title: Monitoring the in vivo delivery of proteins from carbomer hydrogels by X-ray fluorescence.
abstract: OBJECTIVE
  To measure the effect of protein size on their disappearance from subcutaneously implanted carbomer hydrogel matrices.
  
  
  METHODS
  A series of different molecular weight (MW) proteins were iodinated, incorporated into Carbopol hydrogels, injected subcutaneously into rats, and monitored using X-ray fluorescence (XRF).
  
  
  RESULTS
  A 10 mg/mL minimum concentration of Carbopol-940 was necessary before protein 150 mg/mL iodinated bovine serum albumin (I-BSA)] retention times increased with increasing hydrogel concentration. The decreasing protein signal was not caused by outward protein diffusion or iodoprotein hydrolysis. As the protein MW increased, protein retention times lengthened [e.g.. 6.2 h for insulin (5.7 kDa) to 13.3 h for thyroglobulin (669 kDa)]. Protein disappearance was monophasic first-order for some proteins and biphasic first-order for others. The disappearance rate constant ranged from 0.093 +/- 0.005 h(-1/2), to 0.187 +/- 0.057 h(-1/2), indicating gel erosion rather than protein diffusion as the rate-limiting mechanism. Entrapped I-BSA in Carbopol-1342 NF. pH 7.4, and Carbopol 2001-ETD, pH 7.4, gel matrices yielded different disappearance rates and profiles than Carbopol-940. The overall 50% disappearance rate of I-BSA was greatest for Carbopol-1342 NF (41 +/- 8 h), followed by Carbopol-2001 ETD (25 +/- 2 h) and Carbopol-940 (10.5 +/- 0.7 h).
  
  
  CONCLUSIONS
  XRF is a noninvasive technique that can be used to follow the status of macromolecules in vivo.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence. Kansas 66047, USA. dmaclean@ku.edu
authors.forename: Donald S
authors.initials: DS
authors.lastname: MacLean-McDavitt
authors.forename: J David
authors.initials: JD
authors.lastname: Robertson
authors.forename: Michael
authors.initials: M
authors.lastname: Jay
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D005260:Female; D020100:Hydrogels / Q000737:chemistry*; D007279:Injections, Subcutaneous; D008954:Models, Biological; D010316:Particle Size; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D013997:Time Factors
chemical_list: D000180:Acrylic Resins; D020100:Hydrogels; D011506:Proteins; C006903:carbopol 940