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Protein Therapeutics: Delivery

Protein Therapeutics: Delivery. Devin Hudson. Delivery Methods. Intravenously Subcutaneously Suppository Intranasally Orally * Transinfection *. Liquid Filled Nanoparticles as a Drug Delivery Tool.

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Protein Therapeutics: Delivery

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  1. Protein Therapeutics: Delivery Devin Hudson

  2. Delivery Methods • Intravenously • Subcutaneously • Suppository • Intranasally • Orally* • Transinfection*

  3. Liquid Filled Nanoparticles as a Drug Delivery Tool. Venkatesan, N., Yoshimitsu, J., Ito, Y., Shibata, N. Takada, K. (2005) Biomaterials. 26, 7154-7163.

  4. Barriers to Oral Bioavailability • Percent Bioavailability: BA% • Poor Membrane Permeability • Enzymatic Degradation • Past Attempts: liposomes, nanoparticles, micro-spheres, hydragels, mucoadhesives, micro-emulsions

  5. Concept

  6. Erythropoietin (EPO) Hormone: Produced in Kidneys Erythropoiesis 1BUY 1BUY 1BUY PDB: 1BUY

  7. Porous Absorbents Carbon Nano Tube Carbon Nanohorn Fullerenes Other Porous Substrates: Silicon Dioxide, Charcoal, bamboo charcoal

  8. Treatment Jejunum: large surface area Blood EPO measured via Jugular vein with ELISA

  9. Absorption Enhancers Formulation G: labrasol

  10. Porous Absorbents Formulation A: CNT

  11. Protease Inhibitors casein vs lactoferrin Formulation G: Casein

  12. Conclusion BA% = 11.5

  13. Systemic Delivery of Secreated Protein by Grafts of Epidermal Keratinocyctes: Prospects for Keratinocyte Gene Therapy. Fenjves, E. S., Smith, J., Zaradic, S. and Lorne, B. T. (1994) Human Gene Therapy. 5, 1241-1248 Wikipedia.org

  14. Concept Transfect with recombinant apoE-HA1 (pSV2neo) ELISA: Two Tests Graft skin Wikipedia.org

  15. Keratinocyctes and Aythmic Mice Stable Long Term Grafts Effectively Transduced via retrovirus Secretory tissue Newborn Foreskin Immune- deficient No Rejection Response Xenografts Wikipedia Nude Mouse

  16. Fractionation – Ficoll 400 Non-fractionated: total Small: basal compartment rich Intermediate: poorly characterized Large: terminally differentiated suprabasal cells Basal compartment keratinocyctes excrete endogenous apoE Mature Differentiated keratinocyctes do not excrete endogenous apoE Recomibant apoE expressed by any transfected keratinocytes

  17. Long Term Success Blood Serum apoE after 28 days Previous work: Viral promoters shut off over time

  18. Conclusion Higher Recombinant Expression in vivo Expansion in suprabasal cells in grafts Estimated that graft covering 2% of human skin could provide 6.5-8.9mg of recombinant protein per day.

  19. Oral vs Graft Pros: Doesn’t Require On-Going Care Lower Long Term Expense Less Margin for Patient Error Less Risky than Systemic Transfection Cons: Invasive Treatment Can Not be Stopped Easily Pros: Easily Manage Dosing Quit/Start/Change Treatment Minimally Invasive Lower Short Term Expense Cons: Require On-going Care Suffer from Varied Absorption

  20. Refrences • Skin Patch • Fenjves, E. S., Smith, J., Zaradic, S. and Lorne, B. T. (1994) Systemic Delivery of Secreated Protein by Grafts of Epidermal Keratinocyctes: Prospects for Keratinocyte Gene Therapy. Human Gene Therapy. 5, 1241-1248. • Review Paper • Leader, B., Baca, Q, J,. and Golan, D, E. (2008) Protein therapeutics: a summary and pharmacological classification. Nature Publishing Group. 7, 21-39. • Oral • Venkatesan, N., Yoshimitsu, J., Ito, Y., Shibata, N. Takada, K. (2005) Liquid filled nanoparticles as a drug delivery tool. Biomaterials. 26, 7154-7163.

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