Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells

Abstract

Renal Cell Carcinoma (RCC) often becomes resistant to targeted therapies, and in addition, dose-dependent toxicities limit the effectiveness of therapeutic agents. Therefore, identifying novel drug delivery approaches to achieve optimal dosing of therapeutic agents can be beneficial in managing toxicities and to attain optimal therapeutic effects. Previously, we have demonstrated that Honokiol, a natural compound with potent anti-tumorigenic and anti-inflammatory effects, can induce cancer cell apoptosis and inhibit the growth of renal tumors in vivo. In cancer treatment, implant-based drug delivery systems can be used for gradual and sustained delivery of therapeutic agents like Honokiol to minimize systemic toxicity. Electrospun polymeric fibrous scaffolds are ideal candidates to be used as drug implants due to their favorable morphological properties such as high surface to volume ratio, flexibility and ease of fabrication. In this study, we fabricated Honokiol-loaded Poly(lactide-co-glycolide) (PLGA) electrospun scaffolds; and evaluated their structural characterization and biological activity. Proton nuclear magnetic resonance data proved the existence of Honokiol in the drug loaded polymeric scaffolds. The release kinetics showed that only 24% of the loaded Honokiol were released in 24hr, suggesting that sustained delivery of Honokiol is feasible. We calculated the cumulative concentration of the Honokiol released from the scaffold in 24hr; and the extent of renal cancer cell apoptosis induced with the released Honokiol is similar to an equivalent concentration of direct application of Honokiol. Also, Honokiol-loaded scaffolds placed directly in renal cell culture inhibited renal cancer cell proliferation and migration. Together, we demonstrate that Honokiol delivered through electrospun PLGA-based scaffolds is effective in inhibiting the growth of renal cancer cells; and our data necessitates further in vivo studies to explore the potential of sustained release of therapeutic agents-loaded electrospun scaffolds in the treatment of RCC and other cancer types.

Regulation of the PTEN/PI3K/AKT pathway in RCC using the active compounds of natural products in vitro

“…Compared with synthetic drugs, treatment with natural products have fewer side effects, while exhibiting favorable outcomes ( 13 ). Although other studies have reported that several natural products, such as Epigallocatechin Gallate ( 19 ), quercetin ( 20 ), englerin A ( 21 ), honokiol ( 22 ), curcumin ( 23 ) and resveratrol ( 24 ) have shown beneficial results in preclinical studies of RCC, the research on the mechanism of the therapeutic activities of natural products on RCC is remains limited. The present study examined the antitumor effects of natural products on RCC.…”

Multiple Cell Cultures for MRI Analysis

“…On the other hand, Hamedani et al, in their work, presented an innovative PLGA-based electrospun polymer fiber scaffold for renal cell carcinoma (RCC). The scaffold was loaded with a natural compound showing a strong anticancer and anti-inflammatory effect, which is Honokiol, which showed an inhibitory effect on the proliferation and migration of kidney cancer cells [ 152 ]. In turn, Zheng et al, in the latest research, presented the 3D scaffold HA15 bone tissue, printed in 3D β-TCP/PLGA technology with the drug promoting osteogenesis HA15 in in vivo studies in rabbits.…”

Stability of soluble honokiol loaded PLGA-PEG nanoparticles under normal and accelerated-aging conditions

“…In vivo and in vitro studies have also demonstrated anti-tumour effects of honokiol in a variety of cancers, including those of brain, blood, bone, skin, lung, colon, pancreas, breast, and prostate [4]. Specifically, honokiol activates cell cycle arrest and apoptosis, as well as inhibits proteins that promote cancer growth [4,5]. However, two connected phenyl rings in the chemical structure of honokiol cause its poor water solubility and limited bioavailability as well as instability due to the possibility of hydrolysis and oxidation [1,6].…”