Intra-articular treatment of arthritis with microsphere formulations of paclitaxel: biocompatibility and efficacy determinations in rabbits.
OBJECTIVE
To assess the biocompatibility of controlled release microspheres prepared from different polymeric biomaterials in various size ranges in rabbit synovial joints and based on these data, design and evaluate the efficacy of an intra-articular, paclitaxel-loaded microspheres formulation in rabbit models of arthritis.


METHODS
Paclitaxel-loaded microspheres of poly(lactide-co-glycolide) (PLGA), poly(L-lactic acid) (PLA) and poly(caprolactone) (PCL) were prepared in different size ranges and inflammatory responses monitored following injection into healthy rabbit joints. The efficacy of 20% paclitaxel-loaded PLA microspheres (35-105 microm size range) injected intra-articularly into antigen and carrageenan induced rabbit models of arthritis was monitored.


RESULTS
Polymeric microspheres in the 35-105 microm size range were biocompatible whereas smaller microspheres (1-20 microm) produced an inflammatory response. Efficacy studies showed that injection of 20% paclitaxel-loaded PLA microspheres significantly reduced all measures of inflammation in the antigen arthritis rabbit model.


CONCLUSIONS
Paclitaxel-loaded PLA microspheres in the 35-105 microm size range, released paclitaxel in a controlled manner over several weeks, and may be a potential formulation for the intra-articular treatment of inflammation in arthritic conditions.
Liggins
R T
RT
Angiotech Pharmaceuticals Inc., Vancouver, British Columbia, Canada.
Cruz
T
T
Min
W
W
Liang
L
L
Hunter
W L
WL
Burt
H M
HM
D000818:Animals; D001168:Arthritis / Q000150:complications / Q000188:drug therapy*; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D048271:Chitosan / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D007270:Injections, Intra-Articular; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008422:Materials Testing; D008863:Microspheres; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013582:Synovial Fluid; D016896:Treatment Outcome
D001672:Biocompatible Materials; D048271:Chitosan; D017239:Paclitaxel