skin depot for sustained OMN diffusion to the systemic circulation. TEM images showed nanosized, non-aggregated spherical vesicles. Physical stability studies showed no significant changes in EE, PS, ZP, and PDI. M/C-OMN-Ns-T formulated into transdermal patch (TP) showed accepted physicochemical properties including; thickness, folding endurance, surface pH, drug content Q<sub>24</sub>, and Q<sub>48</sub>. In vivo pharmacokinetic studies of TP showed significantly enhanced relative bioavailability ~ 674.04% compared to angiosartan oral tablets (<i>p</i> &lt; 0.0001). It could be concluded that TD of M/C-OMN-Ns-T reflected its superiority over conventional lipid-free niosomes. Our study introduced the potential of liquid lipids as biomimetic fluidizing agents for enhanced TD of conventional nanocarriers. The developed TP could be a competent alternative to conventional oral delivery of OMN.</p> Graphical abstract <p></p>

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Advanced lipid-based niosomes for enhanced transdermal delivery of olmesartan medoxomil via intracutaneous drug depot: a novel biomimicry approach

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • Shahinaze A. Fouad,
  • Mostafa I. Gebril,
  • Fathy I. Abd Allah,
  • Mahmoud H. Teaima,
  • Mohamed El-Nabarawi,
  • Mohammed Elmowafy,
  • Omnia M. Sarhan

摘要

Olmesartan medoxomil (OMN), a highly selective antihypertensive agent but, with problematic oral delivery due to its low solubility and limited bioavailability. Therefore, biomimetic lipid-based niosomes were adopted as a novel approach to enhance OMN solubility and boost its transdermal delivery (TD). Initially, conventional niosomes were prepared by thin film hydration method. Formulation parameters were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 300 nm), zeta potential (ZP > ± 25 mV), and polydispersity index (PDI < 0.5). Based on these parameters, OMN-Ns-3 was selected for further modulation. Concomitantly, screening studies of OMN in 9 liquid lipids; clove oil, Maisine® CC, Transcutol® HP, castor oil, olive oil, Miglyol® 812, soybean oil, sesame oil, and cottonseed oil were performed. Among them, the first three showed the highest solubility of OMN; ~16.30 ± 1.80, 25.60 ± 2.20, and 38.35 ± 1.30 mg/mL, respectively. Hence, they were incorporated into OMN-Ns-3 to obtain the modulated niosomal formulation; M/C-OMN-Ns-T. It showed accepted EE 98.70 ± 1.40%, PS 186.30 ± 2.40 nm, ZP -36.20 ± 0.70 mV, and PDI 0.34 ± 0.03. It showed enhanced cumulative amount of OMN permeated; Q24 93.72 ± 0.49%, Q48 97.56 ± 0.66%, and Q72 98.22 ± 1.15%. Ex vivo studies showed significantly enhanced flux (Jmax) compared to conventional niosomes with enhancement ratio values ~ 1.6 at 24/48 h, and 1.5 at 72 h (p < 0.0001). Confocal Laser Scanning Microscopy showed vast distribution and deep localization of fluorescent M/C-OMN-Ns-T, creating in-skin depot for sustained OMN diffusion to the systemic circulation. TEM images showed nanosized, non-aggregated spherical vesicles. Physical stability studies showed no significant changes in EE, PS, ZP, and PDI. M/C-OMN-Ns-T formulated into transdermal patch (TP) showed accepted physicochemical properties including; thickness, folding endurance, surface pH, drug content Q24, and Q48. In vivo pharmacokinetic studies of TP showed significantly enhanced relative bioavailability ~ 674.04% compared to angiosartan oral tablets (p < 0.0001). It could be concluded that TD of M/C-OMN-Ns-T reflected its superiority over conventional lipid-free niosomes. Our study introduced the potential of liquid lipids as biomimetic fluidizing agents for enhanced TD of conventional nanocarriers. The developed TP could be a competent alternative to conventional oral delivery of OMN.

Graphical abstract