Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy

Abstract

Resveratrol (RES) is a naturally existing polyphenol which exhibits anti-oxidant, anti-inflammatory, and anti-cancer properties. In recent years, RES has attracted attention for its synergistic effect with other anti-cancer drugs for the treatment of drug resistant cancers. However, RES faces the issues of poor pharmacokinetics, stability and low solubility which limits its clinical application. In present study, RES has been loaded onto uniformly sized (~60 nm) mesoporous silica nanoparticles (MSNs) to improve its in vitro anti-proliferative activity and sensitization of Docatexal in hypoxia induced drug resistance in prostate cancer. RES was efficiently encapsulated within phosphonate (negatively charged) and amine (positively charged) modified MSNs. The effect of surface functionalization was studied on the loading, in vitro release, anti-proliferative and cytotoxic potential of RES using prostate cancer cell line. At pH 7.4 both free and NH2-MSNs loaded RES showed burst release which was plateaued with almost 90% of drug released in first 12 h. On the other hand, PO3-MSNs showed significantly slower release kinetics with only 50% drug release in first 12 h at pH 7.4. At pH 5.5, however, both the PO3-MSNs and NH2-MSNs showed significant control over release (around 40% less release compared with free RES in 24 h). Phosphonate modified MSNs significantly enhanced the anti-proliferative potential of RES with an IC50 of 7.15 μM as compared to 14.86 μM of free RES whereas amine modified MSNs didn't affect proliferation with an IC50 value higher than free RES (20.45 μM). Furthermore, RES loaded onto PO3-MSNs showed robust and dose dependent sensitization of Docatexal in hypoxic cell environment which was comparable to pure RES solution. This study provides an example of applicability of MSNs loaded with polyphenols such as RES as next generation anticancer formulations for treating drug resistant cancers such as prostate cancer.

Resveratrol Nanoparticles: A Promising Therapeutic Advancement over Native Resveratrol

“…The sizes of the MSNs thus prepared were uniform with approx. The diameter of 72 nm after modifications [168]. The zeta potential of the RES-loaded and functional group modified MSNs were in the range of −42.8 and −11.2 mV, indicating the non-aggregation in preparation.…”

“…In the development of a nano-delivery vehicle for RES, mesoporous silica nanoparticles (MSNs) has been advocated for its silanol functional groups on its surface for modification of the surface [167,168], improved pore size, and particle size, and is used in for encapsulation of hydrophilic and hydrophobic molecules. The fabricated nanoparticles of MSNs have positively charged surface amine groups and negatively charged phosphonate groups and are loaded with RES to effectively act against those cancer cells that are found resistant to Doc in PC3 cells.…”

“…A combination of (0.1-10 nM) Doc of Doc and (10 µM) RES would be effective in exerting toxic reactions in PC3 cells without affecting the normal cells. This is made possible with the increased anti-oxidant potential of RES in scavenging the ROS that is generated under hypoxic conditions [168]. Hence, RES encapsulated in PO3-MSN nanoparticles are a promising tool for providing an alternative to chemotherapy resistant-prostate cancer.…”

Evaluation of the Solid Dispersion System Engineered from Mesoporous Silica and Polymers for the Poorly Water Soluble Drug Indomethacin: In Vitro and In Vivo

“…The MSNs were synthesized according to a previously reported method [16]. In brief, the MSNs were synthesized by mixing 380 mL of NaOH solution (0.5 mg/mL) and 100 mL of CTAB solution.…”

Resveratrol Induces the Osteogenic Differentiation via MiR-320c by Targeting Runx2 and Is Involved in the Adipogenic differentiation of BMSCs

“…In recent studies, a few researchers focused on the naturally occurring polyphenolic compound, resveratrol (3,4,5-trihydroxystilbene) (RSVL), which was found in red wine and some Asian medicinal herbs [7]. It has been reported that RSVL exhibits the anti-oxidation, anti-in ammatory anti-aging and anticancer functions [8][9][10]. Besides, previous studies showed that RSVL could attenuate the bone loss in ovariectomy-induced osteoporosis and promote the proliferation and osteogenic differentiation of mesenchymal stem cells [11][12][13].…”