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Organogel Nanoparticles as a New Way to Improve Oral Bioavailability of Poorly Soluble Compounds

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Abstract

Purpose

The aim of the study was to evaluate organogel nanoparticles as a lipophilic vehicle to increase the oral bioavailability of poorly soluble compounds. Efavirenz (EFV), a Biopharmaceutical Classification System (BCS) Class II, was used as drug model.

Methods

Organogel nanoparticles loaded with EFV were formulated with sunflower oil, 12-hydroxystearic acid (HSA) and polyvinyl alcohol (PVA). Various parameters have been investigated in the current study such as (i) the release profile of organogel assessed by USP 4 cell flow dialysis, (ii) the impact of organogel on intestinal absorption, using Caco-2 cells as in vitro model and jejunum segments as ex vivo assay and (iii) the bioavailability of organogel following oral pharmacokinetic study.

Results

250–300 nm spherical particles with a final concentration of 4.75 mg/mL drug loading were obtained, corresponding to a thousand fold increase in EFV solubility, combined to a very high encapsulation efficiency (>99.8%). Due to rapid diffusion, drug was immediately released from the nanoparticles. The biopharmaceutical evaluation on ex vivo jejunum segments demonstrated an increased absorption of EFV from organogel nanoparticles compare to a native EFV suspension. In vitro assays combining Caco-2 cell cultures with TEM and confocal microscopy demonstrated passive diffusion, while paracellular integrity and endocytosis activity remain expelled. Oral pharmacokinetics of EFV organogel nanoparticles improve oral bioavailability (Fr: 249%) and quick absorption compared to EFV suspension.

Conclusion

Organogel nanoparticles increase the bioavailability of BCS Class II drugs. The main phenomena is simply oil transfer from the gelled particles through the cell membrane.

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Abbreviations

API:

Active pharmaceutical ingredient

EFV:

Efavirenz

NR:

Nile Red

PVA:

Polyvinyl alcohol

HAS:

Hydroxystearic acid

DLS:

Dynamic Light Scattering

TEM:

Transmission electron microscopy

DSC:

Differential scanning calorimetry

EE:

Encapsulation efficiency

SGF:

Simulated gastric fluid

SIF:

Simulated intestinal fluid

Tmax:

Time to maximum concentration

Cmax:

Maximum plasma concentration

SD:

Standard deviation

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Authors and Affiliations

  1. Université de Toulouse, UPS/CNRS, IMRCP, Toulouse, France

    Baptiste Martin, Emile Perez & Sophie Franceschi

  2. Université Clermont Auvergne, INRAE, MEDIS, F-63000, Clermont-Ferrand, France

    Ghislain Garrait & Eric Beyssac

  3. Centre de Microscopie Electronique Appliquée à la Biologie, Faculté de Médecine Rangueil, 113 route de Narbonne, 31062, Toulouse Cedex, France

    Dominique Goudouneche

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  1. Baptiste Martin
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  2. Ghislain Garrait
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  4. Dominique Goudouneche
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Correspondence to Eric Beyssac.

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Martin, B., Garrait, G., Beyssac, E. et al. Organogel Nanoparticles as a New Way to Improve Oral Bioavailability of Poorly Soluble Compounds. Pharm Res 37, 92 (2020). https://doi.org/10.1007/s11095-020-02808-w

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