PMID- 11400139
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20190910
IS  - 0021-9304 (Print)
IS  - 0021-9304 (Linking)
VI  - 56
IP  - 4
DP  - 2001 Sep 15
TI  - A comparative biocompatibility study of microspheres based on crosslinked dextran 
      or poly(lactic-co-glycolic)acid after subcutaneous injection in rats.
PG  - 600-9
AB  - Microspheres based on methacrylated dextran (dex-MA), dextran derivatized with 
      lactate-hydroxyethyl methacrylate (dex-lactate-HEMA) or derivatized with HEMA 
      (dex-HEMA) were prepared. The microspheres were injected subcutaneously in rats 
      and the effect of the particle size and network characteristics [initial water 
      content and degree of methacrylate substitution (DS)] on the tissue reaction was 
      investigated for 6 weeks. As a control, poly(lactic-co-glycolic)acid (PLGA) 
      microspheres with varying sizes (unsized, smaller than 10 microm, smaller and 
      larger than 20 microm) were injected as well. A mild tissue reaction to the PLGA 
      microspheres was observed, characterized by infiltration of macrophages (MOs) and 
      some granulocytes. Six weeks postinjection, the PLGA microspheres were still 
      present. However, their size was decreased indicating degradation and many 
      spheres had been phagocytosed. The tissue reaction was hardly affected by size 
      differences, except for particles smaller than 10 microm, which induced an 
      extensive tissue reaction. The initial tissue reaction to nondegradable dex-MA 
      microspheres was stronger than towards the PLGA microspheres, but at day 10 the 
      tissue reactions were comparable for both groups. Six weeks postinjection, the 
      dex-MA microspheres were completely phagocytosed, and no signs of degradation 
      were observed. The size and initial water content of dex-MA microspheres hardly 
      affected the tissue response, although less granulocytes were observed for 
      microspheres with higher DS. Slowly degrading dextran microspheres composed of 
      dex-(lactate(1)-)HEMA induced a tissue reaction comparable to the PLGA 
      microspheres. However, degradation of the dex-(lactate(1,3)-)HEMA microspheres 
      was associated with an increased number of MO's and giant cells, both 
      phagocytosing the microspheres and their degradation products. Similar to PLGA, 
      no adverse reactions were observed for the nondegradable dex-MA and degradable 
      dextran microspheres. This study shows that both nondegradable and degradable 
      dextran-based microspheres are well tolerated after subcutaneous injection in 
      rats, which make them interesting candidates as controlled drug delivery systems.
CI  - Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 56: 600--609, 2001
FAU - Cadee, J A
AU  - Cadee JA
AD  - Faculty of Pharmacy, Department of Pharmaceutics, Utrecht Institute for 
      Pharmaceutical Sciences, P.O. Box 80 082, 3508 TB Utrecht, The Netherlands.
FAU - Brouwer, L A
AU  - Brouwer LA
FAU - den Otter, W
AU  - den Otter W
FAU - Hennink, W E
AU  - Hennink WE
FAU - van Luyn, M J
AU  - van Luyn MJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biomed Mater Res
JT  - Journal of biomedical materials research
JID - 0112726
RN  - 0 (Biocompatible Materials)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Dextrans)
RN  - 0 (Drug Carriers)
RN  - 0 (Polymers)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Animals
MH  - *Biocompatible Materials
MH  - Cross-Linking Reagents
MH  - Dextrans
MH  - *Drug Carriers
MH  - *Lactic Acid
MH  - Microspheres
MH  - *Polyglycolic Acid
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - *Polymers
MH  - Rats
EDAT- 2001/06/16 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/06/16 10:00
PHST- 2001/06/16 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/06/16 10:00 [entrez]
AID - 10.1002/1097-4636(20010915)56:4<600::AID-JBM1133>3.0.CO;2-I [pii]
AID - 10.1002/1097-4636(20010915)56:4<600::aid-jbm1133>3.0.co;2-i [doi]
PST - ppublish
SO  - J Biomed Mater Res. 2001 Sep 15;56(4):600-9. doi: 
      10.1002/1097-4636(20010915)56:4<600::aid-jbm1133>3.0.co;2-i.