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Tacrolimus-loaded chitosan-coated nanostructured lipid carriers: preparation, optimization and physicochemical characterization

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Abstract

Tacrolimus as an immunosuppressive drug shows poor solubility in aqueous media, accompanied by a low/variable bioavailability in peroral administration due to its high first-pass metabolism. Therefore, in this study, drug-loaded chitosan-coated nanostructured lipid carriers (CCNLCs) were prepared to overcome these limitations. Tacrolimus-loaded NLCs were prepared via solvent displacement technique and were optimized. Stearic acid (SA) and glyceryl mono stearate (GMS) were used as solid lipids, oleic acid (OA) and tween 80 were used as liquid lipid and stabilizer, respectively, in the structure of NLC. The prepared nanoparticles were characterized by size and zeta potential measurements, drug loading determinations, scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) analysis. Release profile of tacrolimus from NLCs and CCNLCs was also studied. The results indicated the effect of some preparation parameters on particle size as a dependent parameter. The selected formulations had particle sizes under 100 nm. Conversion of negative zeta potential of NLCs into positive quantities in CCNLCs was attributed to the effect of chitosan coating. SEM images of nanocarriers proved nanoscale dimensions and FTIR analysis showed no unwanted chemical reactions between drug and excipients. NLCs and CCNLCs released the drug in a sustained release pattern. However, chitosan-coating attenuated the burst effect and caused more extended release. The results of this study demonstrated formation of tacrolimus-loaded NLCs and coating them with chitosan with desirable characteristics. These findings suggested that this carrier is a good candidate to overcome serious bioavailability problems of common peroral formulations of tacrolimus.

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Abbreviations

NLC:

Nanostructured lipid carriers

CCNLCs:

Chitosan-coated nanostructured lipid carriers

SA:

Stearic acid

GMS:

Glyceryl mono stearate

OA:

Oleic acid

SEM:

Scanning electron microscopy

FTIR:

Fourier transform infrared spectroscopy

BCS:

Biopharmaceutical classification system

PEG:

Polyethylene glycol

DLE:

Drug-loading efficiency

EE:

Entrapment efficiency

PBS:

Phosphate-buffered saline

HLB:

Hydrophilic–lipophilic balance

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Funding

This work was funded by Dean of Research, Ardabil University of Medical Sciences as a PharmD thesis number 527. The authors would like to appreciate from this support.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, 5618953141, Ardabil, Iran

    Somayeh Dasineh, Maryam Akbarian & Hossein Ali Ebrahimi

  2. Department of Chemical Engineering, Faculty of Engineering, University of Mohaghegh Ardabili, Ardabil, Iran

    Gity Behbudi

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  1. Somayeh Dasineh
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  2. Maryam Akbarian
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  3. Hossein Ali Ebrahimi
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  4. Gity Behbudi
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SD and MA carried out the experiments and collected the data. HAE conceived the idea of this study, supervised the experiments and wrote the manuscript and GB performed the experimental analysis.

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Correspondence to Hossein Ali Ebrahimi.

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This research was approved by ethical committee of Ardabil University of Medical Sciences under the Approval ID: IR.ARUMS.REC.1398.292.

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Dasineh, S., Akbarian, M., Ebrahimi, H.A. et al. Tacrolimus-loaded chitosan-coated nanostructured lipid carriers: preparation, optimization and physicochemical characterization. Appl Nanosci 11, 1169–1181 (2021). https://doi.org/10.1007/s13204-021-01744-4

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