https://orcid.org/0000-0002-3135-8772
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ABSTRACT
Introduction: In selected patients with limited peritoneal metastasis (PM), favorable tumor biology, and a good clinical condition, there is an indication for combination of cytoreductive surgery (CRS) and subsequent intravenous (IV) or intraperitoneal (IP) chemotherapy. Compared with IV injection, IP therapy can achieve a high drug concentration within the peritoneal cavity with low systemic toxicity, however, the clinical application of IP chemotherapy is limited by the related abdominal pain, infection, and intolerance.
Areas covered:To improve the anti-tumor efficacy and safety of IP therapy, various pharmaceutical strategies have been developed and show promising potential. This review discusses the specialized modification of traditional drug delivery systems and demonstrates the preparation of customized drug carriers for IP therapy, including chemotherapy and gene therapy. IP therapy has important clinical significance in the treatment of PM using novel anti-tumor agents as well as conventional drugs in new applications.
Expert opinion: Although IP therapy exhibits good performance both in mouse models and in patients with PM in clinical trials, its clinical application remains limited due to the serious side effects and low acceptability. Further investigations, including pharmaceutical strategies, are needed to develop potential IP therapy, focusing on the efficacy and safety thereof.
Article highlights
Following IP chemotherapy, a high drug concentration can be achieved within the peritoneal cavity, with low systemic toxicity and enhanced therapeutic effect.
In order to improve the antitumor activity and safety of commonly used drugs in IP therapy, many pharmaceutical strategies have been developed, including synthesising drug complexes, preparing novel nano/microscale drug delivery systems, and modifying and repurposing traditional drug carriers with new functions. In this review, pharmaceutical strategies were classified by their functions in IP chemotherapy.
For PM, therapeutic genes can be delivered directly to tumours by IP injection, with high therapeutic efficiency and tumour specificity, but without inducing toxic side effects to healthy organs or cells.
Some novel antitumor agents and conventional drugs in new application provide good performance in preclinical studies, but do not produce positive results in clinical trials owing to an ineffective concentration or serious systemic toxicity. For these drugs, the IP route may be a potential approach to prove their antitumor activity.
Although IP therapy has exhibited good performance both in mouse models and in patients with PM in clinical trials, clinical application remains limited due to the serious side effects and its low acceptability. Further investigations are needed to develop potential IP therapy, focusing on the efficacy and safety.
This box summarizes key points contained in the article.
Abbreviations
| PC | = | Peritoneal carcinomatosis |
| IP | = | Intraperitoneal |
| CRS | = | Cytoreductive surgery |
| NCI | = | National Cancer Institute |
| MDR | = | Multidrug resistance |
| HIPEC | = | Hyperthermic intraperitoneal chemotherapy |
| PIPAC | = | Pressurized intraperitoneal aerosol chemotherapy |
| PL A | = | Poly(dl-lactic acid) |
| PLG | = | Poly(lactide-co-glycolide) |
| PCL-PEG-PCL | = | Poly (e-caprolactone) poly (ethyleneglycol) poly (e-caprolactone) |
| BMEDA | = | N,N-bis(2-mercaptoethyl)-N9,N9-diethyle thylenediamine |
| HA | = | Hyaluronic acid |
| ED-catalase | = | Ethylenediamine-conjugated catalase |
| PECE | = | Poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) |
| PECT | = | Poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly (ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone) |
| Plu-CLA | = | Poly(organophosphazenes) and conjugated linoleic acid-incorporated Pluronic F-127 |
| RES | = | Reticuloendothelial system |
| MSNs | = | Mesoporous silica nanoparticles |
| P-PEG-UCNPs | = | PEG-coated lanthanide-loaded upconversion nanoparticles |
| MSNs | = | Mesoporous silica nanoparticles |
| POEGMA | = | Poly(oligoethylene glycol methacrylate) |
| PDPA | = | Poly(2-(diisopropylamino)ethyl methacrylate) |
| ASCs | = | Adipose-derived stem cells |
| NSCs | = | Neural stem cells |
| CHEMS | = | Cholesteryl hemisuccinate |
| PLL | = | Poly-L-lysine |
| US | = | Ultrasound |
| UTMD | = | Utrasound-mediated microbubble destruction |
| LHRH | = | Luteinizing hormone-releasing hormone |
| TAMs | = | Tumor-associated macrophages |
| PDT | = | Photodynamic therapy |
| WSDP | = | Water-soluble derivative of propolis |
| TPM | = | Tumor penetrating microparticles |
| ABC | = | ATP-binding cassette |
| CEP | = | Cepharanthine |
| HSV-TK | = | Herpes simplex virus thymidine kinase suicide gene |
| Man-Ad5 | = | Mannan-conjugated adenovirus |
| PEI | = | Polyethyleneimine |
| PEG-PEI | = | PEGylated PEI |
| PQDEA | = | Poly (N-[2-(acryloyloxy)ethyl] -N-[p-acetyloxyphenyl]- N,N-diethylammoniumchloride) |
| ROS | = | Reactive oxygen species |
| B-PDEAEA | = | Poly[(2-acryloyl)ethyl(p-boronic acid benzyl) diethylammonium bromide] |
| DOTAP | = | 1,2-Dioleoyl-3-trimethylammonium-propane |
| DOPE | = | Dioleyl phosphatidyl ethanolamine |
| AuNPs | = | Gold nanoparticles |
| 5-FU | = | 5-Fluorouracil |
| P-DPP | = | Low-dosage paclitaxel encapsulated nanoparticles |
| PCat | = | PEGylated cationic liposome |
| PPI | = | Poly (Propyleneimine) |
| LHRH | = | Hormone-Releasing Hormone |
| PCX | = | Cholesterol-modified polymeric nanoparticles |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.