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Double or Simple Emulsion Process to Encapsulate Hydrophilic Oxytocin Peptide in PLA-PEG Nanoparticles

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Abstract

Purpose

Oral drug delivery using NPs is a current strategy for poorly absorbed molecules. It offers significant improvement in terms of bioavailability. However, the encapsulation of proteins and peptides in polymeric NPs is a challenge. Firstly, the present study focused on the double emulsion process in order to encapsulate the OXY peptide. Then the technique was challenged by a one-step simplified process, the simple emulsion.

Methods

In order to study the influence of formulation and process parameters, factorial experimental designs were carried on. The responses observed were the NP size (<200 nm in order to penetrate the intestinal mucus layer), the suspension stability (ZP < |30| mV) and the OXY loading.

Results

It was thus found that the amount and the nature of surfactant, the ratio between the phases, the amount of PLA-PEG polymer and OXY, the presence of a viscosifying agent, and the duration of the sonication could significantly influence the responses. Finally, OXY-loaded NPs from both processes were obtained with NP size of 195 and 226 nm and OXY loading of 4 and 3.3% for double and simple emulsions, respectively.

Conclusion

The two processes appeared to be suitable for OXY encapsulation and comparable in term of NP size, peptide drug load and release obtained.

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Abbreviations

ACN:

Acetonitrile

ATFA:

Trifluoroacetic acid

BSA:

Bovine serum albumin

DCM:

Dichloromethane

DL:

Drug load

DLS:

Dynamic light scattering

DMSO :

Dimethyl sulfoxyde

EtAc:

Ethyl acetate

EtOH:

Ethanol

HBSS:

Hanks buffer saline solution

HEC:

Hydroxy ethyl cellulose

HLB:

Hydrophilic-lipophilic balance

HPLC:

High pressure liquid chromatography

MES:

2-(N-morpholino)ethanesulfonic acid

NME:

New molecular entity

NP:

Nanoparticle

O:

Organic phase

OXY:

Oxytocin

PDLG:

DL-lactide/glycolide copolymer

PEG:

Poly-ethylene glycol

PLA:

Polylactic acid

PLGA:

Poly-D-L-lactide-co-glycolide

PVA:

Poly(vinyl alcohol)

W:

Aqueous phase

WE:

External aqueous phase

WI:

Internal aqueous phase

ZP:

Zeta potential

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Acknowledgments and Disclosures

The author reports no conflicts of interest in this work.

Author information

Authors and Affiliations

  1. Technologie Servier, 27 rue Eugène Vignat, Orléans, France

    Betty Gourdon, Jean-Manuel Péan & Caroline Chemin

  2. Inserm, U1144, F-75006, Paris, France

    Betty Gourdon & Xavier Declèves

  3. Faculté de Pharmacie de Paris, UMR-S 1144, Université Paris Descartes, F-75006, Paris, France

    Betty Gourdon & Xavier Declèves

  4. Inserm UMR-S1144, Universités Paris Descartes et Paris Diderot, 4 avenue de l’observatoire, 75006, Paris, France

    Xavier Declèves

Authors
  1. Betty Gourdon
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  2. Xavier Declèves
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  4. Caroline Chemin
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Corresponding author

Correspondence to Xavier Declèves.

Electronic supplementary material

Fig. S1

Apparent viscosity (Pas) of the viscofying agents HEC at 1% and 2.5% (w/v) and PEG 400 at (3:2) and (2:3) ratios with water, represented as function of shearing speed (1/s), in [water + poloxamer P188 1% (w/v)] aqueous phase (JPEG 83 kb)

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Gourdon, B., Declèves, X., Péan, JM. et al. Double or Simple Emulsion Process to Encapsulate Hydrophilic Oxytocin Peptide in PLA-PEG Nanoparticles. Pharm Res 35, 82 (2018). https://doi.org/10.1007/s11095-018-2358-9

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  • DOI: https://doi.org/10.1007/s11095-018-2358-9

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