Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomy: A preclinical study

Opitz, Isabelle; Erne, Barbara; Demirbas, Seval; Jetter, Alexander; Seifert, Burkhardt; Stahel, Rolf A.; Weder, Walter

doi:10.1016/j.jtcvs.2010.09.032

Cited by 15 publications

(14 citation statements)

References 18 publications

(35 reference statements)

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“…This latter point is a significant point of differentiation of the cisplatin-loaded hyaluronate-based films with the approach using the fibrin sealant Vivostat ® proposed for the delivery of cisplatin intrapleurally. In fact, this latter approach has been reported to lead to very low blood levels of drug, indicating, similarly to what evidenced her for chitosan, a high interaction between the carrier and the anticancer drug (47). The hyaluronate film instead, is dissolving completely providing high cisplatin concentrations locally but allowing the complete release of the drug, its distribution and eventual anticancer action on secondary metastases and its disposal by renal elimination.…”

Section: Discussionmentioning

confidence: 69%

Physicochemical and pharmacokinetic properties of polymeric films loaded with cisplatin for the treatment of malignant pleural mesothelioma

Sonvico¹,

Barbieri²,

Colombo³

et al. 2018

J. Thorac. Dis.

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Background: Malignant mesothelioma is an invasive neoplasm arising from mesothelial surfaces of the pleural and peritoneal cavities. Mesothelioma treatment is unsatisfactory and recurrence is common. Here an innovative locoregional treatment for malignant pleural mesothelioma is presented. Methods: Chitosan-and hyaluronate-based films were loaded with 0.5% and 4% w/w cisplatin and were studied for their physicochemical, mechanical and drug release characteristics. The performance of the drug delivery systems was assessed in vitro on A549 cells and on an orthotopic model of MPM recurrence in rats. Results: Polysaccharide films produced were thin, flexible and resistant. Cisplatin was completely released from hyaluronic acid films within 96 hours, while drug release was found to be much more prolonged with chitosan films. The drug released from hyaluronate films was effective against A549 cell line, while for chitosan films the release was too slow to produce cytotoxicity. Similarly, cisplatin-loaded chitosan films in vivo released minimal quantities of cisplatin and induced inflammation and foreign body reaction. Cisplatinloaded hyaluronate acid films on the contrary were able to prevent tumor recurrence. The cisplatinloaded hyaluronate films provided higher C max and AUC compared to a solution of cisplatin administered intrapleurally, but did not show any sign of treatment related toxicity. Conclusions:Hyaluronate-based films appear as an optimal platform for the development of drug delivery systems suitable for the loco-regional post-surgical treatment of lung malignancies.

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Section: Discussionmentioning

confidence: 69%

Physicochemical and pharmacokinetic properties of polymeric films loaded with cisplatin for the treatment of malignant pleural mesothelioma

Sonvico¹,

Barbieri²,

Colombo³

et al. 2018

J. Thorac. Dis.

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“…Loco-regional therapy is certainly one of these targeted measures (6,9,14). Having that in mind, some years ago we focused efforts on polymeric films loaded with cisplatin (HYALCIS) which we applied intrapleurally in an orthotopic rat model of MPM (7).…”

Section: Discussionmentioning

confidence: 99%

“…Although the high levels of cisplatin registered, no significant toxicity related to the different treatments was observed (7). With this regard, the Swiss group coordinated by Prof. Weder, published several papers on the role of intrapleural chemotherapy with cisplatin loaded to the fibrin sealant Vivostat ® in the same rat mesothelioma model of tumor recurrence (6,9) and subsequently in pigs (14). The pleural and plasmatic platinum concentrations in the animals treated with the polymeric films were higher than those reported by the Swiss group.…”

Section: Introductionmentioning

confidence: 97%

“…Until now, the association of these different treatment modalities was able to lead only to a limited benefit in terms of overall survival and symptoms control (4,5). Recent progresses and increasing insight into the biologic features of MPM, including molecular and immunophenotypic characteristics, allowed testing a wide variety of combination chemotherapy and immunotherapy both in preclinical and clinical scenarios (6)(7)(8)(9). The interest of the international scientific community focused not only on treatment aspects but also on new diagnostic and prognostic biomarkers that could guide towards targeted therapies (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…The interest of the international scientific community focused not only on treatment aspects but also on new diagnostic and prognostic biomarkers that could guide towards targeted therapies (10)(11)(12). Locoregional treatment options, consisting in the intrapleural application of anti-tumor agents, have been used in the management of MPM (4)(5)(6)(7)(8)(9), usually within a multimodal approach (13). Some years ago, our group concentrated on an innovative drug formulation for the loco-regional treatment of MPM after surgery (7).…”

Section: Introductionmentioning

confidence: 99%

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Polymeric films loaded with cisplatin for malignant pleural mesothelioma: a pharmacokinetic study in an ovine model

et al. 2018

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Background: Malignant pleural mesothelioma (MPM) continues to be a distressing tumor due to its aggressive biologic behavior and scanty prognosis. Several therapeutic approaches have been tested both in clinical and preclinical settings, being intrapleural chemotherapy one of the most promising. Some years ago, our interest focused on polymeric films loaded with cisplatin for the adjuvant intrapleural treatment of surgical patients. After in vitro and in vivo studies in a rat recurrence model of MPM, the aim of this study Results: Twenty female Sardinian sheep with a mean weight of 45.1 kg were studied. All animals survived the surgical procedures. The whole surgical procedure had a mean duration of 113 minutes. Cisplatin blood levels obtained from polymeric films application were low during the first 24 hours after the application; then, the cisplatin blood level increased gradually and progressively until it reached significantly higher plasmatic concentrations after 120 hours compared to intrapleural cisplatin solution (P=0.004) and intravenous administration (P=0.001), respectively. Considering cisplatin concentration at 168 hours after the application, animals treated with polymeric films had higher plasmatic values than animals treated with intrapleural cisplatin solution and intravenous cisplatin (P=0.001). Despite the high cisplatin plasmatic concentrations, treatment related-toxicity towards kidneys and liver was comparatively lower compared to the intravenous and intrapleural cisplatin administration and closer to the control levels.

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Fibrin gels loaded with cisplatin and cisplatin-hyaluronate complexes tested in a subcutaneous human melanoma model

et al. 2015

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Fibrin gels are attractive biomaterials for local delivery of a variety of agents, from drugs to proteins. Similarly, polymer-anticancer-drug conjugates and nanoparticles are emerging as potential candidates for cancer treatment. Combining these different approaches, we have studied the efficacy of fibrin gels loaded with cisplatin (DDP) and a complex of DDP with hyaluronate (DDP-HA) for tumor growth inhibition in a melanoma model. Loaded gels prepared at relatively high fibrinogen concentration (22 mg/ml) showed good in vitro antiproliferative activities, prolonged release of the anticancer drug, and a long persistence (10-15 days) in vivo when implanted subcutaneously (sc) in immunodeficient mice. Gels loaded with DDP or DDP-HA containing 1/3 or even 1/6 of their systemic dose (6 mg/kg) and positioned under the tumor mass in mice bearing a sc human SK-Mel-28 tumor showed an antitumor activity better than that of the original parent compound given intraperitoneally (ip). Moreover, in an additional experiment in vivo, fibrin gels loaded with N-trimethyl chitosan-based nanoparticles containing a DDP-HA complex were assayed, resulting in a further 8 % improvement of anticancer activity, with lesser adverse systemic toxic effects. Taken together, these results suggest that the combination of fibrin gels and drugs complexed with suitable macromolecules holds great promise for loco-regional anticancer therapy of melanoma and other surgically removable cancer types.

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Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomy: A preclinical study

Cited by 15 publications

References 18 publications

Physicochemical and pharmacokinetic properties of polymeric films loaded with cisplatin for the treatment of malignant pleural mesothelioma

Physicochemical and pharmacokinetic properties of polymeric films loaded with cisplatin for the treatment of malignant pleural mesothelioma

Polymeric films loaded with cisplatin for malignant pleural mesothelioma: a pharmacokinetic study in an ovine model

Fibrin gels loaded with cisplatin and cisplatin-hyaluronate complexes tested in a subcutaneous human melanoma model

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