Fucoidan/hyaluronic acid cross-linked zein nanoparticles loaded with fisetin as a novel targeted nanotherapy for oral cancer.

Fisetin (FS) is an anticancer drug having potential role in oral tumors management. However, its clinical application is limited due to its hydrophobicity and instability. Bioactive polymers-based nanosystems have a great potential in cancer therapy. Herein, different biopolymers were selected for their anticancer activity and targeting ability for nanoparticles preparation namely; fucoidan (FU), zein (Zn) and hyaluronic acid (HA). The selected FS-loaded cross-linked Zn nanoparticles (ZFH) which contains HA& FU for Zn nanoparticles stabilization showed the most suitable particle size (196 ± 6.53 nm), mean surface net charge (-38.8 ± 1.47 mV) and entrapment efficiency (98 ± 1.2 %). This is the first study to utilize both HA &FU not only for stabilization but also for dual targeting effect due to their targeting ability to multiple tumor targets. In-vitro anticancer activity of ZHF revealed remarkable uptake by SCC-4 cells with significant cytotoxic action. Further, ZHF was appraised using 4-nitroquinoline 1-oxide (4-NQO)-induced oral cancer in-vivo; ZHF significantly reduced OSCC-specific serum biomarkers levels, histologic tumor grade and increased caspase-3 level. Moreover, potential of destroying two key tumor regulatory cells; TECs and CSCs, was evaluated using their specific markers. The elaborated ZFH nanoparticles could be considered as promising targeted nanotherapy for oral cancer treatment with enhanced efficacy and survival rate.

Gel in core carbosomes as novel ophthalmic vehicles with enhanced corneal permeation and residence.

Carbopol is a good bio-adhesive polymer that increases the residence time in the eye. However, the effect of blinking and lacrimation still reduce the amount of polymer and the incorporated drug available for bioadhesion. Gel-core liposomes are advanced systems offering benefits making it a good tool for improved ocular drug delivery and residence time. Incorporation of carbopol in gel-core liposomes and their potential in ocular delivery have not so far been investigated. Fluconazole (FLZ) was selected as a challenging important ocular antifungal suffering from poor corneal permeation and short residence time. In this study, gel-core carbosomes have been elaborated as novel carbopol-based ophthalmic vehicles to solve ocular delivery obstacles of FLZ and to sustain its effect. Full in vitro appraisal was performed considering gel-core structure, entrapment efficiency, particle size and stability of the vesicles as quality attributes. Structure elucidation of the nanocarrier was performed using optical, polarizing and transmission electron microscopy before and after Triton-X100 addition. Ex-vivo ocular permeation and in vivo performance were investigated on male albino rabbits. Optimized formulation (CBS5) showed gel-core structure, nanosize (339.00 ±â€¯5.50 nm) and not defined before (62.00% ±â€¯1.73) entrapment efficiency. Cumulative amount of CBS5 permeated ex-vivo after 6 h, was 2.43 and 3.43 folds higher than that of conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of CBS5 showed significantly higher AUC0-24 h (487.12 ±â€¯74.80) compared to that of FLZ suspension (204.34 ±â€¯7.46) with longer residence time in the eye lasts for more than 18 h. In conclusion, novel gel-core carbosomes could successfully be used as a promising delivery system for chronic ocular diseases.

Hyalugel-integrated liposomes as a novel ocular nanosized delivery system of fluconazole with promising prolonged effect.

Fungal infections need long-term therapy with the proper antifungal agent. Despite effectiveness, Fluconazole (FLZ) ocular delivery is constrained by limited penetration, short residence time, in addition to the common barriers of the eye. Hyalugel-integrated liposomes were designed as novel ocular delivery systems integrating hyaluronic acid (HA) inside and surrounding vesicles by a simple preparation technique. The impact of combining HA hydrogel and liposomes was investigated in a series of different formulations. Full in-vitro optimization was performed regarding; HA and FLZ concentration, entrapment efficiency, particle size and stability to select the formula with the best characteristics. Structure elucidation of gel integration was done using polarizing and transmission electron microscopes before and after Triton-X100 addition. Corneal deposition and permeation were examined ex-vivo and in-vivo on male albino rabbits. Selected formulation (HYS7) showed gel-integrated structure, nanosize (218.50±4.50nm) and % EE 42.81%±1.66. Ex-vivo cumulative corneal permeation of FLZ after 6h from HYS7, was 2.99 and 4.18 folds higher than conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of HYS7 showed unprecedented sustained effect of FLZ reaching 24h. In conclusion, novel hyalugel-integrated liposomes significantly enhanced corneal permeability compared to conventional liposomes and FLZ suspension. They would be promising alternates for eye drops; decreasing frequency of administration and increasing patients' compliance.