Preparation and characterization of dextran-zein-curcumin nanoconjugate for enhancement of curcumin bioactivity.

Curcumin is one of the most important polyphenolic nutrients in pharmaceutical industries. Unfortunately, its poor solubility and bioavailability have hampered its clinical application. To improve curcumin solubility and bioavailability, a natural nanocarrier made from protein-polysaccharide conjugate has been developed. Following antisolvent precipitation method, zein (Z) nanoparticles coated with dextran sulphate (DS) have been fabricated as curcumin (C) nanocarrier (DSZCNPs). The physicochemical properties of the nanoconjugate were measured using different techniques. Morphologically, DSZCNPs appeared spherical and monodispersed in scanning electron microscope (SEM) and transmission electron microscope (TEM) images. Curcumin encapsulation efficiency was ≈ 96%. DSZCNPs size was 180 nm and the polydispersity index value (PDI) 0.28. Zeta potential for DSZCNPs was -28.5 mV. DSZCNPs showed stability either for shelf storage (100 days) or at different pHs. Furthermore, DSZCNPs protected zein nanoparticles degradation in gastric environment and achieved controlled curcumin release in intestinal environment. DSZCNPs greatly enhanced the antioxidant activity of curcumin as demonstrated by DPPH assay. DSZCNPs had significant results in the reduction of colony forming unit (CFU%) against the tested microbes when compared with free curcumin. Also, the anticancer activity of DSZCNPs and free curcumin against hepatocellular carcinoma cells (HepG2) were assessed by MTT assay. IC50 for DSZCNPs was 13 µg/ml compared to 50 µg/ml for free curcumin indicating the therapeutic impact of DSZCNPs over free curcumin.Based on the above results, the developed zein-dextran nanocomplex exhibited high stability and improved the efficacy and bioactivity of curcumin suggesting its potential utility as nanovehicle for the hydrophobic drug curcumin.

Bioinspired synthesis of protein/polysaccharide-decorated folate as a nanocarrier of curcumin to potentiate cancer therapy.

Curcumin is a promising anticancer agent, but its clinical utilization has been hindered by its low solubility and bioaccessibility. To overcome these obstacles, we developed a natural protein-polysaccharide nanocomplex made from casein nanoparticles coated with a double layer of alginate and chitosan and decorated with folic acid (fCs-Alg@CCasNPs) for use as a nanocarrier for curcumin. The developed nanoformulation showed a drug encapsulation efficiency = 75%. The measured size distribution of fCs-Alg@CCasNPs was 333.8 ± 62.35 nm with a polydispersity index (PDI) value of 0.179. The recorded zeta potential value of fCs-Alg@CCasNPs was 28.5 mV. Morphologically, fCs-Alg@CCasNPs appeared spherical, as shown by transmission electron microscopy (TEM). The successful preparation of fCs-Alg@CCasNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy of all the constituents forming the nanoformulation. Further in vitro investigations indicated the stability of fCs-Alg@CCasNPs as well as their controlled and sustained release of curcumin in the tumor microenvironment. Compared with free curcumin, fCs-Alg@CCasNPs induced a higher cytotoxic effect against a pancreatic cancer cell line. The in vivo pharmacokinetics of fCs-Alg@CCasNPs showed a significant AUC0-24 = 2307 ng.h/ml compared to 461 ng.h/ml of free curcumin; these results indicated high curcumin bioavailability in plasma. The in vivo results of tumor weight, the amount of DNA damage measured by comet assay and histopathological examination revealed that treating mice with fCs-Alg@CCasNPs (either intratumorally or intraperitonially) prompted higher therapeutic efficacy against Ehrlich carcinoma than treatment with free curcumin. Therefore, the incorporation of curcumin with protein/polysaccharide/folate is an innovative approach that can synergistically enhance curcumin bioavailability and potentiate cancer therapy with considerable biosafety.

Multifunctional magnetic-gold nanoparticles for efficient combined targeted drug delivery and interstitial photothermal therapy.

Abundant efforts have recently been made to design potent theranostic nanoparticles, which combine diagnostic and therapeutic agents, for the effective treatment of cancer. In this study, we developed multifunctional magnetic gold nanoparticles (MGNPs) that are able to (i) selectively deliver the drug to the tumor site in a controlled-release manner, either passively or by using magnetic targeting; (ii) induce photothermal therapy by producing heat by near-infrared (NIR) laser absorption; and (iii) serve as contrast agents for magnetic resonance imaging (MRI) (imaging-guided therapy). The prepared MGNPs were characterized by different physical techniques. They were then coated and conjugated with polyethylene glycol (PEG) and doxorubicin (DOX) to form MGNP-DOX conjugates. The high efficacy of MGNP-DOX for combined chemo-photothermal therapy was observed both in vitro and in vivo. The effectiveness of MGNP-DOX as theranostic nanoparticles was confirmed by histopathological examination and immunohistochemical studies. Moreover, MGNP-DOX showed good potential as MRI contrast agents for guided chemo-photothermal synergistic therapy.

Enhancement of the ocular therapeutic effect of prednisolone acetate by liposomal entrapment.

Eye drops account for 90% of ophthalmic formulations despite of the rapid precorneal drug loss. Our aim is to test the effect of positive charge induction and the subsequent size reduction on the efficiency of liposomes as ocular drug delivery system for the lipophilic drug prednisolone acetate (PSA). Different formulations of PSA-loaded liposomes, positive multilamellar liposomes (pMLV), positive small (nano-sized) unilamellar liposomes (pSUV) and neutral multilamellar liposomes (nMLV), were prepared. These formulations were characterized by measuring surface charge, size distribution, entrapment efficiency, release rate, and ability to deliver PSA across the cornea. In vitro studies showed that positive charge induction reduces the transcorneal flux (about 1.9-fold lower than nMLV), while the subsequent size reduction results in higher flux (about 1.2-fold higher than nMLV). But in vivo results revealed that pSUV produced more concentrations of PSA in aqueous humor than nMLV (P < 0.05) suggesting greater chance for drug penetration, pSUV were more effective than nMLV in this regard (P < 0.05). As revealed by in vivo studies and ophthalmic examinations, positive charge induction and the subsequent size reduction increased the efficiency of liposomes as ocular drug delivery system for PSA.