Betty Gourdon1,2,3, Xavier Declèves4,5,6, Jean-Manuel Péan1, Caroline Chemin1. 1. Technologie Servier, 27 rue Eugène Vignat, Orléans, France. 2. Inserm, U1144, F-75006, Paris, France. 3. Faculté de Pharmacie de Paris, UMR-S 1144, Université Paris Descartes, F-75006, Paris, France. 4. Inserm, U1144, F-75006, Paris, France. xavier.decleves@parisdescartes.fr. 5. Faculté de Pharmacie de Paris, UMR-S 1144, Université Paris Descartes, F-75006, Paris, France. xavier.decleves@parisdescartes.fr. 6. Inserm UMR-S1144, Universités Paris Descartes et Paris Diderot, 4 avenue de l'observatoire, 75006, Paris, France. xavier.decleves@parisdescartes.fr.
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.
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.
Authors: Jianjun Cheng; Benjamin A Teply; Ines Sherifi; Josephine Sung; Gaurav Luther; Frank X Gu; Etgar Levy-Nissenbaum; Aleksandar F Radovic-Moreno; Robert Langer; Omid C Farokhzad Journal: Biomaterials Date: 2006-10-20 Impact factor: 12.479
Authors: Eric M Pridgen; Frank Alexis; Timothy T Kuo; Etgar Levy-Nissenbaum; Rohit Karnik; Richard S Blumberg; Robert Langer; Omid C Farokhzad Journal: Sci Transl Med Date: 2013-11-27 Impact factor: 17.956