A Novel Folic Acid Receptor-Targeted Drug Delivery System Based on Curcumin-Loaded β-Cyclodextrin Nanoparticles for Cancer Treatment

Abstract

Purpose A novel folate receptor-targeted β-cyclodextrin (β-CD) drug delivery vehicle was constructed to improve the bioavailability, biosafety, and drug loading capacity of curcumin. Controlled release and targeted delivery was achieved by modifying the nanoparticles with folic acid (FA). Methods Folate-conjugated β-CD-polycaprolactone block copolymers were synthesized and characterized. Curcumin-loaded nanoparticles (FA-Cur-NPs) were structured by self-assembly. The physicochemical properties, stability, release behavior and tumor-targeting ability of the fabricated nanoparticles were studied. Results The average particle size and drug loading of FA-Cur-NPs was 151.8 nm and 20.27%, respectively. Moreover, the FA-Cur-NPs exhibited good stability in vitro for 72 h. The drug release profiles showed that curcumin from FA-Cur-NPs was released significantly faster in a pH 6.4 phosphate buffered solution (PBS) than in pH 7.4, indicating that curcumin can be enriched around the tumor site compared with normal cells. Additionally, the internalization of FA-Cur-NPs was aided by FA receptor-mediated endocytosis, and its cytotoxicity was proportional to the cellular uptake efficiency. Furthermore, in vivo studies confirmed that FA-Cur-NPs exhibited marked accumulation in the tumor site and excellent antitumor activity. Conclusion These findings suggest that FA-Cur-NPs are a promising approach for improving cancer therapy through active targeting and controllable release.

Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability

“…Additionally, in vitro cytotoxicity was proportional to cellular uptake efficiency and the in vivo marked accumulation in tumor site was responsible of greater antitumor activity. These findings indicated FA-CUR-NPs could represent a promising approach for improving cancer therapy through active targeting and controllable release [226]. Moreover, in another work the use of hydroxypropyl-β-CD as a carrier-solubilizer improved solubility of the curcumin-piperine system, its permeability through biological membranes (gastrointestinal tract, blood-brain barrier), the antioxidant and antimicrobial activities and as well as the enzymatic inhibition against acetylcholinesterase and butyrylcholinesterase [227].…”

“…Recently, a nano-drug system namely FA-CUR-NPs consisting of FA, β-CD, εCL and curcumin was performed to improve curcumin delivery in cervical cancer tissues which overexpress FRs and to achieve controllable release in vitro and in vivo. In this system, FA binding to FRs was used as a targeting molecule, β-CD modified by ε-CL as delivery carrier and for controlling drug release and curcumin as a model drug to limit multidrug resistance after administration [226]. The study demonstrated that in vitro curcumin release rate from FA-CUR-NPs under tumor microenvironment conditions (pH 6.4), was three times faster than that under systemic circulation conditions (pH 7.4).…”

“…β-CD + CUR Superior sunlight stability and solubility respect to pure colourant [218] Liquid-type β-CD + CUR Improved solubility in water and bioavailability [220,221] Solid type β-CD + CUR Improved storage stability and biovailability [222] CUR-CD-CS Superior solubility, cellular absorption and antitumor effects compared to free curcumin in skin cancer cells [223] β-CD + CUR Improved uptake and therapeutic efficacy in prostate cancer cells [154] β-CD + CUR Improved delivery and therapeutic efficacy compared to free curcumin in both in vitro lung carcinoma cell lines and in vivo mouse hepatoma xenograft models [224] β-CD + CUR Superior anticancer effects respect to free curcumin in cervical cancer cells [225] FA-CUR-NPs Improved drug release rate, cellular uptake efficiency and in vitro and in vivo antitumor activity respect to free curcumin in cervical cancer cells [226] Hydroxypropyl-β-CD+ CUR+piperine Improved solubility of the curcumin-piperine system, its permeability through biological membranes, antioxidant and antimicrobial activities and enzymatic inhibition [227] SDs (with Gelucire ® 50/13-Aerosil) + CUR Improved stability, water solubility, dissolution rate, bioavailability and anti-inflammatory activity in rats [229] Solutol ® HS15 SDs + CUR Improved solubility and bioavailability compared to free curcumin [231] SDs (with cellulose acetate and mannitol) + CUR Improved water solubility and oral bioavailability compared to free curcumin [232] SDs + CUR Superior water solubility and gastrointestinal absorption in rats [233] SDs (with Poloxamer 407) + CUR Improved water dispersibility and cytotoxic effects against breast, lung, cervical and hepatocellular cancer cells [234] Curcumin Conjugates Formulations Piperine + CUR Curcumin enhanced serum levels, reduced elimination half-life and clearance, increased bioavailability in rats and humans [236] Piperine + CUR Curcumin increased bioavailability in epileptic rats [237] Piperine + CUR Curcumin enhanced intestinal absorption and bioavailability in rats [238] BCM-95CG (Biocurcumax ® ): piperine + lecithin + CUR Curcumin improved bioavailability and pharmacokinetic profile respect to free drug in healthy subjects [239]…”

Nanoparticles in Cancer Treatment: A Narrative Review

“…The active targeting mode of nanoparticles depends upon the utilization of certain ligands like folate and transferrin, which bind to the proteins that are over-expressed or somewhat expressed on the target cellular sites [57]. This instigates the inbound folding of membranes and incorporates the nanoparticles into the cells through a phenomenon named receptor-mediated endocytosis (Figure 3).…”

Preparation of Curcumin-Eudragit® E PO Solid Dispersions with Gradient Temperature through Hot-Melt Extrusion

“…However, its therapeutic efficacy is limited because of its poor solubility [ 5 ]. Several methods, such as the preparation of liposomes and nanoparticles [ 6 , 7 ] and self-microemulsion, have been used to increase the solubility and dissolution rate of insoluble drugs [ 8 , 9 , 10 , 11 ]. Solid dispersion (SD) can also efficiently increase the dissolution rate and solubility of insoluble drugs by changing the size and dispersion within the carrier.…”