Protein Therapeutics Delivery Devin Hudson Delivery Methods Intravenously

Protein Therapeutics: Delivery Devin Hudson

Delivery Methods Intravenously Subcutaneously Suppository Intranasally Orally* * Transinfection

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

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

Concept

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

Porous Absorbents Carbon Nano Tube Carbon Nanohorn Fullerene s Other Porous Substrates: Silicon Dioxide, Charcoal, bamboo charcoal

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

Absorption Enhancers Formulation G: labrasol

Porous Absorbents Formulation A: CNT

Protease Inhibitors casein vs lactoferrin Formulation G: Casein

Conclusion BA% = 11. 5

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

Concept Transfect with recombinant apo. E-HA 1 (p. SV 2 neo) ELISA: Two Tests Graft skin Wikipedia. org

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

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

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

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. 9 mg of recombinant protein per day.

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

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.