PMID- 9269868
OWN - NLM
STAT- MEDLINE
DCOM- 19970925
LR  - 20181130
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 86
IP  - 8
DP  - 1997 Aug
TI  - Factors affecting the in vitro release of recombinant human interferon-gamma 
      (rhIFN-gamma) from PLGA microspheres.
PG  - 908-14
AB  - A long-acting depot formulation of recombinant human interferon-gamma 
      (rhIFN-gamma) was achieved by microencapsulation of rhIFN-gamma in 
      polylactic-coglycolic acid (PLGA) microspheres by a water-in-oil-in-water 
      technique. The release of protein was assessed with different release devices and 
      buffer systems. The quality of the released protein was quantitated by sodium 
      dodecyl sulfate-size exclusion chromatography, ELISA, and bioactivity assays. The 
      microencapsulation process resulted in an encapsulation efficiency of 100% and 
      the initial release of bioactive, native protein with no subsequent release. 
      Further investigation suggested that the protein did not bind to the PLGA, but a 
      constant and small amount of protein adsorbed to the filter device used for the 
      release studies. The composition of the release media (pH, buffer species, salt 
      concentration, ionic strength, and type and concentration of surfactants) had a 
      profound effect on the in vitro release rate. The effect was mainly due to the 
      differential solubility, stability, and aggregation of rhIFN-gamma in the various 
      systems for protein inside the microspheres or released into the bulk solution. 
      The quality of the protein released from the microspheres was also affected by 
      the buffer media upon storage at 5 degrees C, which, in turn, affected the 
      quantification of released protein. The bicinchoninic acid method typically used 
      to quantitate protein release underestimated protein release because of 
      aggregation. Protein released after several days was less active than the 
      starting material and had lost activity as a result of the inherent instability 
      of rhIFN-gamma at 37 degrees C. The release device, buffer species, pH, and 
      excipients must be assessed in release studies of proteins from polymer matrices 
      because the protein stability and release is dependent on these variables. These 
      studies also indicated that rhIFN-gamma was encapsulated and released from PLGA 
      in a bioactive form, but its stability at 37 degrees C, which was greatly 
      affected by the release conditions, limits the duration of release of native, 
      bioactive protein to 7 days or less.
FAU - Yang, J
AU  - Yang J
AD  - Pharmaceutical R & D, Genentech, Inc., S. San Francisco, CA 94080, USA.
FAU - Cleland, J L
AU  - Cleland JL
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Drug Carriers)
RN  - 0 (Polymers)
RN  - 0 (Recombinant Proteins)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Chromatography, Gel
MH  - Drug Carriers
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Interferon-gamma/administration & dosage/*pharmacokinetics
MH  - Lactic Acid
MH  - Microspheres
MH  - Polyglycolic Acid
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Polymers
MH  - Recombinant Proteins/administration & dosage/pharmacokinetics
MH  - Tumor Cells, Cultured
EDAT- 1997/08/01 00:00
MHDA- 2000/07/19 11:00
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 2000/07/19 11:00 [medline]
PHST- 1997/08/01 00:00 [entrez]
AID - S0022-3549(15)50357-2 [pii]
AID - 10.1021/js960480l [doi]
PST - ppublish
SO  - J Pharm Sci. 1997 Aug;86(8):908-14. doi: 10.1021/js960480l.