Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platinum-based polymeric nano-drugs, especially cisplatin-loaded polymeric nanoparticles (CDDP-NPs), have been extensively exploited for the treatment of solid tumors. However, it is still unclear what role the processing procedure and the properties of the polymeric carrier materials may play in influencing the plasma pharmacokinetics, biodistribution and in vivo efficacy of CDDP-NPs. In this study, a series of poly(l-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-mPEG) copolymers were synthesized for the preparation of CDDP-loaded PLG-g-mPEG (CDDP/PLG-g-mPEG) nanoparticles. All of the parameters, including PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length, ultrafiltration purification and cisplatin loading content, were found to have a significant influence on the plasma pharmacokinetics of the CDDP/PLG-g-mPEG nanoparticles. The blood circulation time of the nanoparticles was prolonged with increases in PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length and CDDP loading content. The use of ultrafiltration purification could prolong the blood circulation time of the nanoparticles as well. Experiments to measure the pharmacokinetics and biodistribution demonstrated that the selected CDDP/PLG-g-mPEG nanoparticles, NP10, had a long blood circulation time and could achieve selective and significant accumulation in Lewis lung carcinoma (LLC) tumors. The platinum plasma concentrations in the LLC tumor-bearing mice receiving NP10 remained up to 46-fold higher than that of mice receiving equivalent doses of free CDDP. In addition, the plasma area under the concentration time curve (AUC) of NP10 was 31-fold higher than that of free CDDP in 48h. The platinum concentration ratio of NP10 to free CDDP in tumors reached as high as 9.4. The tumor AUC ratio of NP10 to CDDP was 6. Using a mouse C26 tumor model, here we demonstrate that NP10 improves the safety and tolerance in vivo when compared to CDDP and effectively inhibits the growth of C26 tumors. Furthermore, increasing the dosage of NP10 by 2 or 3-fold of free CCDP improved its anticancer efficacy to comparable or higher levels. These results indicate that CDDP/PLG-g-mPEG nanoparticles have greater potential for the treatment of solid tumors in clinical application.
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PMID:Pharmacokinetics, biodistribution and in vivo efficacy of cisplatin loaded poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) complex nanoparticles for tumor therapy. 2552 33

Cisplatin-loaded poly(l-glutamic acid)-g-methoxy poly(ethylene glycol 5K) nanoparticles (CDDP-NPs) were characterized and exploited for the treatment of non-small cell lung carcinoma (NSCLC). In vitro metabolism experiments showed that a glutamic acid 5-mPEG ester [CH3O(CH2CH2O)nGlu] was generated when the poly(l-glutamic acid)-g-methoxy poly(ethylene glycol 5K) (PLG-g-mPEG5K) was incubated with HeLa cells. This suggests that the poly(glutamic acid) backbone of the PLG-g-mPEG5K is biodegradable. Furthermore, the size of the CDDP-NPs in an aqueous solution was affected by varying the pH (5.0-8.0) and their degradation rate was dependent on temperature. The CDDP-NPs could also bind to the model nucleotide 2'-deoxyguanosine 5'-monophosphate, indicating a biological activity similar to cisplatin. The CDDP-NPs showed a significantly lower peak renal platinum concentration after a single systemic administration when compared to free cisplatin. In vivo experiments with a Lewis lung carcinoma (LLC) model showed that the CDDP-NPs suppressed the growth of tumors. In addition, LLC tumor-bearing mice treated with the CDDP-NPs (5mg/kg cisplatin eq.) showed much longer survival rates (median survival time: 51days) as compared with mice treated with free cisplatin (median survival time: 18days), due to the acceptable antitumor efficacy and low systemic toxicity of CDDP-NPs. These results suggest that the CDDP-NPs may be successfully applied to the treatment of NSCLC.
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PMID:Cisplatin-loaded polymeric nanoparticles: characterization and potential exploitation for the treatment of non-small cell lung carcinoma. 2570 22