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. 2021 Mar 21;13(6):960.
doi: 10.3390/polym13060960.

Leflunomide Sustained Skin Delivery Based on Sulfobetaine-Modified Chitosan Nanoparticles Embedded in Biodegradable Polyesters Films

Stavroula G Nanaki  1 , Evi Christodoulou  1 , Nikolaos D Bikiaris  1 , Afroditi Kapourani  2 , Konstantinos N Kontogiannopoulos  2   3 , Souzan Vergkizi-Nikolakaki  4 , Panagiotis Barmpalexis  2   3
Affiliations

Leflunomide Sustained Skin Delivery Based on Sulfobetaine-Modified Chitosan Nanoparticles Embedded in Biodegradable Polyesters Films

Stavroula G Nanaki et al. Polymers (Basel). .

Abstract

The aim of the present study was to prepare a leflunomide (LFD) sustained release transdermal delivery system for the treatment of psoriasis. In this context, LFD-loaded nanoparticles (NPs) based on either neat chitosan (CS) or CS modified with [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SDAEM, a sulfobetaine zwitterionic compound) were initially prepared via ionotropic gelation and characterized in terms of in vitro dissolution, physicochemical, and antibacterial properties. Results showed that the use of the SDAEM-modified CS resulted in the formation of LFD-loaded NPs with improved wetting and solubilization properties, better in vitro dissolution profile characteristics (i.e., higher dissolution rate and extent), and improved (enhanced) antibacterial properties. The resultant LFD-loaded NPs were then embedded in suitable thin-film skin patches, prepared via spin-coating, utilizing two different biodegradable polyesters, namely methoxy polyethylene glycol-b-poly(L-lactide) (mPEG-b-PLA, at a ratio of 25/75 mPEG to PLA) and poly(lactic-co-glycolic acid) (PLGA at a ratio of 75/25 DL-lactide/glycolide copolymer). Results showed the formation of polymeric thin-films with no agglomeration (or trapped air) and uniform structure in all cases, while the LFD-loaded NPs were successfully embedded in the polymeric matrix. Analysis of the obtained in vitro dissolution profiles revealed a sustained release profile of the drug for up to approximately twelve days, while between the two proposed systems, the use of CS-SDAEM NPs (independently of the polyester type) was the most promising formulation approach.

Keywords: PLGA; SDAEM-grafting; biodegradable polyesters; chitosan; ionotropic gelation; leflunomide; mPEG-b-PLA; nanoparticles; spin coating; thin-film patches.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
LDF chemical structure.
Scheme 1
Scheme 1
Chemical reaction followed during the synthesis of SDAEM-modified CS.
Scheme 2
Scheme 2
Chemical reaction followed during the synthesis of mPEG-b-PLA.
Figure 2
Figure 2
1H-NMR spectra (a) and FT-IR spectra (b) of CS, SDAEM and CS-SDAEM.
Figure 3
Figure 3
pXRD diffractograms (a) and swelling profile (b) of CS, SDAEM, and CS- SDAEM.
Figure 4
Figure 4
SEM images of CS-LFD (a) and CS-SDAEM-LFD (b) NPs.
Figure 5
Figure 5
DSC thermograms (a) and pXRD diffractograms (b) of LFD loaded CS and CS-SDAEM NPs.
Figure 6
Figure 6
FT-IR spectra (a) and in vitro dissolution profile (b) of LFD loaded CS and CS-SDAEM NPs.
Figure 7
Figure 7
1H-NMR (a) and FT-IR spectra (b) of mPEG-b-PLA and monomers.
Figure 8
Figure 8
DSC thermogram (a), pXRD diffractograms (b), and TGA thermogram (c) of mPEG-b-PLA.
Figure 9
Figure 9
DSC thermogram of mPEG-b-PLA and PLGA thin-films with LFD-loaded NPs.
Figure 10
Figure 10
pXRD diffractograms of mPEG-b-PLA and PLGA thin-films with LFD-loaded NPs.
Figure 11
Figure 11
FT-IR spectra of mPEG-b-PLA and PLGA thin-films with LFD-loaded NPs.
Figure 12
Figure 12
Full in vitro dissolution profile (a) and initial burst release (b) of mPEG-b-PLA and PLGA thin-films with LFD-loaded NPs.
Figure 13
Figure 13
Degree of swelling vs. time of mPEG-b-PLA and PLGA thin-films with LFD-loaded NPs.
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