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. 2024 Jan 10:19:209-230.
doi: 10.2147/IJN.S438564. eCollection 2024.

Repaglinide-Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box-Behnken Design, Characterization, and In Vivo Evaluation

Hany S M Ali  1   2 , Nader Namazi  1 , Hossein M Elbadawy  3 , Abdelaziz A A El-Sayed  4   5 , Sameh A Ahmed  6   7 , Rawan Bafail  1 , Mohannad A Almikhlafi  3 , Yaser M Alahmadi  8
Affiliations

Repaglinide-Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box-Behnken Design, Characterization, and In Vivo Evaluation

Hany S M Ali et al. Int J Nanomedicine. .

Abstract

Background: Repaglinide (REP) is an antidiabetic drug with limited oral bioavailability attributable to its low solubility and considerable first-pass hepatic breakdown. This study aimed to develop a biodegradable chitosan-based system loaded with REP-solid lipid nanoparticles (REP-SLNs) for controlled release and bioavailability enhancement via transdermal delivery.

Methods: REP-SLNs were fabricated by ultrasonic hot-melt emulsification. A Box-Behnken design (BBD) was employed to explore and optimize the impacts of processing variables (lipid content, surfactant concentration, and sonication amplitude) on particle size (PS), and entrapment efficiency (EE). The optimized REP-SLN formulation was then incorporated within a chitosan solution to develop a transdermal delivery system (REP-SLN-TDDS) and evaluated for physicochemical properties, drug release, and ex vivo permeation profiles. Pharmacokinetic and pharmacodynamic characteristics were assessed using experimental rats.

Results: The optimized REP-SLNs had a PS of 249±9.8 nm and EE of 78%±2.3%. The developed REP-SLN-TDDS demonstrated acceptable characteristics without significant aggregation of REP-SLNs throughout the casting and drying processes. The REP-SLN-TDDS exhibited a biphasic release pattern, where around 36% of the drug load was released during the first 2 h, then the drug release was sustained at around 80% at 24 h. The computed flux across rat skin for the REP-SLN-TDDS was 2.481±0.22 μg/cm2/h in comparison to 0.696±0.07 μg/cm2/h for the unprocessed REP, with an enhancement ratio of 3.56. The REP-SLN-TDDS was capable of sustaining greater REP plasma levels over a 24 h period (p<0.05). The REP-SLN-TDDS also reduced blood glucose levels compared to unprocessed REP and commercial tablets (p<0.05) in experimental rats.

Conclusion: Our REP-SLN-TDDS can be considered an efficient therapeutic option for REP administration.

Keywords: Box–Behnken design; bioavailability; chitosan; repaglinide; solid-lipid nanoparticles; transdermal.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Size distribution of representative repaglinide–solid lipid nanoparticles (A) and TEM micrograph (B).
Figure 2
Figure 2
Three-dimensional surface diagrams and contour plots showing the impact of lipid content–surfactant concentration (a), lipid content–amplitude, (b) and surfactant concentration–amplitude, (c) on size of solid-lipid nanoparticles.
Figure 3
Figure 3
Three-dimensional surface diagrams and contour plots showing the impact of lipid content–surfactant concentration (a), lipid content–amplitude, (b) and surfactant concentration–amplitude, (c) on entrapment efficiency of solid-lipid nanoparticles.
Figure 4
Figure 4
Contour plots of desirability for the optimized REP-SLNs.
Figure 5
Figure 5
DSC thermograms of repaglinide (A), poloxamer 188 (B), Compritol 888 (C), mannitol (D), and repaglinide-loaded solid-lipid nanoparticles (E).
Figure 6
Figure 6
A chitosan transdermal system loaded with REP-SLNs (A) vs a plain system (B).
Figure 7
Figure 7
Size distribution of redispersed repaglinide solid-lipid nanoparticles from chitosan patches.
Figure 8
Figure 8
Release of repaglinide from tested formulations.
Figure 9
Figure 9
Ex vivo permeation of repaglinide from solid-lipid nanoparticle transdermal system (REP-SLN-TDDS) and unprocessed repaglinide (REP).
Figure 10
Figure 10
Plasma concentration–time profiles of repaglinide after oral and transdermal administration in rats.
Figure 11
Figure 11
Reduction in blood glucose levels following administration of the REP-SLN-TDDS in comparison with commercial REP tablets in diabetic rats.
See this image and copyright information in PMC

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