Gelatin and collagen-mimetic nanoparticles for intraperitoneal cisplatin delivery: From synthesis to in-vivo SPECT imaging of biodistribution.

Peritoneal carcinomatosis is a metastatic condition with poor prognosis, commonly associated with abdominal cancers. Current treatments comprise cytoreductive surgery with systemic chemotherapy or may include more invasive options such as hyperthermic intraperitoneal chemotherapy, and pressurized intraperitoneal aerosol chemotherapy. However, currently, all treatment options are considered palliative as remaining cancer cells cause recurrence. This study explores new intraperitoneal drug delivery systems based on gelatin-poly(glutamic acid) (Gel-PGA-NPs) or collagen-like-peptide-poly(glutamic acid) nanoparticles (CLP-PGA-NPs) loaded with cisplatin for localized treatment of peritoneal carcinomatosis. These NPs, synthesized via in situ polymerization, offer prolonged drug release and continuous biodegradation. The used CLP is produced by a recombinant manufacturing method avoiding any animal-derived material, which has advantages in regard to biocompatibility and reproducibility. Characterization by dynamic light scattering and transmission electron microscopy showed NPs averaging 150 nm in size. Cisplatin loading in CLP-PGA NPs facilitated high drug loading and stability compared to Gel-PGA NPs. SPECT/CT imaging of radiolabeled NPs in healthy mice revealed primary uptake in the spleen and liver, and further accumulation in the pancreas, ovaries and adherence to abdominal tissues highlighting the potential use for treatment of intraperitoneal metastases.