Abstract Reproduction Form
Deadline: November 1, 2003(To aid completion of the Abstract Form please refer to the instructions)
Title(Prof/Dr/Mr/Mrs/Ms)
Presenting author first name
Presenting author middle name
Presenting author last name
Company/University
Address
Postal Code
City
Country
Telephone No
Fax No
Type of presentation requested / Poster Podium
INSTRUCTIONS FOR SUBMISSION
Format of Abstract: One page, Font: Times New Roman, size 14, margin: Top= 3.2 cm, Bottom= 4.3 cm, Left= 3.5 cm, Right= 3.5 cma. The Abstract should be limited to the following sections:
- Purpose
- Methods
- Results
- Conclusions
b. Short specific titles should be used
c. Underline initials and last name of the author who will present the work
TYPING INSTRUCTIONS
a. The abstract must be clearly typed in ENGLISHb. The abstract form, when completed, should be sent by e-mail or disk to:
APGI 5 Rue Jean Baptiste Clément, F-92296 Châtenay-Malabry, France
. Return completed abstract form by June 15, 2003
COMBINED POLY (ALKYL CYANOACRYLATE)/ CYCLODEXTRIN NANOPARTICLES
Dominique Duchêne, Gilles Ponchel
UMR CNRS 8612, Faculty of Pharmacy, Paris-Sud University,
Châtenay Malabry, France
E-mail:
Purpose: To investigate the effect of cyclodextrins on the feasibility of preparing, in aqueous medium, of biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles loaded with water insoluble or poorly soluble drugs, intended for oral or parenteral administration.
Methods: Nanoparticles were prepared by anionic emulsion polymerisation of alkyl cyanoacrylate in the presence of poloxamer 188 and a cyclodextrin (α, β, γ-cyclodextrin, their hydroxypropyl derivatives, or β-cyclodextrin sulfobutyl ether) or an inclusion complex of a drug in a cyclodextrin (steroids or saquinavir)
Results: The smallest and most monodisperse unloaded nanoparticles are obtained with HP-β or γ-CD. The loading capacity of the steroids is increased 5 to 130-fold in the presence of a cyclodextrin. The drug is either dispersed molecularly or in amorphous state in the nanoparticles. Drug release was very fast up to a plateau, depending on the particle size and the nature of the medium. The presence of esterases in the medium allowed complete release of the drug. In the case of saquinavir, a 15-fold increase in loading capacity was obtained in the presence of HP-β-CD. Furthermore, 2.5 % dimethyl β-cyclodextrin added to the nanoparticle dispersion medium resulted in an increase in the apical/basolateral transport of saquinavir and a decrease in its basolateral/apical transport in Caco2 cell monolayers, indicating a probable increase in bioavailability.
Conclusion: The use of HPCDs in the formulation of PACA nanoparticles has a favourable effect on drug loading, and prolongs its release. Their high concentration at the nanoparticle surface suggests their role in the steric stabilisation of particles. The increase in drug loading could result from dissociation of the inclusion compound and entrapment of the free drug. The mechanism by which DM-β-CD increases the overall absorption of saquinavir by Caco 2 cell monolayers, thus counteracting the effect of pgP expression, has not yet been elucidated.