PMID- 17938009
OWN - NLM
STAT- MEDLINE
DCOM- 20080228
LR  - 20131121
IS  - 1742-7061 (Print)
IS  - 1742-7061 (Linking)
VI  - 4
IP  - 1
DP  - 2008 Jan
TI  - Effect of macromer molecular weight on in vitro ophthalmic drug release from 
      photo-crosslinked matrices.
PG  - 1-10
AB  - The objective of this study was to investigate the effect of poly(propylene 
      fumarate) (PPF) molecular weight on the release kinetics of two ophthalmic model 
      drugs, acetazolamide (AZ) and timolol maleate (TM), from matrices prepared by 
      photo-induced copolymerization of PPF with N-vinyl pyrrolidone (NVP). PPF 
      macromers of different number average molecular weight (M(n)) and polydispersity 
      index (PI) were used in the experiments. Photo-crosslinked matrices were loaded 
      with 5wt.% AZ or TM. The amounts of released drug and NVP were determined using 
      high-performance liquid chromatography (HPLC). The release kinetics of both drugs 
      was influenced by the molecular weight of the constituent PPF macromer. An 
      increased M(n) led to an increased burst release and an accelerated drug release. 
      Dependent on the PPF M(n), the initial AZ loading was released within periods 
      ranging from 35 days (M(n) = 3670, PI = 1.9) to 220 days (M(n) = 2050, PI=1.5). 
      TM-loaded matrices revealed similar release kinetics dependent on the PPF M(n). 
      The amount of released NVP from photo-crosslinked matrices during the course of a 
      release experiment was independent of the PPF M(n) for both drugs. Matrix 
      swelling and erosion were determined gravimetrically. The network structures of 
      non-loaded matrices were further characterized by determining their crosslinking 
      densities and the relative double bond conversions of fumaric acid (FAA) and NVP. 
      Independent of PPF M(n), PPF and NVP similarly participated in the formation of 
      the PPF/polyNVP copolymer network. The observed differences in drug release might 
      therefore be explained by differences in the microstructural organization of the 
      copolymer networks. Overall, the results demonstrate that drug release kinetics 
      from photo-crosslinked PPF/polyNVP matrices is strongly dependent on the M(n) of 
      the PPF macromer.
FAU - Haesslein, A
AU  - Haesslein A
AD  - Department of Bioengineering, Rice University, Houston, TX 77251-1892, USA.
FAU - Hacker, M C
AU  - Hacker MC
FAU - Mikos, A G
AU  - Mikos AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070911
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Biocompatible Materials)
RN  - 0 (Drug Carriers)
RN  - 0 (Fumarates)
RN  - 0 (Polypropylenes)
RN  - 0 (Pyrrolidinones)
RN  - 0 (poly(propylene fumarate))
RN  - 76H9G81541 (N-vinyl-2-pyrrolidinone)
RN  - 817W3C6175 (Timolol)
RN  - O3FX965V0I (Acetazolamide)
SB  - IM
MH  - Acetazolamide/*administration & dosage
MH  - Biocompatible Materials/*chemistry
MH  - Drug Carriers/*chemistry
MH  - Fumarates/*chemistry/radiation effects
MH  - Kinetics
MH  - Molecular Weight
MH  - Photochemistry
MH  - Polypropylenes/*chemistry/radiation effects
MH  - Pyrrolidinones/chemistry/metabolism
MH  - Timolol/*administration & dosage
EDAT- 2007/10/17 09:00
MHDA- 2008/02/29 09:00
CRDT- 2007/10/17 09:00
PHST- 2007/07/13 00:00 [received]
PHST- 2007/08/17 00:00 [revised]
PHST- 2007/08/27 00:00 [accepted]
PHST- 2007/10/17 09:00 [pubmed]
PHST- 2008/02/29 09:00 [medline]
PHST- 2007/10/17 09:00 [entrez]
AID - S1742-7061(07)00144-4 [pii]
AID - 10.1016/j.actbio.2007.08.011 [doi]
PST - ppublish
SO  - Acta Biomater. 2008 Jan;4(1):1-10. doi: 10.1016/j.actbio.2007.08.011. Epub 2007 
      Sep 11.