(1) Both types of microsphere overcame the initial rapid release of cDDP (burst effect), and PLAGA-coated albumin microspheres also showed a lag phase of approximately 30 min before cDDP release began.
(2) PLAGA-coated albumin microspheres released most of their payload through diffusion, and the coating eventually cracked after 7 days' incubation in saline supplemented with 0.1% Tween at 37 degrees C, enabling the release of any cDDP remaining.
(3) Effects of platinum, pre-released from PLAGA-coated albumin microspheres on the in vitro growth of L1210 cells were comparable with those of standard formulations (dissolved) of cDDP.
(4) Liver-to-kidney platinum level ratios were 28 times higher after 4 h and 19 times higher after 24 h with PLAGA-cDDP microspheres than with free cDDP.
(5) Protein-linked 1-hydroxyethylphosphonate was previously described as the dead-end product after reaction of the analogue with the intermediary acetyl-enzyme form of the catalytic cycle [W. Plaga et al.
(6) PLAGA-cDDP microspheres may, therefore, be a useful and effective addition to current techniques of loco-regional chemotherapy for disseminated hepatic tumors.
(7) These findings indicate a sparing effect on normal tissues when cDDP is targeted to the liver by formulation in PLAGA.
(8) These studies show that formulation of cDDP in PLAGA-based microspheres prevents the rapid burst effect of cDDP seen in previous preparations and offers an improved system of administration for hepatic artery infusion or adjuvant therapy, enabling better clinical handling and the promise of a higher ratio of tumour tissue to normal tissue.
(9) We used a poly-lactide-co-glycolide polymer (PLAGA 50:50) to formulate cisplatin (cDDP) into microspheres designed for intravascular administration.
(10) In a CC531 colon carcinoma liver micrometastases model, cytotoxicity of microsphere-released cDDP was confirmed in vivo by equal inhibition of tumor growth by PLAGA-cDDP and free cDDP over a period of 26 days.
(11) Kidney platinum levels were 7 times lower when PLAGA-cDDP was used.
(12) PLAGA-coated albumin microspheres and microspheres consisting of PLAGA only.
(13) Material released from non-drug-loaded PLAGA microspheres had no effect on L1210 cell growth, suggesting the absence of cytotoxic compounds in the matrix.
(14) Liver-to-blood platinum ratios at these times were 38 times and 36 times higher using PLAGA-cDDP.
Plagate
Definition:
(a.) Having plagae, or irregular enlongated color spots.