PMID- 12387951
OWN - NLM
STAT- MEDLINE
DCOM- 20030422
LR  - 20190916
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 83
IP  - 3
DP  - 2002 Oct 30
TI  - Double-walled microspheres for the sustained release of a highly water soluble 
      drug: characterization and irradiation studies.
PG  - 437-52
AB  - Composite double-walled microspheres with biodegradable poly(L-lactic acid) 
      (PLLA) shells and poly(D,L-lactic-co-glycolic acid) (PLGA) cores were fabricated 
      with highly water-soluble etanidazole entrapped within the core as solid 
      crystals. This paper discusses the characterization, in vitro release and the 
      effects of irradiation on this class of microsphere. Through the variation of 
      polymer mass ratios, predictable shell and core dimensions could be fabricated 
      and used to regulate the release rates. A direct and simple method was devised to 
      determine the composition of the shell and core polymer based on the different 
      solubilities of the polymer pair in ethyl acetate. A distribution theory based on 
      solubility parameter explains why highly hydrophilic etanidazole has the tendency 
      to be distributed consistently to the more hydrophilic polymer. Release profiles 
      for normal double-walled samples have about 80% of drug released over 10 days 
      after the initial time lag, while for irradiated double-walled samples, the 
      sustained release lasted for more than 3 weeks. Although sustained release was 
      short of the desired 6-8 weeks required for therapy, a low initial burst of less 
      than 5% and time lags that can be manipulated, allows for administration of these 
      microspheres together with traditional ones to generate pulsatile or new type of 
      releases. The effects of irradiation were also investigated to determine the 
      suitability of these double-walled microspheres as delivery devices to be used in 
      conjunction with radiotherapy. Typical therapeutic dosage of 50 Gy was found to 
      be too mild to have noticeable effects on the polymer and its release profiles, 
      while, sterilization dosages of 25 kGy, lowered the glass transition temperatures 
      and crystalline melting point, indirectly indicating a decrease in molecular 
      weight. This accelerated degradation of the polymer, hence releasing the drug.
FAU - Lee, Teng Huar
AU  - Lee TH
AD  - Department of Chemical and Environmental Engineering, National University of 
      Singapore, 4 Engineering Drive 4, Singapore.
FAU - Wang, Jianjun
AU  - Wang J
FAU - Wang, Chi-Hwa
AU  - Wang CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Delayed-Action Preparations)
RN  - 059QF0KO0R (Water)
SB  - IM
MH  - Delayed-Action Preparations/*chemical synthesis/*pharmacokinetics
MH  - *Gamma Rays
MH  - Microspheres
MH  - Solubility
MH  - Water/*chemistry/metabolism
EDAT- 2002/10/22 04:00
MHDA- 2003/04/23 05:00
CRDT- 2002/10/22 04:00
PHST- 2002/10/22 04:00 [pubmed]
PHST- 2003/04/23 05:00 [medline]
PHST- 2002/10/22 04:00 [entrez]
AID - S0168365902002353 [pii]
AID - 10.1016/s0168-3659(02)00235-3 [doi]
PST - ppublish
SO  - J Control Release. 2002 Oct 30;83(3):437-52. doi: 10.1016/s0168-3659(02)00235-3.