Search Results (5)

Cancer is still one of the major diseases worldwide. The discovery of new drugs and the improvement of existing ones is one of the areas of priority in the fight against cancer. Dioxadet ([5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol) represents one of the promising 1,3,5-triazine derivatives and has cytostatic activity towards ovarian cancer. In this study, we first report the development of dioxadet-bearing nanomedicines based on block-copolymers of poly(ethylene glycol) monomethyl ether (mPEG) and poly(D,L-lactic acid) (PLA)/poly(ε-caprolactone) (PCL) and then conduct an investigation into their characteristics and properties. The preparation of narrow-sized nanoparticles with a hydrodynamic diameter of 100–120 nm was optimized using a nanoprecipitation approach. Thoughtful optimization of the preparation of nanomedicines was carried out through adjustments to the polymer’s molecular weight, the pH of the aqueous medium used for nanoprecipitation, the initial drug amount in respect to the polymer, and polymer concentration in the organic phase. Under optimized conditions, spherical-shaped nanomedicines with a hydrodynamic diameter of up to 230 nm (PDI < 0.2) containing up to 592 ± 22 μg of dioxadet per mg of polymer nanoparticles were prepared. Study of the drug’s release in a model medium revealed the release up to 64% and 46% of the drug after 8 days for mPEG-b-PLA and mPEG-b-PCL, respectively. Deep analysis of the release mechanisms was carried out with the use of a number of mathematical models. The developed nanoparticles were non-toxic towards both normal (CHO-K1) and cancer (A2780 and SK-OV-3) ovarian cells. A cell cycle study revealed lesser toxicity of nanomedicines towards normal cells and increased toxicity towards cancer cells. The IC₅₀ values determined for dioxadet nanoformulations were in the range of 0.47–4.98 μg/mL for cancer cells, which is close to the free drug’s efficacy (2.60–4.14 μg/mL). The highest cytotoxic effect was found for dioxadet loaded to mPEG-b-PCL nanoparticles. Full article

Biodegradable poly(ethylene glycol)-block-poly(-lactic acid) (PEG-b-PLA) nanoparticles (NPs) were prepared by nanoprecipitation with controlled dimension and with different electric charges, as monitored by dynamic light scattering (DLS). Then NPs were loaded within hydrogels (HG) developed for biomedical applications in the central nervous system, with different pore sizes (30 and 90 nm). The characteristics of the resulting composite hydrogel-NPs system were firstly studied in terms of ability to control the release of small steric hindrance drug mimetic. Then, diffusion-controlled release of different charged NPs from different entangled hydrogels was studied in vitro and correlated with NPs electric charges and hydrogel mean mesh size. These studies showed different trends, that depend on NPs superficial charge and HG mesh size. Release experiments and diffusion studies, then rationalized by mathematical modeling, allowed us to build different drug delivery devices that can satisfy different medical needs. Full article

Southern root-knot nematode (Meloidogyne incognita) is a biotrophic parasite, causing enormous loss in global crop production annually. Abamectin (Abm) is a biological and high-efficiency pesticide against Meloidogyne incognita. In this study, a powerful method, flash nanoprecipitation (FNP), was adopted to successfully produce Abm-loaded nanoparticle suspensions with high drug loading capacity (>40%) and encapsulation efficiency (>95%), where amphiphilic block copolymers (BCPs) poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG), poly(d,l-lactide)-b-poly(ethylene glycol) (PLA-b-PEG), or poly(caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) were used as the stabilizer to prevent the nanoparticles from aggregation. The effect of the drug-to-stabilizer feed ratio on the particle stability were investigated. Moreover, the effect of the BCP composition on the morphology of Abm-loaded nanoparticles for controlling Meloidogyne incognita were discussed. Notably, spindle-like nanoparticles were obtained with PCL-b-PEG as the stabilizer and found significantly more efficient (98.4% mortality at 1 ppm particle concentration) than spherical nanoparticles using PLGA-b-PEG or PLA-b-PEG as the stabilizer. This work provides a more rapid and powerful method to prepare stable Abm-loaded nanoparticles with tunable morphologies and improved effectiveness for controlling Meloidogyne incognita. Full article

Persistence of microorganisms in dentinal tubules after root canal chemo-mechanical preparation has been well documented. The complex anatomy of the root canal and dentinal buffering ability make delivery of antimicrobial agents difficult. This work explores the use of a novel trilayered nanoparticle (TNP) drug delivery system that encapsulates chlorhexidine digluconate, which is aimed at improving the disinfection of the root canal system. Chlorhexidine digluconate was encapsulated inside polymeric self-assembled TNPs. These were self-assembled through water-in-oil emulsion from poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), a di-block copolymer, with one hydrophilic segment and another hydrophobic. The resulting TNPs were physicochemically characterized and their antimicrobial effectiveness was evaluated against Enterococcus faecalis using a broth inhibition method. The hydrophilic interior of the TNPs successfully entrapped chlorhexidine digluconate. The resulting TNPs had particle size ranging from 140–295 nm, with adequate encapsulation efficiency, and maintained inhibition of bacteria over 21 days. The delivery of antibacterial irrigants throughout the dentinal matrix by employing the TNP system described in this work may be an effective alternative to improve root canal disinfection. Full article

In this work, biotin surface functionalized hydrophilic non-water-soluble biocompatible poly(lactic acid) (PLA) nanofibers are created for their potential use as biosensors. Varying concentrations of biotin (up to 18 weight total percent (wt %)) were incorporated into PLA fibers together with poly(lactic acid)-block-poly(ethylene glycol) (PLA-b-PEG) block polymers. While biotin provided surface functionalization, PLA-b-PEG provided hydrophilicity to the final fibers. Morphology and surface-available biotin of the final fibers were studied by Field Emission Scanning Electron Microscopy (FESEM) and competitive colorimetric assays. The incorporation of PLA-b-PEG block copolymers not only decreased fiber diameters but also dramatically increased the amount of biotin available at the fiber surface able to bind avidin. Finally, fiber water stability tests revealed that both biotin and PLA-b-PEG, migrated to the aqueous phase after relatively extended periods of water exposure. The functional hydrophilic nanofiber created in this work shows a potential application as a biosensor for point-of-care diagnostics. Full article