Development of a nanocapsule-loaded hydrogel for drug delivery for intraperitoneal administration
Intraperitoneal (IP) drug delivery of chemotherapeutic agents, administered through hyperthermal intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosolized chemotherapy (PIPAC), is effective for the treatment of peritoneal malignancies. However, these therapeutic interventions are cumbersome in terms of surgical practice and are often associated with the formation of peritoneal adhesions, due to the catheters inserted into the peritoneal cavity during these procedures. Hence, there is a need for the development of drug delivery systems that can be administered into the peritoneal cavity. In this study, we have developed a nanocapsule (NCs)-loaded hydrogel for drug delivery in the peritoneal cavity. The hydrogel has been developed using poly(ethylene glycol) (PEG) and thiol-maleimide chemistry. NCs-loaded hydrogels were characterized by rheology and their resistance to dilution and drug release were determined in vitro. Using IVIS® to measure individual organ and recovered gel fluorescence intensity, an in vivo imaging study was performed and demonstrated that NCs incorporated in the PEG gel were retained in the IP cavity for 24 h after IP administration. NCs-loaded PEG gels could find potential applications as biodegradable, drug delivery systems that could be implanted in the IP cavity, for example at a the tumour resection site to prevent recurrence of microscopic tumours.
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About this article: Bhanu Teja Surikutchi, Rebeca Obenza-Otero, Emanuele Russo, Mischa Zelzer, Irene Golán Cancela, José A. Costoya, José Crecente Campo, Maria José Alonso, Maria Marlow, Development of a nanocapsule-loaded hydrogel for drug delivery for intraperitoneal administration, International Journal of Pharmaceutics, Volume 622, 2022, 121828, ISSN 0378 5173, https://doi.org/10.1016/j.ijpharm.2022.121828. (https://www.sciencedirect.com/science/article/pii/S0378517322003830)
Materials
Fibrinogen and thrombin, both from human blood plasma were purchased from Sigma-Aldrich, Spain. Different molecular weights (Mn) of HA (research grade), 41–65 kDa, 500–749 kDa and 1.01–1.8 MDa, were purchased from Lifecore, USA. Tween® 80, good manufacturing practice (GMP) grade, was purchased from Acofarma, Spain. Lipocol® HCO-40 was obtained from Lipo Chemicals, USA. Labrasol and Labrafac™ Lipophile WL1349 (EP and USP compliant grades) were procured from Gattefossé, France. Benzethonium chloride (BZT) was purchased from Spectrum, USA. DXM (99.7% purity) was purchased from Acofarma, Spain. DCX (98% purity) was purchased from Acros Organics, Thermo Fisher Scientific, UK. PEG (Mn 3350) and fluorescent label, 1,1″-dioctadecyl-3,3,3″,3″-tetramethylindotricarbocyanine iodide (DiR) was purchased from Thermo Fisher Scientific, UK. 4-arm PEG maleimide (PEG-MAL, Mn 10 kDa) was purchased from Advanced BioChemicals, LLC, USA, while p-toluenesulfonic acid, dithiothreitol (DTT), 3-mercaptopropionic acid, HEPES, Bovine serum albumin (BSA) (≥98%), sodium chloride (NaCl), sodium azide (NaN3), calcium chloride dihydrate (CaCl2·2H2O), potassium chloride (KCl), magnesium chloride (MgCl2), sodium phosphate dibasic (Na2HPO4), potassium phosphate monobasic (KH2PO4) was purchased from Sigma-Aldrich®, UK. Phosphate buffer saline (PBS, 0.01 M) tablets were also procured from Sigma-Aldrich®, UK. 1 M Tris buffer (pH 8.0) was purchased from Thermo Fisher Scientific, UK. All organic solvents used were HPLC grade. In-house ultrapure (Milli-Q) or endotoxin-free water was used throughout the experiments. Laboratory glassware was previously sterilized in an autoclave (Systec, Germany) prior to in vivo experiments and preparation carried out in a laminar flow unit.