Organ distribution of cisplatin after intraperitoneal administration of cisplatin-loaded microspheres

Tamura, Takashi; Imai, Jun; Matsumoto, Akira; Tanimoto, Masahiko; Suzuki, Akira; Horikiri, Yuji; Suzuki, Takehiko; Yoshino, Hideaki; Ike, Osamu

doi:10.1016/s0939-6411(02)00037-1

Cited by 28 publications

(22 citation statements)

References 15 publications

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“…Gelatin nanoparticles (NPs) (600 nm) [16] or polymeric NPs (265 nm) [22] were also considered for IP drug delivery, although their abilities to control drug release and persist in the peritoneal cavity were quite limited [16, 22]. In this regard, larger particles (4–6 μm [16, 23] or 47 μm [24]) were found to be superior to NPs in their retention in the peritoneal cavity and maintenance of drug level [16]. Similarly, 1 μm liposomes were better retained in the peritoneal cavity than 100 nm liposomes [25].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors

Bajaj

Kim

Mohammed

et al. 2012

Journal of Controlled Release

126

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Intraperitoneal (IP) chemotherapy is an effective way of treating local and regional malignancies confined in the peritoneal cavity such as ovarian cancer. However, a persistent major challenge in IP chemotherapy is the need to provide effective drug concentrations in the peritoneal cavity for an extended period of time. We hypothesized that hyaluronic acid (HA)-based in-situ crosslinkable hydrogel would serve as a carrier of paclitaxel (PTX) particles to improve their IP retention and therapeutic effects. In-vitro gel degradation and release kinetics studies demonstrated that HA gels could entrap microparticulate PTX (>100 μm) and release the drug over 10 days, gradually degraded by hyaluronidase, but had limited effect on retention of Taxol, a 14-nm micelle form of PTX. When administered IP to tumor-bearing nude mice, PTX was best retained in the peritoneal cavity as PTX-gel (microparticulate PTX entrapped in the HA gel), whereas Taxol-gel and other Taxol-based formulations left negligible amount of PTX in the cavity after 14 days. Despite the increase in IP retention of PTX, PTX-gel did not further decrease the tumor burdens than Taxol-based formulations, presumably due to the limited dissolution of PTX. This result indicates that spatial availability of a drug does not necessarily translate to the enhanced anti-tumor effect unless it is accompanied by the temporal availability.

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Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors

Bajaj

Kim

Mohammed

et al. 2012

Journal of Controlled Release

126

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“…Partly due to this reason, recent studies comparing drug concentrations in the peritoneal cavity, plasma, and major organs after IP administration of different particle formulations concluded that microparticles, whose sizes range from 4 to 6 µm (32,33) to 47 µm (39), were an optimal formulation for IP administration. Microparticles were cleared from the peritoneal cavity relatively slowly and had a better ability to retain the drug (32,33).…”

Section: Drug Delivery Systems For Ip Therapymentioning

confidence: 99%

Drug Delivery Systems for Intraperitoneal Therapy

Bajaj

Yeo

2010

Pharm Res

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Disorders associated with the peritoneal cavity include peritoneal adhesions and intraperitoneal (IP) malignancies. To prevent peritoneal adhesions, physical barrier devices are used to prevent organs from contacting other structures in the abdomen and forming adhesions, or pharmacological agents that interfere with adhesion formation are administered intraperitoneally. IP malignancies are other disorders confined to the peritoneal cavity, which are treated by combination of surgical removal and chemotherapy of the residual tumor. IP drug delivery helps in the regional therapy of these disorders by providing relatively high concentration and longer half-life of a drug in the peritoneal cavity. Various studies suggest that IP delivery of anti-neoplastic agents is a promising approach for malignancies in the peritoneal cavity compared to the systemic administration. However, IP drug delivery faces several challenges, such as premature clearance of a small molecular weight drug from the peritoneal cavity, lack of target specificity, and poor drug penetration into the target tissues. Previous studies have proposed the use of micro/nanoparticles and/or hydrogel-based systems for prolonging the drug residence time in the peritoneal cavity. This commentary discusses the currently used IP drug delivery systems either clinically or experimentally and the remaining challenges in IP drug delivery for future development.

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“…The first-line treatment of ovarian cancer involves use of platinum based chemotherapeutic agents, such as cisplatin along with other anti-cancer drugs such as paclitaxel [4][5][6]. Cisplatin is widely used for the treatment of peritoneal carcinomatosis by Intraperitoneal (IP) administration [7,8]. Although clinical studies have demonstrated the superior efficacy of IP chemotherapy of cisplatin compared to Intravenous (IV) chemotherapy, IP cisplatin chemotherapy suffers from major drawbacks, such as poor penetration of cisplatin into peritoneal tumors and dose-limiting systemic toxicity due to infiltration of cisplatin into systemic circulation through peritoneum.…”

Section: Methodsmentioning

confidence: 99%

In vivo Efficacy of PAMAM-Dendrimer-Cisplatin Complexes in SKOV-3 Xenografted Balb/C Nude Mice

Yellepeddi¹,

Vangara²

2013

J Biotechnol Biomaterial

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Loco-regional delivery of cisplatin by Intraperitoneal (IP) administration in ovarian cancer is highly advantageous, since it exposes high concentrations of cisplatin to tumors in the peritoneal cavity. PAMAM-dendrimer-cisplatin complexes are expected to enhance the penetration of tumors in the peritoneal cavity, and aid in enhancing antitumor efficacy of cisplatin. In the present study, PAMAM G 4 NH 2 and Biotin PAMAM G 4 NH 2 dendrimer cisplatin complexes were administered intraperitoneally to SKOV xenografted athymic nude mice at a dose of 4 mg/kg. The increase in lifespan of tumor bearing mice and biodistribution of cisplatin in various organs was evaluated after IP administration of cisplatin and dendrimer-cisplatin complexes. The lifespan of mice increased by 41.93% and 25.8%, after treatment with PAMAM G 4 NH 2 and Biotin PAMAM G 4 NH 2 dendrimer cisplatin complexes, respectively. A 3-fold increase in the levels of platinum in plasma was observed, after administration of both PAMAM G 4 NH 2 and Biotin PAMAM G 4 NH 2 dendrimer cisplatin complexes. Biodistribution studies have shown higher accumulation of platinum in liver, spleen and kidneys with PAMAM G 4 NH 2 dendrimer-cisplatin complexes. The increased plasma concentration and enhanced tissue accumulation after IP administration of dendrimer-cisplatin complexes offer advantage of administering low dose of cisplatin, which would reduce the dose-dependent toxic effects of cisplatin.

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Organ distribution of cisplatin after intraperitoneal administration of cisplatin-loaded microspheres

Cited by 28 publications

References 15 publications

Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors

Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors

Drug Delivery Systems for Intraperitoneal Therapy

In vivo Efficacy of PAMAM-Dendrimer-Cisplatin Complexes in SKOV-3 Xenografted Balb/C Nude Mice

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