title: Erythropoietin-coated ZP-microneedle transdermal system: preclinical formulation, stability, and delivery.
abstract: OBJECTIVE
  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.
authors.affiliation: Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California 94555, USA.
authors.forename: Elaine E
authors.initials: EE
authors.lastname: Peters
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ameri
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Yuh-Fun
authors.initials: YF
authors.lastname: Maa
authors.forename: Peter E
authors.initials: PE
authors.lastname: Daddona
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D020099:Coated Materials, Biocompatible; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004355:Drug Stability; D000068817:Epoetin Alfa; D004867:Equipment Design; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D005240:Feasibility Studies; D006397:Hematinics / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008904:Miniaturization; D009339:Needles; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D012212:Rheology; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013678:Technology, Pharmaceutical / Q000379:methods; D014025:Titanium; D014783:Viscosity
chemical_list: D020099:Coated Materials, Biocompatible; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D014025:Titanium