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Erythropoietin-Coated ZP-Microneedle Transdermal System: Preclinical Formulation, Stability, and Delivery

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ABSTRACT

Purpose

To evaluate the feasibility of coating formulated recombinant human erythropoietin alfa (EPO) on a titanium microneedle transdermal delivery system, ZP-EPO, and assess preclinical patch delivery performance.

Methods

Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. EPO liquid formulation was coated onto titanium microneedles by dip-coating and drying. Stability of coated EPO was assessed by SEC-HPLC, CZE and potency assay. Preclinical in vivo delivery and pharmacokinetic studies were conducted in rats with EPO-coated microneedle patches and compared to subcutaneous EPO injection.

Results

Studies demonstrated successful EPO formulation development and coating on microneedle arrays. ZP-EPO patch was stable at 25°C for at least 3 months with no significant change in % aggregates, isoforms, or potency. Preclinical studies in rats showed the ZP-EPO microneedle patches, coated with 750 IU to 22,000 IU, delivered with high efficiency (75–90%) with a linear dose response. PK profile was similar to subcutaneous injection of commercial EPO.

Conclusions

Results suggest transdermal microneedle patch delivery of EPO is feasible and may offer an efficient, dose-adjustable, patient-friendly alternative to current intravenous or subcutaneous routes of administration.

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ACKNOWLEDGMENTS & DISCLOSURES

The authors would like to thank Joseph A. Bravo, James A. Matriano for assistance in the pharmacokinetic studies, Perry Weissburg, Shelly Fan, Scott Sellers for their contribution to the analytical analyses and Kenneth Chan for formulation preparation and SEM analyses.

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Author notes

  1. Xiaomei Wang

    Present address: MAP Pharmaceuticals, 2400 Bayshore Parkway, Suite 200, Mountain View, California, 94043, USA

  2. Yuh-Fun Maa

    Present address: Genentech, Inc, 1 DNA Way, South San Francisco, California, 94080, USA

Authors and Affiliations

  1. Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555, USA

    Elaine E. Peters, Mahmoud Ameri & Peter E. Daddona

Authors
  1. Elaine E. Peters
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  2. Mahmoud Ameri
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  3. Xiaomei Wang
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  4. Yuh-Fun Maa
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  5. Peter E. Daddona
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Corresponding author

Correspondence to Peter E. Daddona.

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Peters, E.E., Ameri, M., Wang, X. et al. Erythropoietin-Coated ZP-Microneedle Transdermal System: Preclinical Formulation, Stability, and Delivery. Pharm Res 29, 1618–1626 (2012). https://doi.org/10.1007/s11095-012-0674-z

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  • DOI: https://doi.org/10.1007/s11095-012-0674-z

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