Poly camptothecin

Shenderova, A., Burke, T. G., and Schwendeman, S. P. (1999), The acidic microclimate in poly(lactide-co-glycolide) microspheres stabilizes camptothecins, Pharm. Res., 16, 241-248. 

Bhatt [3] prepared antineoplastic agents consisting of poly-L-glutamic acid— camptothecin conjugates, (III) and (IV), as a method for improving the limited solubility of 20(S)-camptothecin and analogues in aqueous medium. 

Poly(glutamic acid) Camptothecin Ester Mice bearing human lung H3222 l... 

Zhang, L. Hu, Y Jiang, X. Yang, C. Lu, W. Yang, Y. H. Camptothecin derivative-loaded poly(caprolactone-co-lactide)-b-REG-b-poly(caprolactone-co-lactide) nanoparticles and their biodistribution in mice. J. Control. Release 2004, 96, 135-148. 

Miura, H. Onishi, H. Sasatsu, M. Machida, Y. Antitumor characteristics of methoxypoly-ethylene glycol-poly(dl-lactic acid) nanoparticles containing camptothecin. J. Control. Release 2004, 97, 101-113. 

Zamai, M., vandeVen, M., Farao, M., Gratton, E., Ghiglieri, A., Castelli, M. G., Fontana, E., d Argy, R., Fiorino, A., Pesenti, E., Suarato, A., Caiolfa, V. R. Camptothecin poly[7V-(2-hydroxypropyl) methacrylamide] copolymers in antitopoisomerase-1 tumor therapy intratumor release and antitumor efficacy. Mol. Cancer Then 2003, 2, 29—40. 

Aniineoplasitc agents, Chinese plant-derived camptothecin derivatives, SI cotchicine derivatives, 34 description of, SO flavomiid derivatives, Sl-84 poly enolic compounds, 81 quassinoids, 81 quirtone derivatives. 84-86 sesquiterpene lactones, 81 Antioxjdanis... 

Ertl B, Platzer P, Wirth M, Gabor F. Poly(D,L-lactic-co-glycolic acid) microspheres for sustained delivery and stabilization of camptothecin. Journal of Controlled Release. September 20, 1999 61(3) 305— 317. PubMed PMID 10477803. 

More recently, camptothecin (CPT) was conjugated to poly(l-hydroxymethylethylene hydroxymethylformyl) (PHF or Eleximer ) and the conjugate 11 (XMT-1001) is currently in clinical development [72,73]. The polyacetal is derived from the exhaustive oxidation of dextran [74]. CPT is poorly soluble and prone to rapid inactivation through lactone ring hydrolysis in vivo [75]. As a cytotoxic compound, CPT has been used in many efforts to develop other CPT-polymer conjugates [45,76,77]. The sodium salt of CPT has also been examined in phase I trials, but only modest responses were observed while severe toxicities remain. 

J. Singer, R. Bhatt, J. Tulinsky, K. Buhler, E. Heasley, P. Klein, P. de Vries, Water-soluble poly-(L-glutamic add)-gly-camptothecin conjugates enhance camptothecin stability and efficacy in vivo, J. Control. Release 74 (2001) 243-247. 

R.B. Kolhatkar, P. Swaan, H. Ghandehari, Potential oral delivery of 7-ethyl-lO-hydroxy-camptothecin (SN-38) using poly (amido-amine) dendrimers, Pharm. Res. 25 (7) (2008) 1723-1729. 

The mechanism underlying the potentiation ofTopo I poisons by PARP inhibitors has not been fully elucidated, but could be a function ofTopo I activity or DNA repair. PARP-1 poly(ADP-ribosylates) Topo I, down-r ulating its activity in vitro and in intact cells and inhibition of PARP may therefore increase Topo I activity and hence sensitivity to Topo I poisons. Mattern et al su sted that sensitisation to camptothecin they observed with 3AB was due to de-repression of topoisomerase activity rather than a direct effect of PARP inhibition on DNA repair. " Consistent with this hypothesis is the observation that Topo I was activated 800% association with PARP-1 but poly(ADP-ribosylation) ofTopo I or its association with automodified PARP-1 inhibited Topo I activity, which could be restored in the presence of 1 mM benzamide. These studies demonstrated that association with unmodified PARP enhanced Topo I DNA binding and strand scission, but that poly(ADP-ribosylated) PARP probably repels Topo I from the DNA. 

Camptothecin Poly(laotlo-oo-glyoollo aold Antineoplastio... 

Poly(ethylene glycol) (PEG) is a nondegradable synthetic polymer that has been extensively studied as a polymer-drug carrier. PEG is hydrophilic and is well tolerated in human. The main disadvantage of PEG is that the polymer backbone is not biodegradable in vivo. PEG has been used to conjugate anticancer drugs such as doxorubicin [311], camptothecin... 

Apart from these properties, the release kinetics can be manipulated in such a way that drug release occurs due to a trigger from an environmental stimulus like pH, temperature, etc. [88]. The thermoresponsive graft co-polymeric 5-FU-loaded nanoparticles made from chitosan-g-poly(A -vinylcaprolactam), prepared by an ionic crosslinking method, showed a lower critical solution temperature (LCST) at 38 C, with a prominent in vitro drug release above LCST [89]. Camptothecin-loaded polyfiV-isopropylacrylamide) (PNIPAAm)/chitosan nanoparticles were... 

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