Triamcinolone-loaded self nano-emulsifying drug delivery systems for ocular use: An alternative to invasive ocular surgeries and injections.

Inflammation of the posterior segment of the eye is a severe condition and hard to cure as delivery of drugs to the inflammation site is inefficient. Currently, the primary treatment approach is ocular surgery or invasive ocular injections. Herein, we designed and developed a topically self nano-emulsifying drug delivery system (SNEDDs) to deliver triamcinolone acetonide (TCA) to the posterior segment of the eye. A screening based on TCA solubility was conducted on each excipient followed by preparation of various formulations using different ratios of the selected excipients. Vesicles of optimized SNEDDs had less than 100 nm size and spherical morphology. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay showed self-emulsified vesicles have relatively high safety on retinal pigment epithelium (RPE) cell line. Furthermore, efficient cellular uptake of coumarin 6-loaded SNEDDs in RPE using confocal laser scanning microscopy (CLSM) was confirmed. In addition, an in-vivo study using hematoxylin and eosin (H&E) staining revealed that 14 days of topical treatment of albino rabbit eyes with TCA-loaded SNEDDs was safe and no sign of tissue destruction and inflammation was detected in different parts of the eye sections including cornea, sclera, retina, and optic nerve. Also, the CLSM images from topically treated eyes with coumarin 6 (a hydrophobic, fluorescent drug model) loaded SNEDDs, showed that the optimized SNEDDs could properly penetrate toward the posterior segments of the eye especially the retina, posterior parts of the choroid, and sclera. Considering the outstanding results obtained by ocular tissue penetration and low toxicity, prepared SNEDDs, have the potential to be used as a topical administration for treating posterior segment disorders of the eye through an utterly non-invasive route and TCA-loaded SNEDDs could be an alternative for TCA intravitreal and intra conjunctival injections.

Theranostic silk sericin/SPION nanoparticles for targeted delivery of ROR1 siRNA: Synthesis, characterization, diagnosis and anticancer effect on triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has the worst prognosis among all breast cancer subtypes. The lack of proper treatments prompted scientists to find a practical targeted therapy to treat this type of tumor. Based on previous studies, tyrosine kinase-like orphan receptor (ROR1) is overexpressed in TNBC cells. Here, we designed a system consisting of superparamagnetic iron oxide nanoparticles (SPIONs) decorated with silk sericin (SS NPs) for the targeted delivery of ROR1 siRNA, a gene silencer to knockdown the expression of human ROR1 gene. NPs exhibited spherical shape of about 193 nm with acceptable properties both in vitro and in vivo. The apoptosis study showed significant death of MDA-MB-231 cells after 24 h treatment with the prepared NPs. The real-time PCR study also demonstrated an almost complete shutdown of ROR1 expression. Guided by magnetic field, enhanced accumulation of NPs was observed in breast tumors induced by 4T1 cells in BALB/c mice. Histological evaluation of the tumor exhibited necrosis 14 days post-treatment with the siRNA-loaded NPs; whereas, the untreated tumor was proliferating. Also, the tumor growth rate was significantly decreased after treatment with siRNA-loaded NPs in vivo. In conclusion, the prepared delivery system could be considered as a potential therapeutic strategy for treating TNBC.

Trimethyl-Chitosan Coated Gold Nanoparticles Enhance Delivery, Cellular Uptake and Gene Silencing Effect of EGFR-siRNA in Breast Cancer Cells.

Purpose: Despite the promising therapeutic effects of gene silencing with small interfering RNAs (siRNAs), the challenges associated with delivery of siRNAs to the tumor cells in vivo, has greatly limited its clinical application. To overcome these challenges, we employed gold nanoparticles modified with trimethyl chitosan (TMC) as an effective delivery carrier to improve the stability and cellular uptake of siRNAs against epidermal growth factor receptor (EGFR) that is implicated in breast cancer. Methods: AuNPs were prepared by the simple aqueous reduction of chloroauric acid (HAuCl4) with ascorbic acid and coated with synthesized TMC. EGFR-siRNA was then complexed with the AuNPs-TMC via electrostatic interaction to make AuNPs-TMC/EGFR-siRNA with a w/w ratio of 10:1. Nanoparticles were assessed for physicochemical characteristics and in vitro cellular behavior on MCF-7 breast cancer cell line. Results: Spherical and positively charged AuNPs-TMC (67 nm, +45 mV) were successfully complexed with EGFR-siRNA (82 nm, +11 mV) which were able to retard the gene migration completely. Confocal microscopy and flow cytometry analysis demonstrated complete cellular uptake of Cy5 labeled AuNPs-TMC in the MCF-7 cells after 4 h incubation. MTT test after 48 h incubation showed that the AuNPs-TMC were safe but when combined with EGFR-siRNA exert significant cytotoxicity while the cell viability was about 50%. These nanocomplexes also showed a high gene expression knockdown (86%) of EGFR and also a high apoptosis rate (Q2 + Q3 = 18.5%) after 24 h incubation. Conclusion: This study suggests that the simply synthesized AuNPs-TMC are novel, effective, and promising nanocarriers for siRNA delivery, and AuNPs-TMC/EGFR-siRNA appears to be a potential therapeutic agent for breast cancer treatment.