Applications of Nanoparticles for Delivery of Therapeutic Agents

1. Applications of Nanoparticles for Delivery of Therapeutic Agents Frank Jeyson Hernández Topics of Nanobiotechnology 30 June, 2004

2. Introduction Significant effort has been devoted to develop nanotechnology for drug delivery since it offers a suitable means of delivering small molecular weight drugs, as well as macromolecules such as proteins, peptides or genes. [1] Advanced Drug Delivery Reviews 55 (2003) 329–347.

3. Introduction Nanotechnology focuses on formulating therapeutic agents in biocompatible nanocomposites such as: Nanoparticles Nanocapsules Micellar systems [1] Advanced Drug Delivery Reviews 55 (2003) 329–347.

4. Introduction These systems can be used to provide targeted (cellular / tissue) delivery of drugs. Improve oral bioavailability, to solubilize drugs for intravascular delivery, and to improve the stability of therapeutic agents against enzymatic degradation. [1] Advanced Drug Delivery Reviews 55 (2003) 329–347.

5. 6µm 60 nm Nanoparticles [2]World Journal of Gastroenterology 2004;10(1):112-116 The nanometer size-ranges of these delivery systems offer certain distinct advantages for drug delivery. Due to their sub-cellular and sub-micron size, nanoparticles can penetrate deep into tissues through fine capillaries, cross the fenestration present in the epithelial lining. [1] Advanced Drug Delivery Reviews 55 (2003) 329–347.

6. Intracellular Trafficking Nanoparticles are internalized efficiently through an endocytic process and that uptake is concentration- and time-dependent. Efficiency decreased at higher doses, suggesting that the pathway is saturable. [1] Advanced Drug Delivery Reviews 55 (2003) 329–347.

7. Intracellular Trafficking Following their uptake, nanoparticles are transported through early endosomes. A fraction of nanoparticles recycles back to the cell exterior while another fraction is transported to secondary endosomes/lysosomes from where nanoparticles escape into the cytoplasm. Nanoparticles that escape into the cytoplasm could act as intracellular reservoirs for sustained release of the encapsulated therapeutic agent. [1] Advanced Drug Delivery Reviews 55 (2003) 329–347.

8. Therapeutic Application of Nanoparticles Nanoparticles containing DNA DNA Released Nucleus • Sustained Gene Delivery Rapid escape of nanoparticles from the degradative endo-lysosomal compartment to the cytoplasmic compartment and their sustained intracellular retention suggest that nanoparticles containing capsulated plasmid DNA could serve as an efficient sustained release gene delivery system. [1] Advanced Drug Delivery Reviews 55 (2003) 329–347. The generating a nonviral gene delivery vehicle is reached. [5] http://www.unmc.edu/pharmacy/ labhasetwar/images/fig3.gif [3] Journal of Controlled Release 92 (2003) 199–208

9. Therapeutic Application of Nanoparticles • Vaccine Adjuvant The vaccine adjuvant is effective and safe, which could also reduce the frequency of immuniation. The nanospheres induce a systemic immune response, which is almost comparable to the immune response induced using alum as an adjuvant. [6] J. Microencapsulation, 2000, VOL. 17, NO. 2, 215 ± 225. [6] J. Microencapsulation, 2000, VOL. 17, NO. 2, 215 ± 225. The scanning electron micrograph of nanospheres containing Staphylococcal Enterotoxin B.

10. Tissue Targeting • Targeted Drug Delivery Systems Recent advances in biotechnology have enabled a whole new generation of drug delivery systems in which the drug is targeted to a specific site using a recognition such as an antibody. This approach has been fairly successful, resulting in drug products such as sustained-release formulations, transdermal patches, liposomes and other colloidal delivery systems [4] http://lysine.pharm.utah.edu/pceu_web/herron.htm [4] http://lysine.pharm.utah.edu/pceu_web/herron.htm

11. Tissue Targeting • Liposomes The liposomal drug carriers which are coated with both antibody fragments (Fab) and poly(ethylene glycol)(PEG). The Fab fragments serve as recognition for to direct the liposomes to target cells such as lymphomas, while the PEG molecules enable the liposomes to "hide" from the reticular endothelial system (RES) Liposome filled with target drug [4] http://lysine.pharm.utah.edu/pceu_web/herron.htm [7] http://tubs.sa.utoronto.ca/pandp.htm

12. Conclusions • The nanoparticles are a potentially useful drug delivery system capable of delivering a multitude of therapeutic agents by targeted and/or sustained delivery. • Also, as the pathophysiology of disease conditions and their cellular mechanisms are understood, drug delivery systems customized to achieve optimal therapeutic efficacy will be more effective. • The versatility of nanoparticles for formulation, sustained release properties, sub-cellular size and biocompatibility with tissue and cells appear to be a promising system to achieve these important objectives.

13. References [1] Jayanth Panyam , Vinod Labhasetwar, Biodegradable nanoparticles for drug and gene delivery to cells and tissue, Advanced Drug Delivery Reviews 55 (2003) 329–347. [2] Jing Chen, Wu-Li Yang, Ge Li, Ji Qian, Jing-Lun Xue, Transfection of mEpo gene to intestinal epithelium in vivo mediated by oral delivery of chitosan-DNA nanoparticles, World J Gastroenterol 2004;10(1):112-116. [3] Stephanie Rhaese, et. al., H uman serum albumin–polyethylenimine nanoparticles for gene delivery, Journal of Controlled Release 92 (2003) 199–208. [4] http://lysine.pharm.utah.edu/pceu_web/herron.htm [5]http://www.unmc.edu/pharmacy/labhasetwar/images/fig3.gif [6] Immune response with biodegradable nanospheres and alum: studies in rabbits using staphylococcal enterotoxin B-toxoid, M. P. Desai,J. Microencapsulation, 2000, VOL. 17, NO. 2, 215 ± 225. [7] http://tubs.sa.utoronto.ca/pandp.htm

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