1 / 36

Dissolving Microneedles for Transdermal Drug Delivery

Dissolving Microneedles for Transdermal Drug Delivery. Jeong Woo Lee, Jung-Hwan Park, Mark R. Prausnitz. 22 Oct 2008 Graduate Student Colloquium 2008 Chemical and Biomolecular Engineering Georgia Institute of Technology. Outline. Drug Market Transdermal Drug Delivery Route

hallie
Télécharger la présentation

Dissolving Microneedles for Transdermal Drug Delivery

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Dissolving Microneedles for Transdermal Drug Delivery Jeong Woo Lee, Jung-Hwan Park, Mark R. Prausnitz 22 Oct 2008 Graduate Student Colloquium 2008 Chemical and Biomolecular Engineering Georgia Institute of Technology

  2. Outline Drug Market Transdermal Drug Delivery Route Dissolving Microneedles Conclusion

  3. Biopharmaceuticals Market Public Biotech Sales and R&D Sales ($ billions) R&D Expense ($ billions) Nat. Biotech. 23 (1466) 2005

  4. Biopharmaceuticals Delivery Oral Delivery Injection Delivery

  5. Injection Delivery

  6. Skin Small MW and moderately lipophilic High MW and hydrophilic Epidermis(Stratum corneum + Viable epidermis) Dermis Hypodermis (Subcutaneous tissue) From www.antbits.co.uk

  7. Microneedle • Patent by Alza Corp. in 1971 • Microfabrication technique 100 mm

  8. Dissolving Microneedle “Dissolvable microneedles encapsulating biomolecules” Stratum Corneum Viable Epidermis Dermis

  9. Dissolving Microneedle • Advantages • Patient compliance • Self-administration • No sharp and biohazardous waste • Solid platform for biopharmaceuticals • Controllable delivery

  10. Key Questions • Fabrication • Mechanical Strength • Drug Delivery • Drug Stability

  11. Fabrication (1) • Material Selection • Safety in use • Biocompatibility • FDA-approved for injection • Mechanical property • Reliable insertion • Support for biomolecules integrity • Capability of aqueous process • Mild process conditions

  12. Polysaccharide

  13. Fabrication (2) Hydrogel Centrifugal Force Solidified Hydrogel Inverse Mold • Centrifugal casting • Aqueous drying process • External centrifugal force • Reliable mass production

  14. Fabrication (3) • Matrix • Carboxymethyl Cellulose (CMC) • Amylopectin • Drug only • BSA B A D C 600 µm A: Master Structure B: CMC C: Amylopectin D: BSA

  15. Key Questions • Fabrication • Mechanical Strength • Drug Delivery • Drug Stability

  16. Mechanical Strength (A) Force-Displacement Measurement (B) Thumb-Push Demonstration Pig Skin Metal Surface

  17. Mechanical Strength (A) • Force-Displacement • Sudden yield for high aspect ratio • Yield at lower force for CMC Microneedles

  18. Failure Simulation • Critical Buckling Load (Pcri) • Low aspect ratio  16-fold increase • Large cross area  2-fold increase

  19. Mechanical Strength (A) • Force-Displacement • No sudden yield for low aspect ratio 2:1 4:1

  20. Mechanical Strength (A) • Force-Displacement • Similar behavior with other material

  21. Mechanical Strength (B) • Thumb-Push • Reliable insertion (Pig skin) • 150-200 µm insertion depth • Rapid dissolution of microneedles 150 µm Backside Tissue Staining Histology

  22. Dissolving Microneedles Before 10 sec 1 min 15 min 60 min

  23. Key Questions • Fabrication • Mechanical Strength • Drug Delivery • Drug Stability

  24. Drug Delivery Strategy • If drug is encapsulated in • Microneedles  Bolus release • Backing layer  Sustained release BolusRelease Sustained Release

  25. Bolus Delivery (1) • Bolus Release • Two-step casting • Limited dose (a few µg per needle) • 1 hour application time stratum corneum 600 µm 200 µm

  26. Sustained Release • Sustained Release • Two-step casting • High dose to milligrams • Adjustable release kinetics 600 µm 1 mm After 12 h

  27. In vitro Release • Controllable Release • Type of matrix material Sampling Port skin Receptor Chamber Stir bar Cumulative amount of the released drug (mg) Time (Day)

  28. In vitro Release • Controllable Release • Loading amount Sampling Port skin Receptor Chamber Stir bar Cumulative amount of the released drug (µg) Time (Hour)

  29. Key Questions • Fabrication • Mechanical Strength • Drug Delivery • Drug Stability

  30. Drug Stability • Lysozyme • Circular Dichroism (Secondary Structure) • Functional Activity (Tertiary Structure) • Human Growth Hormone (hGH) • Functional Activity (Tertiary structure) • Pharmacokinetics (In vivo)

  31. Drug Stability (Lysozyme) • Heat Denatured, Negative control, Lysozyme microneedles, Lysozyme Microneedles (two months storage), CMC + Lysozyme Circular Dichroism Functional Activity

  32. Drug Stability (hGH) • Cell population depending on the conc. of hGH • No activity loss of the encapsulated hGH

  33. hGH Pharmacokinetics • Placebo microneedles and hGH microneedles • Bolus hGH release in 6 hours hGH microneedles

  34. Conclusion • Polysaccharide microneedles dissolved inside the skin after the insertion, enabling two different delivery strategies: bolus and sustained delivery • CMC dissolving microneedles encapsulated protein drugs, lysozyme and human growth hormone, without the loss of drug stability.

  35. Acknowledgment • Thesis Committee • Dr. Mark Prausnitz, Dr. Mark Allen, Dr. Yulin Deng, Dr. Eric Felner, Dr. Lakeshia Taite • Microneedle Fabrication • Dr. Seong-O Choi • Cell Group of Drug Delivery Lab • Dr. Robyn Schlicher, Ying Liu, Prerona Chakravarty, Joshua Hutcheson • hGH Pharmacokinetics • Dr. Laura O’Farrell, Jae hyung Park • Funding from NIH

  36. Q&A

More Related