03351nas a2200421 4500008004100000022001400041245014900055210006900204260001300273300001200286490000700298520204300305653001902348653001202367653003202379653003602411653002602447653002202473653002702495653001402522653003002536653001602566653001702582653003602599653001902635653001302654653000902667653002202676653001702698653002202715100001802737700002502755700002402780700002002804700002602824700002002850856005902870 2005 eng d a1051-044300aCombined radiofrequency ablation and adjuvant liposomal chemotherapy: effect of chemotherapeutic agent, nanoparticle size, and circulation time.0 aCombined radiofrequency ablation and adjuvant liposomal chemothe c2005 Oct a1365-710 v163 a

PURPOSE: To evaluate the effects of liposomal chemotherapeutic agent, nanoparticle size, and liposome circulation time on tissue coagulation and intratumoral drug uptake when radiofrequency (RF) ablation is combined with adjuvant intravenous liposomal chemotherapy in an animal breast tumor model.

MATERIALS AND METHODS: Ninety-one R3230 mammary adenocarcinoma nodules were implanted in 48 Fischer rats. First, standardized RF ablation was combined with intravenous liposomal doxorubicin, cisplatin, or 5-fluorouracil (35 tumors each). Second, three different-sized doxorubicin-containing nanoparticle preparations were combined with standardized RF ablation. Last, two doxorubicin-containing liposome preparations with different blood elimination half-lives were combined with RF ablation. Coagulation diameter and interstitial doxorubicin concentration were measured 48 hours after treatment and compared with use of statistical analysis.

RESULTS: All combinations of RF with liposomal chemotherapy caused significantly greater tumor necrosis than RF alone (P<.05). Significantly increased necrosis was observed with intravenous liposomal RF/doxorubicin and RF/cisplatin compared with intravenous liposomal RF/5-fluorouracil (P<.01). Greater coagulation was observed with RF combined with 100-nm nanoparticles compared with 20-nm or 250-nm nanoparticles (P=.01 and P=.04, respectively). Additionally, greater intratumoral doxorubicin uptake was observed in the group treated with 20-nm nanoparticles compared with those treated with other sizes of nanoparticles (P<.05). RF plus liposomal doxorubicin produced greater coagulation and intratumoral doxorubicin uptake than RF plus 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid (P<.05).

CONCLUSION: When combined with RF ablation, modification of adjuvant intravenous liposomal chemotherapy, including nanoparticle size, circulation time, and chemotherapeutic agent, can influence intratumoral drug accumulation and tissue coagulation.

10aAdenocarcinoma10aAnimals10aAntibiotics, Antineoplastic10aAntimetabolites, Antineoplastic10aAntineoplastic Agents10aCatheter Ablation10aChemotherapy, Adjuvant10aCisplatin10aCombined Modality Therapy10aDoxorubicin10aFluorouracil10aMammary Neoplasms, Experimental10aNanostructures10aNecrosis10aRats10aRats, Inbred F34410aTime Factors10aTreatment Outcome1 aAhmed, Muneeb1 aLukyanov, Anatoly, N1 aTorchilin, Vladimir1 aTournier, Herve1 aSchneider, Anatoly, N1 aGoldberg, Nahum uhttps://www.microfluidicsciences.com/drupal/?q=node/14