In Vitro Evaluation of the Safety and Antineoplastic Effects in Gastrointestinal Tumors of Nanostructured Lipid Carriers Loaded with Berberine.

in Pharmaceutics by Denitsa Stefanova, Yordan Yordanov, Radostina Bogdanova, Christina Voycheva, Borislav Tzankov, Teodora Popova, Magdalena Kondeva-Burdina, Virginia Tzankova, Natalia Toncheva-Moncheva, Diana Tzankova, Marta Slavkova

TLDR

  • The study develops a nanosized drug delivery system for berberine, a benzylisoquinoline alkaloid with anticancer properties, to improve its aqueous solubility and application.

Abstract

: Natural substances have been a widely studied source of both pharmaceutical excipients and drugs. Berberine (BRB) is a benzylisoquinoline alkaloid isolated from different plant sources. It possesses various pharmacological properties including antibacterial, antitumor, antidiabetic, neuroprotective, hepatoprotective, anti-inflammatory, antioxidant, etc. However, the limited aqueous solubility hinders its application. Nanosized drug delivery systems are an innovative approach for addressing various challenges regarding drug delivery via different routes of administration. Their utilization could improve the solubility of active constituents.: A melt-emulsification and ultrasonication technique was applied for the preparation of nanostructured lipid carriers (NLCs). They were thoroughly physicochemically characterized by the means of Dynamic Light Scattering, TEM, FTIR, DSC, TGA, and In Vitro release. The In Vitro efficacy and safety were evaluated on cholangiocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, lymphoma, fibroblast, and cardioblast cells, as well as rat liver microsomes by means of cytotoxicity assays and the comet assay.: The obtained nanoparticles had a spherical shape and size around 158.2 ± 1.8 nm with negative zeta potential. They revealed successful drug loading and improved dissolution of berberine in physiological conditions. The In Vitro safety studies showed that loading BRB in NLCs resulted in improved or retained cytotoxicity to tumor cell lines and reduced cytotoxicity to normal cell lines and liver microsomes. The NLC itself increased microsomal malondialdehyde (MDA) and comet formation.: A successful preparation of NLCs with berberine is presented. The nanocarriers show favorable physicochemical and biopharmaceutical properties. The cellular experiments show that the NLC loading of berberine could improve its anticancer efficacy and safety. These findings highlight the potential applicability of berberine in gastrointestinal neoplasms and build the foundation for future practical translation.

Overview

  • The study aims to develop a nanosized drug delivery system for berberine, a benzylisoquinoline alkaloid with pharmacological properties, to enhance its aqueous solubility and application.
  • The researchers prepared nanostructured lipid carriers (NLCs) using a melt-emulsification and ultrasonication technique and characterized them physicochemically.
  • The primary objective of the study is to evaluate the in vitro efficacy and safety of berberine-loaded NLCs in various types of cancer cells and normal cells, as well as rat liver microsomes.

Comparative Analysis & Findings

  • The obtained nanoparticles had a spherical shape and size around 158.2 ± 1.8 nm with negative zeta potential, indicating successful drug loading and improved dissolution of berberine.
  • The NLC-loaded berberine showed improved or retained cytotoxicity to tumor cell lines and reduced cytotoxicity to normal cell lines and liver microsomes in in vitro studies.
  • The NLC itself increased microsomal malondialdehyde (MDA) and comet formation, indicating potential biocompatibility and toxicity concerns.

Implications and Future Directions

  • The findings highlight the potential applicability of berberine in gastrointestinal neoplasms and demonstrate the feasibility of developing NLCs as a delivery system for improving its anticancer efficacy and safety.
  • Future studies should investigate the in vivo efficacy and toxicity of berberine-loaded NLCs in preclinical models and explore various formulations and routes of administration to optimize their application.
  • The study's results establish a foundation for practical translation and suggest that berberine-loaded NLCs could be a valuable therapeutic approach for treating gastrointestinal neoplasms.
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