PMID- 12550786
OWN - NLM
STAT- MEDLINE
DCOM- 20030815
LR  - 20190910
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 252
IP  - 1-2
DP  - 2003 Feb 18
TI  - Stabilization of recombinant interferon-alpha by pegylation for encapsulation in 
      PLGA microspheres.
PG  - 111-22
AB  - Interferon-alpha (IFN) was pegylated and encapsulated in biodegradable 
      microspheres to achieve a long-acting formulation. IFN was pegylated with 
      methoxy-polyethylene glycol (mPEG, MW 2000 or 5000). The conjugation procedures 
      were optimized in terms of concentration of the reactants and the pH condition of 
      the medium. The conjugates (IFN-mPEG(2000) and IFN-mPEG(5000)) were characterized 
      using SDS-PAGE, size-exclusion-HPLC (SE-HPLC) and matrix-assisted laser 
      desorption and ionization time-of-flight (MALDI-TOF) mass spectroscopy. The 
      optimized IFN-mPEG conjugates consisted of mono- and multi-pegylated derivatives 
      along with a small amount of native IFN (</=5%). In the simulation studies for 
      microencapsulation, pegylated IFN showed better stability when exposed to 
      dichloromethane as compared to native IFN. In vitro release profiles of IFN and 
      IFN-mPEG from biodegradable poly(D,L-lactide-co-glycolide) microspheres were 
      quite different. Native IFN was released only 16.3+/-0.4% after 3 weeks, but 
      IFN-mPEG(2000) and IFN-mPEG(5000) were released 72.5+/-2.1 and 56.8+/-2.5%, 
      respectively after the same period. It was found that in contrast to native IFN, 
      the pegylated IFN was able to largely retain its native aqueous solubility after 
      being exposed to detrimental conditions of microencapsulation, resulting in a 
      continuous release in vitro. These studies show the possibility of preparation of 
      a long-acting dosage form for IFN using a combination of pegylation and 
      microencapsulation techniques.
FAU - Diwan, Manish
AU  - Diwan M
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, 305-701, Daejeon, South Korea.
FAU - Park, Tae Gwan
AU  - Park TG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Interferon Type I)
RN  - 0 (Polymers)
RN  - 0 (Recombinant Proteins)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Drug Compounding
MH  - Drug Stability
MH  - Interferon Type I/analysis/*chemistry
MH  - Lactic Acid/analysis/*chemistry
MH  - Microspheres
MH  - Polyglycolic Acid/analysis/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Polymers/analysis/*chemistry
MH  - Recombinant Proteins
EDAT- 2003/01/29 04:00
MHDA- 2003/08/16 05:00
CRDT- 2003/01/29 04:00
PHST- 2003/01/29 04:00 [pubmed]
PHST- 2003/08/16 05:00 [medline]
PHST- 2003/01/29 04:00 [entrez]
AID - S0378517302006361 [pii]
AID - 10.1016/s0378-5173(02)00636-1 [doi]
PST - ppublish
SO  - Int J Pharm. 2003 Feb 18;252(1-2):111-22. doi: 10.1016/s0378-5173(02)00636-1.