Abstract:Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of ovarian cancer, but the full potential is yet to be realized. To facilitate IP chemotherapy of ovarian cancer, we developed an in-situ crosslinkable hydrogel depot containing paclitaxel (PTX) nanocrystals (PNC). PNC suppressed SKOV3 cell proliferation more efficiently than microparticulate PTX precipitates (PPT), and the gel containing PNC (PNC-gel) showed a lower maximum tolerated dose than PPT-containing gel (PPT-gel) in mice, indicati… Show more
“…Therefore, these findings do not support the expected synergy between the residence time of the drug and its therapeutic effect. The same research group evaluated the efficacy of PTX nanocrystals and microparticulate PTX precipitates loaded on a similar crosslinkable HA hydrogel for the treatment of mice bearing SKOV-3 ovarian cancer tumors [87]. Contrary to outcomes obtained with the PtNP/gel, the PTX nanocrystals exhibited significant tumor suppression upon single IP administration compared with the commercially available Taxol®.…”
Section: Strategies For Ip Delivery and Sustained Release Of Nanomedimentioning
Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal carcinomatosis (PC). Over the past decade, a lot of effort has been put both in the academia and clinic in developing IP therapeutic approaches that maximize local efficacy while limiting systemic side effects. Also nanomedicines are under investigation for the treatment of tumors confined to the peritoneal cavity, due to their potential to increase the peritoneal retention and to target drugs to the tumor sites as compared to free drugs. Despite the progress reported by multiple clinical studies, there are no FDA approved drugs or formulations for specific use in the IP cavity yet. This review discusses the current clinical management of PC, as well as recent advances in nanomedicines-based IP delivery.We address important challenges to be overcome towards designing optimal nanocarriers for IP therapy in vivo.
“…Therefore, these findings do not support the expected synergy between the residence time of the drug and its therapeutic effect. The same research group evaluated the efficacy of PTX nanocrystals and microparticulate PTX precipitates loaded on a similar crosslinkable HA hydrogel for the treatment of mice bearing SKOV-3 ovarian cancer tumors [87]. Contrary to outcomes obtained with the PtNP/gel, the PTX nanocrystals exhibited significant tumor suppression upon single IP administration compared with the commercially available Taxol®.…”
Section: Strategies For Ip Delivery and Sustained Release Of Nanomedimentioning
Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal carcinomatosis (PC). Over the past decade, a lot of effort has been put both in the academia and clinic in developing IP therapeutic approaches that maximize local efficacy while limiting systemic side effects. Also nanomedicines are under investigation for the treatment of tumors confined to the peritoneal cavity, due to their potential to increase the peritoneal retention and to target drugs to the tumor sites as compared to free drugs. Despite the progress reported by multiple clinical studies, there are no FDA approved drugs or formulations for specific use in the IP cavity yet. This review discusses the current clinical management of PC, as well as recent advances in nanomedicines-based IP delivery.We address important challenges to be overcome towards designing optimal nanocarriers for IP therapy in vivo.
“…Intraperitoneal (i.p) chemotherapy in other words the infusion of chemotherapeutic agents directly into the peritoneum is a promising option for ovarian cancer therapy due to spread of the disease to the peritoneal cavity [7,30,31]. Although there are some common drawbacks about i.p administration such as complications related to i.p infusion, including abdominal pain, intolerance to a high level of drug, and discomfort related to the catheter implantation, i.p chemotherapy can be beneficial to maintain an effective local drug concentration for a prolonged period and maximize the locoregional effects on residual tumors [30].…”
Section: Intraperitoneal Chemotherapymentioning
confidence: 99%
“…Although there are some common drawbacks about i.p administration such as complications related to i.p infusion, including abdominal pain, intolerance to a high level of drug, and discomfort related to the catheter implantation, i.p chemotherapy can be beneficial to maintain an effective local drug concentration for a prolonged period and maximize the locoregional effects on residual tumors [30]. Another problem about i.p chemotherapy is rapid clearance of small molecule drugs from peritoneal cavity and necessity of frequent dosing [30]. In order to increase the residence time of the chemotherapeutics in the peritoneal cavity controlled release drug carriers, such as microparticles, hydrogels and bioadhesive nanoparticels [31].…”
Section: Intraperitoneal Chemotherapymentioning
confidence: 99%
“…PNC were more cytotoxic than microparticulate PTX in SKOV3 cell culture due to cellular PTX retention. After single dose intraperitoneal administration in vivo studies demonstrated that PNC-gel was more toxic than microparticulate PTX gel and extended survival of tumor-bearing mice because of greater antitumor effect than microparticulate PTX gel and free drug [30] (Table 1).…”
“…We have reported that mesoporous silica nanoparticles (MSNs) were able to predominately accumulate in tumors following intraperitoneal (IP) administration in a metastatic ovarian cancer mouse model, likely due to the specific interaction between MSNs and the tumor surface . IP‐injected MSNs are largely retained in the peritoneal cavity with a high probability of interacting with tumor tissues, while intravenously (IV) injected NPs are mostly deposited in the liver and spleen . Taking advantage of this finding, we designed a core/shell structure of MSNs with contrast agents both in the core and in the shell to maximize the contrast ability, and also to retain the silica surface properties for interacting with tumors.…”
Nonspecific high‐energy radiation for treatment of metastatic ovarian cancer is limited by damage to healthy organs, which can be mitigated by the use of radiosensitizers and image‐guided radiotherapy. Gold (Au) and tantalum oxide (TaOx) nanoparticles (NPs), by virtue of their high atomic numbers, find utility in the design of bimetallic NP systems capable of high‐contrast computed tomography (CT) imaging as well as a potential radiosensitizing effect. These two radio‐dense metals are integrated into dendritic mesoporous silica NPs (dMSNs) with radial porous channels for high surface‐area loading of therapeutic agents. This approach results in stable, monodispersed dMSNs with a uniform distribution of Au on the surface and TaOx in the core that exhibits CT attenuation up to seven times greater than iodine or monometallic dMSNs without either TaOx or Au. Tumor targeting is assessed in a metastatic ovarian cancer mouse model. Ex vivo micro‐CT imaging of collected tumors shows that these NPs not only accumulate at tumor sites but also penetrate inside tumor tissues. This study demonstrates that after intraperitoneal administration, rationally designed bimetallic NPs can simultaneously serve as targeted contrast agents for imaging tumors and to enhance radiation therapy in metastatic ovarian cancer.
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