Surface-coated PLA nanoparticles loaded with temozolomide for improved brain deposition and potential treatment of gliomas: development, characterization and in vivo studies

Abstract

Hydrophobicity of PLA nanoparticles makes them a good substrate for macrophageal and reticulo-endothelial system uptake. Long-circulating properties can be imparted to these particles by coating them with hydrophilic stabilizers. Surface-modified PLA nanoparticles loaded with anti-cancer agent temozolomide were fabricated by solvent evaporation method and coated with surface modifiers. Selection of the surface modifier was based upon uptake of nanoparticles by K9 cells (liver cells). The particles were prepared and characterized for various physicochemical properties using transmission electron microscopy, differential scanning calorimetry, powder X-ray diffraction and in vitro dissolution studies. In vitro BBB permeation studies were performed using the co-culture model developed by using Madin-Darby canine kidney and C6 glioma cells as endothelial and glial cells, respectively. In vitro C6 glioma cell cytotoxicity, cellular proliferation, cellular migration and cellular uptake studies due to developed nanoparticles was assessed. In vivo studies such as pharmacokinetics, qualitative and quantitative biodistribution studies were performed for the developed nanoparticles. Drug-loaded nanoparticles with entrapment efficiency of 50% were developed. PEG-1000 and polysorbate-80 coated nanoparticles were least taken up by the liver cells. Characterization of the nanoparticles revealed formation of spherical shape nanoparticles, with no drug and excipient interaction. In vivo pharmacokinetics of developed nanoparticles depicted enhancement of half-life, area under the curve and mean residence time of the drug. Qualitative and quantitative biodistribution studies confirmed enhanced permeation of the drug into the brain upon loading into nanoparticles with less deposition in the highly perfused organs like lung, liver, spleen, heart and kidney.

Polymeric lipid vesicles with pH-responsive turning on–off membrane for programed delivery of insulin in GI tract

“…It was also found that as the tocopheryl grafting ratio increases, the permeability of FITC-Ins across cellular monolayer enhanced significantly (p50.05). This result is in agreement with the previous reports that surface hydrophobicity plays a significant role in the GI bioavailability of nanoparticles (Sakuma et al, 2001;Jain et al, 2016). The improved surface hydrophobicity facilitates partition of nanoparticles into lipidrich cell membrane due to the mucosa hydrophobic interaction.…”

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering

“…In a recent study, Jain et al, showed that PLA nanoparticles coated with PEG and polysorbate were the least to be taken up by liver and kidney cells in an in-vitro model. This study further demonstrated that by modulating the surface properties, PLA based NPs have the potential for targeted drug delivery [115]. Several methods such as emulsion, nanoprecipitation, salting out, and spray-drying have been reported to encapsulate drugs in in PLA-NPs [116–118].…”

Dendrimer size effects on the selective brain tumor targeting in orthotopic tumor models upon systemic administration

“…For all other organs, both dendrimers do not exhibit accumulation and by 48 hr show less than 0.5 %ID/g, indicating limited systemic exposure to the therapeutic payload. This is in contrast to free drug administration of chemotherapies, which quickly clear from tumor tissue while accumulating in the liver at much greater concentrations 60,76 . These PAMAM dendrimers also compare favorably to gold nanoparticles, PEGylated iron oxide nanoparticles, and other classes of dendrimers, which exhibit slightly higher kidney levels but a significantly greater liver accumulation of 2–70% of the initial dose retained 49,50,54,55,77 .…”