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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731964

ABSTRACT

Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa. It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability. This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained. The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD. In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.


Subject(s)
Cannabidiol , Cytokines , Inflammation , Nanoparticles , Cannabidiol/chemistry , Cannabidiol/pharmacology , Nanoparticles/chemistry , Cytokines/metabolism , Inflammation/drug therapy , Humans , Animals , Free Radicals , Mice , Drug Carriers/chemistry , Lipids/chemistry , Cell Line , Reactive Oxygen Species/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Liposomes
2.
J Drug Target ; : 1-19, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38634290

ABSTRACT

Nanoparticle (NP) functionalization with specific ligands enhances targeted cancer therapy and imaging by promoting receptor recognition and improving cellular uptake. This review focuses on recent research exploring the interaction between cancer cell-expressed chemokine receptor 4 (CXCR4) and ligand-conjugated NPs, utilising small molecules, peptides, and antibodies. Active NP targeting has shown improved tumour targeting and reduced toxicity, enabling precision therapy and diagnosis. However, challenges persist in the clinical translation of targeted NPs due to issues with biological response, tumour accumulation, and maintaining NP quality at an industrial scale. Biological and intratumoral barriers further hinder efficient NP accumulation in tumours, hampering translatability. To address these challenges, the academic community is refocusing efforts on understanding NP biological fate and establishing robust preclinical models. Future studies should investigate NP-body interactions, develop computational models, and identify optimal preclinical models. Establishing central NP research databases and fostering collaboration across disciplines is crucial to expediting clinical translation. Overcoming these hurdles will unlock the transformative potential of CXCR4-ligand-NP conjugates in revolutionising cancer treatment.

3.
ACS Appl Bio Mater ; 6(12): 5426-5441, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-37956113

ABSTRACT

In this study, we synthesized hollow porous iron oxide nanoparticles (HPIONPs) with surface modifications using polymers, specifically chitosan (Chi), polyethylene glycol (PEG), and alginate (Alg), to improve colloidal stability and biocompatibility. For colloidal stability, Alg-coated HPIONPs maintained size stability up to 24 h, with only an 18% increase, while Chi, PEG, and uncoated HPIONPs showed larger size increases ranging from 64 to 140%. The biocompatibility of polymer-coated HPIONPs was evaluated by assessing their cell viability, genotoxicity, and hemocompatibility. Across tested concentrations from 6.25 to 100 µg/mL, both uncoated and polymer-coated HPIONPs showed minimal cytotoxicity against three normal cell lines: RAW264.7, 3T3-L1, and MCF10A, with cell viability exceeding 80% at the highest concentration. Notably, polymer-coated HPIONPs exhibited nongenotoxicity based on the micronucleus assay and showed hemocompatibility, with only 2-3% hemolysis in mouse blood, in contrast to uncoated HPIONPs which exhibited 4-5%. Furthermore, we evaluated the cytotoxicity of HPIONPs on MDA-MB-231 breast cancer cells after a 2 h exposure to a stationary magnetic field, and the results showed the highest cell death of 38 and 29% when treated with uncoated and polymer-coated HPIONPs at 100 µg/mL, respectively. This phenomenon is attributed to iron catalyzing the Fenton and Haber-Weiss reactions, leading to reactive oxygen species (ROS)-dependent cell death (r ≥ 0.98). In conclusion, the hydrothermal synthesis and subsequent surface modification of HPIONPs with polymers showed improved colloidal stability, nongenotoxicity, and hemocompatibility compared to uncoated HPIONPs while maintaining closely similar levels of cytotoxicity against both normal and cancer cells. This research has paved the way for further exploration of polymer coatings to enhance the overall performance and safety profile of magnetic nanoparticles in delivering anticancer drugs.


Subject(s)
Antineoplastic Agents , Chitosan , Mice , Animals , Polymers/chemistry , Porosity , Polyethylene Glycols/chemistry , Chitosan/chemistry , Magnetic Iron Oxide Nanoparticles
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