In vitro release, ex vivo penetration, and in vivo dermatokinetics of ketoconazole-loaded solid lipid nanoparticles for topical delivery View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-01-07

AUTHORS

Mohhammad Ramzan, Samuel Gourion-Arsiquaud, Afzal Hussain, Jaspreet Singh Gulati, Qihong Zhang, Sonia Trehan, Vinam Puri, Bozena Michniak-Kohn, Indu Pal Kaur

ABSTRACT

The study focused to evaluate and investigate optimized (using QbD) and novel ketoconazole (KTZ)-loaded solid lipid nanoparticles (KTZ-SLNs; 2% w/v KTZ) for enhanced permeation across skin. KTZ-SLNs were evaluated for size, distribution, zeta potential (ZP), percent entrapment efficiency (%EE), drug release, morphology (HRTEM and FESEM), thermal behaviour (DSC), spectroscopic (FTIR), and solid-state/diffraction characterization (X-ray diffraction, XRD). Moreover, ex vivo permeation and drug deposition into rat skin were conducted using Franz diffusion cell. The same was confirmed using human dermatome skin and fluorescence, confocal Raman, and vibrational ATR-FTIR microscopic methods. An in vivo dermatokinetics study was performed in rats to assess the extent of KTZ permeation into the skin. Stability including accelerated and photostability studies were conducted at different temperatures (2–8, 30, and 40 °C) for 12 months. The spherical, optimized KTZ-SLN formulation (KOF1) showed particle size of 293 nm and high EE of 88.5%. Results of FTIR, DSC, and XRD confirmed formation of KTZ-SLNs and their amorphous nature due to presence of KTZ in a dissolved state in the lipid matrix. In vitro release was slow and sustained whereas ex vivo permeation parameters were significantly high in KTZ-SLNs as compared to free drug suspension (KTZ-SUS) and marketed product (Nizral®; 2% KTZ w/v). Drug retention was 10- and five-fold higher than KTZ-SUS and marketed product, respectively. In vivo dermatokinetics parameters improved significantly with SLN formulation (410–900% enhanced). Confocal Raman spectroscopy experiment showed that KTZ-SLNs could penetrate beyond the human stratum corneum into viable epidermis. Fluorescent microscopy also indicated improved penetration of KTZ-SLNs. KTZ-SLNs were photostable and showed long-term stability over 12 months under set conditions.Graphical abstract More... »

PAGES

1659-1683

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13346-021-01058-6

DOI

http://dx.doi.org/10.1007/s13346-021-01058-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1144475521

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34993923


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103 results
104 results of FTIR
105 retention
106 size
107 skin
108 solid lipid nanoparticles
109 spectroscopic
110 spectroscopy experiments
111 stability
112 state
113 stratum corneum
114 study
115 suspension
116 temperature
117 thermal behavior
118 topical delivery
119 viable epidermis
120 vivo penetration
121 vivo permeation
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