Tumor retention and biodistribution studies of etoposide loaded tripalmitin nanoparticles after intratumoral administration in Dalton's Iymphoma tumor bearing mice

The objective of the present work is to study the biodistribution and tumor retention properties of etoposide (anticancer agent) and etoposide loaded tripalmitin nanoparticles (ETPL) after intratumoral administration in Dalton's lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by spray drying technique. The nanoparticles were uniform and possessed 387 nm mean diameter and negative charge with excellent redispersibility in aqueous media. Radiolabeling of etoposide and ETPL nanoparticles with Technetium-99m (99mTc) resulted in complexes with high labeling efficiency and low radiocolloid formation. The labeled complexes showed good in vitro stability as indicated by low transchelation in presence of DTPA and cysteine and stability in human serum. Biodistribution and tumor retention studies were performed for etoposide and ETPL nanoparticles after intratumoral injection in mice bearing Dalton's lymphoma tumor. Etoposide experienced rapid clearance from the tumor, while the disposition of ETPL nanoparticles was slower. The tissue concentrations of ETPL nanoparticles increased with time (i.e. at 6h and 24h post injection) indicating its retention in tumor site for a longer time. Tumor retention of both etoposide and ETPL nanoparticles was studied upto 48h post injection. The tumor concentration of both etoposide and ETPL nanoparticles was high initially (8.57 percent and 41.8 percent injected dose at 0.5h post injection) and decreased with time (0.12 percent and 1.68 percent injected dose at 48h post injection). The concentration of etoposide rapidly declined from the tumor site while the tumor retention of ETPL nanoparticles was significantly higher than free etoposide (P < 0.001) at all the time points studied. The over all many fold higher tumor retention of ETPL nanoparticles (14 folds even at 48h post injection) compared to etoposide, coupled with lower tissue distribution signifies...

Tratamento sistêmico do sarcoma de Kaposi associado a AIDS: estudo clínico e farmacológico com doses fracionadas de etoposida por via oral / Treatment of AIDS related Kaposiïs sarcoma: clinical and pharmacological study with oral etoposide

Os objetivos deste estudo foram: avaliar a atividade antitumoral, a toxicidade e a farmacocinética da etoposida em doses orais fracionadas por um período de tempo prolongado em pacientes com Sarcoma de Kaposi avançado associado a AIDS; determinar o percentual de respostas objetivas alcançado pela etoposida na posologia proposta no estudo; estabelecer o perfil e a gravidade dos efeitos tóxicos apresentados pelos pacientes nesse esquema de administração da etoposida e descrever a farmacocinética da etoposida no plasma dos pacientes incluidos no estudo

Bioavailability of etoposide after oral administration of the solution marketed for intravenous use: Therapeutic and pharmacoeconomic perspectives

Background. Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES). Methods. Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and biovailability parameters were calculated. Results. Oral IVES yielded an adequate bioavailability profile because Cmax was 2.38 ñ 0.30 µg/mL, AUC was 12.87 ñ 2.02 µg/mL and half-life was 6.72 ñ 0.97 h. Conclusions. Considering that the pharmacokinetic aim is to maintain plasm concentrations between 0.5 and 1.0 µg/mL for several hours while avioding high concentrations, i.e., of 10 µg/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration