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Spray dried mebendazole–loaded Soluplus-based polymeric micelles for improved biopharmaceutical attributes: in vitro and in vivo studies

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Abstract

The aim of this research was to investigate spray-dried mebendazole (MBZ)–loaded Soluplus-based polymeric micelles (MBZ@PMs) for improved solubility and bioabsorption upon oral administration. Following the MBZ@PM preparation, the formed micellar preparation was examined using FTIR, PXRD, DSC, and TEM techniques to determine its physical and chemical properties. Critical micelle concentration determination studies showed that Soluplus® can effectively generate stable polymeric micelles. Particle size analysis demonstrated spherical shape and a particle size of 538.7 ± 2.129 nm. Solubility studies demonstrated approximately eight times higher solubility of MBZ@PMs vis-à-vis MBZ in PBS pH 6.8 (90.16 ± 2.54 µg/mL v/s 11.97 ± 2.99 µg/mL). Stability studies confirmed that the size distribution and polydispersity index of the prepared polymeric micelles showed negligible variations. In vitro release studies revealed low MBZ release from MBZ@PMs (9.70 ± 3.2% in 2 h) at pH 1.2 and sustained (33.3 ± 3.9%) at PBS pH 6.8 in 48 h. In vivo pharmacokinetic studies showed approximately fourfold higher bioavailability (AUC0-ꝏ 153.81 ± 24.20 v/s 38.20 ± 5.55) and 1.5-fold extended half-life of MBZ from MBZ@PMs (2.13 ± 0.53 v/s 1.44 ± 0.36). Therefore, these unprecedented Soluplus®-based polymeric micelles of Mebendazole can be applied as a potential carrier system to improve the therapeutic efficacy of poorly water-soluble compounds.

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The entire information (and measurements) produced while experimenting is incorporated in the manuscript.

Abbreviations

MBZ:

Mebendazole

MBZ@PMs:

Mebendazole-loaded Soluplus®-based polymeric micelles

PM/PMs:

Polymeric micelles

CMC:

Critical micelle concentration

MBZ@ZIF-8:

Mebendazole-loaded Zeolitic Imidazolate Framework-8

TEM:

Transmission electron microscopy

FTIR:

Fourier transform infrared spectroscopy

DSC:

Differential scanning calorimetry

PXRD:

Powder X-ray diffraction

HPLC:

High-performance liquid chromatography

DI:

Deionized

DL:

Drug loading

EE:

Entrapment efficiency

PDI:

Polydispersity index

I2 :

Iodine

KBr:

Potassium bromide

IAEC:

Institutional Animal Ethics Committee

RH:

Relative humidity

ACN:

Acetonitrile

C max :

Maximum concentration

T max :

Time to reach maximum concentration

AUC:

Area under the curve

t 1/2 :

Elimination half-life

MRT:

Mean residence time

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Acknowledgements

The authors are tremendously obliged to ISF College of Pharmacy, Moga, and IK Gujral Punjab Technical University, Kapurthala, Punjab, for equipping the laboratories with the required instrumentation (Spray dryer (SPD-P-111), FTIR, and DSC instrumentation) and research space to conduct the experiment. Besides, the authors also acknowledge the Panjab University, Chandigarh, for carrying out the PXRD analysis and Punjab Agricultural University, Ludhiana, for allowing the execution of TEM for the morphological analysis of the formulation. The authors duly acknowledge the Science and Engineering Research Board (SERB, GoI) for providing the necessary equipment (Spray Drying) to develop MBZ@PMs under the project EEQ/2020/000616.

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Authors and Affiliations

  1. IK Gujral Punjab Technical University, Kapurthala, Punjab, India

    Tania Bajaj

  2. Department of Pharmaceutics, ISF College of Pharmacy, IK Gujral Punjab Technical University, Moga, Jalandhar, Punjab, 142001, India

    Tania Bajaj, Ghanshyam Das Gupta & Charan Singh

  3. Department of Pharmaceutical Sciences, School of Sciences, Hemvati Nandan Bahuguna Garhwal University (A Central University), Srinagar Garhwal, Uttarakhand, 246174, India

    Charan Singh

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  1. Tania Bajaj
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Contributions

Every single author furnished the experimental formulation and execution. Tania Bajaj: executed the experimentation and documented the article. Charan Singh: co-supervision; designed the experiment and revised the article. Ghanshyam Das Gupta: supervision; designed the experiment and fundamentally looked into the manuscript. Each author has confirmed the data submitted in the manuscript.

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Correspondence to Ghanshyam Das Gupta or Charan Singh.

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Bajaj, T., Das Gupta, G. & Singh, C. Spray dried mebendazole–loaded Soluplus-based polymeric micelles for improved biopharmaceutical attributes: in vitro and in vivo studies. Colloid Polym Sci (2024). https://doi.org/10.1007/s00396-024-05251-0

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