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Nanoparticulate drug delivery systems

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Presentation on theme: "Nanoparticulate drug delivery systems"— Presentation transcript:

1 Nanoparticulate drug delivery systems
A. Lamprecht Nanoparticulate drug delivery systems for different therapeutic applications Alf Lamprecht Laboratory of Pharmaceutical Engineering (EA3924), University of Franche-Comté, Besançon, France Contact: Concours "Avenir 2001"

2 A. Lamprecht Concours "Avenir 2001"

3 A. Lamprecht “Le Menu” Nanoparticles for the absorption of drugs with low bioavailability (oral heparin) Nanoparticles for the selective drug targeting (inflammatory bowel disease) Nanocapsules for intracellular drug therapy (cancer) drug intestinal barrier organs cells, receptors B C A Concours "Avenir 2001"

4 polymeric nanoparticles and their therapeutic applications
A. Lamprecht polymeric nanoparticles and their therapeutic applications Nanoparticles for oral delivery of macromolecules Objective: enhanced absorption of the drug transport across biological barrier avoidance of repetitive injections Concours "Avenir 2001"

5 Nanoparticles for oral absorption
A. Lamprecht Nanoparticles for oral absorption Heparin - anionic glycosaminoglycans - treatment and prophylaxis of venous thrombosis parenteral administration no oral absorption  do not pass the intestinal barrier NANOPARTICLES: drug entrapment (protection) emulsion techniques biocompatible polymers diameter: nm Concours "Avenir 2001"

6 Nanoparticles for oral absorption
A. Lamprecht Nanoparticles for oral absorption Formulations Cmax (s) Tmax (h) AUC/Kg (s.h/Kg) Absolute F (%) RL/PCL 20-27 6 28.3 ± 8.2 42.1 ± 12.3 RS/RL/PLGA 20-24 4-5 29.4 ± 12.6 43.9 ± 18.8 RS/PLGA 22-27 6-7 21.9 ± 18.4 32.7 ± 27.4 RL 19-27 3-6 26.3 ± 12.3 39.2 ± 18.3 IV UFH solution ND 67.1 ± 29.2 100 Pharmacokinetic parameters after oral administration of UFH-loaded NP (2000 IU) in rabbits (n=6) Concours "Avenir 2001"

7 Nanoparticles for oral absorption
A. Lamprecht Nanoparticles for oral absorption Cell culture model for adsorption studies: 1. Absorption barrier (cells) 2. Mucus ??? no influence on absorption kinetics of small drugs but macromolecules ??? adhesion studies on the cells, but adhesion to the mucus ???  mucoadhesion is the starting point!!! Concours "Avenir 2001"

8 Nanoparticles for oral absorption
A. Lamprecht Nanoparticles for oral absorption resonant mirror system: NP adhesion differs with surface charge Concours "Avenir 2001"

9 Nanoparticles for oral absorption
A. Lamprecht Nanoparticles for oral absorption mucin coated Caco-2 cells confluent but not homogeneous mucin layer stained with astra blue Aqueous boundary layer (ca. 40 µm) Mucus layer Epithelial cells Basolateral compartment Concours "Avenir 2001"

10 Nanoparticles for oral absorption
A. Lamprecht Nanoparticles for oral absorption cationic NP adhesion LMWH adhesion correlates!!! Concours "Avenir 2001"

11 Nanoparticles for oral absorption
A. Lamprecht Nanoparticles for oral absorption LMWH transport across mucin coated Caco-2 cell layers Concours "Avenir 2001"

12 Particle adhesion to Caco-2 cells
A. Lamprecht Conclusion Particle adhesion to Caco-2 cells Concours "Avenir 2001"

13 Nanoparticle targeting
A. Lamprecht Nanoparticle targeting in inflammatory bowel disease Objective: local drug delivery in IBD treatment targeting on tissue level lower adverse effects by a selective drug release Concours "Avenir 2001"

14 Inflammatory bowel disease
A. Lamprecht Inflammatory bowel disease chronic, relapsing inflammation of the colon unknown etiology swelling and ulceration of mucosa and submucosa therapeutic principles: induce remission of outbreaks prevent outbreaks during remission drug treatment oral (standard) rectal (limited use) intravenous (recent) surgery ulcerative colitis Crohn’s disease Concours "Avenir 2001"

15 Nanoparticles in colitis
A. Lamprecht Nanoparticles in colitis Histology of the inflamed colonic mucosa (TNBS-model for the rat) healthy control colitis group increases mucus production colitis group with ulcerated tissue Concours "Avenir 2001"

16 Nanoparticles in colitis
A. Lamprecht Nanoparticles in colitis Localization of 100nm particles in the colon healthy control mucus layer of colitis group ulcerated tissue of colitis group TNBS intrarectal; 5 days particles orally Concours "Avenir 2001"

17 Nanoparticles in colitis
A. Lamprecht Nanoparticles in colitis higher deposition in inflamed colon  selectivity size dependent accumulation no influence on the deposition in other gut regions Concours "Avenir 2001"

18 Nanoparticles in colitis
A. Lamprecht Nanoparticles in colitis tacrolimus: (also FK-506 or Fujimycin) use in organ transplant immunosuppressive use in IBD Concours "Avenir 2001"

19 Nanoparticles in colitis
A. Lamprecht Nanoparticles in colitis NP efficient after rectal administration  significant drug loss during intestinal transit Concours "Avenir 2001"

20 Nanoparticles in colitis
A. Lamprecht Nanoparticles in colitis solution: inflamed healthy NP: inflamed healthy NP increase drug tissue penetration selectively Concours "Avenir 2001"

21 Nanoparticles in colitis
A. Lamprecht Nanoparticles in colitis P-gp CYP NP tissue penetration into inflamed tissue into healthy tissue Concours "Avenir 2001"

22 Conclusion Nanoparticles target the inflamed tissue in IBD
A. Lamprecht Conclusion Nanoparticles target the inflamed tissue in IBD A) accumulate the drug in the inflamed tissue: B) increase and selectivity of drug tissue penetration I) high therapeutic efficiency II) reduction of adverse effects Concours "Avenir 2001"

23 Lipid nanocapsules and their therapeutic applications
A. Lamprecht Lipid nanocapsules and their therapeutic applications Nanocapsules in the treatment of cancer Objective: local drug delivery of anticancer drugs targeting on cell level higher efficiency by a selective drug release Concours "Avenir 2001"

24 Lipid nanocapsule preparation
A. Lamprecht Lipid nanocapsule preparation controlled drug release controlled surfactant release (P-gp inhibitor) slower release for higher drug loading Concours "Avenir 2001"

25 Nanocapsules in cancer
A. Lamprecht Nanocapsules in cancer in-vitro testing of LNC on glioma cell cultures: etoposide LNC up to 80-fold more potent more effective in F98 cells Concours "Avenir 2001"

26 Nanocapsules in cancer
A. Lamprecht Nanocapsules in cancer Confocal laser scanning microscopy LNC uptake in F98 (a) and 9L (b) cells etoposide + blank LNC no effect  cellular uptake required !!! Concours "Avenir 2001"

27 Nanocapsules in cancer
A. Lamprecht Nanocapsules in cancer Proposed mechanism of action: Concours "Avenir 2001"

28 Nanocapsules in cancer
A. Lamprecht Nanocapsules in cancer LNC - an promising concept in cancer treatment ? - intracellular uptake - drug release - PEG-HS release - potentially blocking the P-gp  overcoming the multidrug resistance ??? Concours "Avenir 2001"

29 Acknowledgments Angers J.P. Benoît F. Lacoeuille E. Garcion Gifu
A. Lamprecht Acknowledgments Angers J.P. Benoît F. Lacoeuille E. Garcion Gifu Y. Kawashima H. Takeuchi Yamamoto Nancy P. Maincent N. Ubrich Y. Meissner Saarbrücken C.M. Lehr U. Schäfer D. Neumann T. Betz Concours "Avenir 2001"

30 Acknowledgements - Japanese Society for the Promotion of Science
A. Lamprecht Acknowledgements - Japanese Society for the Promotion of Science - Alexander-von-Humboldt Foundation Monbugakushō Egide Fujisawa Pharmaceutical Co. Ltd. Concours "Avenir 2001"

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