title: Preparation, drug release, and cell growth inhibition of a gelatin: doxorubicin conjugate.
abstract: OBJECTIVE
  To demonstrate the feasibility of a novel macromolecular delivery system for doxorubicin (DOX) which combines pH dependent DOX release with a high molecular weight and biodegradable gelatin carrier.
  
  
  METHODS
  DOX was conjugated to gelatin using an acid labile hydrazone bond and a glycylglycine linker. The gelatin-doxorubicin conjugate (G-DOX) was evaluated for hydrazide and DOX content by spectrophotometry, molecular weight by HPLC-SEC, in vitro DOX release at various pH, and cell growth inhibition using EL4 mouse lymphoma and PC3 human prostate cells.
  
  
  RESULTS
  G-DOX hydrazide and DOX content was 47% and 5-7%, respectively of theoretical gelatin carboxylic acid sites. During preparation of G-DOX, the molecular weight decreased to 22 kDa. DOX release was 48% in pH 4.8 phosphate buffer, 22% at pH 6.5, but 10% at pH 7.4. The G-DOX IC50 values in EL4 and PC3 cells were 0.26 μM and 0.77 μM, respectively; the latter value 3 times greater than that of free DOX.
  
  
  CONCLUSIONS
  A 22 kDa macromolecular DOX conjugate containing 3.4-5.0% w/w DOX has been prepared. The pH dependent drug release in combination with a biodegradable gelatin carrier offer potential therapeutic advantages of enhanced tumor cell localization and reduced systemic toxicities of the drug.
authors.affiliation: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Darren C
authors.initials: DC
authors.lastname: Wu
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cammarata
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Brian T
authors.initials: BT
authors.lastname: Rhodes
authors.forename: Clyde M
authors.initials: CM
authors.lastname: Ofner
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004317:Doxorubicin; D005780:Gelatin