Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate

Abstract

Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH), based on a low-molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In order to enhance the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was mixed with HA-PBCA during the preparation process. The MH-loaded HA-PBCA “plain” nanoparticle (MH-PNs) and HA-PBCA/TPGS “mixed” nanoparticles (MH-MNs) were concomitantly characterized in terms of loading efficiency, particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MH-PNs and MH-MNs exhibited a spherical morphology with a negative zeta potential and a particle size less than 200 nm, favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase in drug-loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of MH in A549 cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibited selective cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition, the cellular uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A549 cells. The CD44 receptor competitive inhibition and the internalization pathway studies suggested that the internalization mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dependent endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and induced more tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearing mice. Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted delivery of lipophilic anticancer drugs.

Drug Delivery Innovations for Enhancing the Anticancer Potential of Vitamin E Isoforms and Their Derivatives

“…The N-DOX-TOS nanoparticles significantly reduced the growth of MCF-7 cells and induced a higher delay in tumor growth in CT26-tumor-bearing mice compared to the control group [ 128 ]. In support of the specific anticancer properties of TPGS, a recent study revealed that blank TPGS nanoparticles showed toxicity against A549 lung cancer cells without harming normal cells [ 129 ]. In a nanoparticle formulation, TPGS further enhanced the toxicity of Morin Hydrate (MH), a naturally occurring bioflavonoid, against A549 cells both in vitro and in vivo [ 129 ].…”

“…In support of the specific anticancer properties of TPGS, a recent study revealed that blank TPGS nanoparticles showed toxicity against A549 lung cancer cells without harming normal cells [ 129 ]. In a nanoparticle formulation, TPGS further enhanced the toxicity of Morin Hydrate (MH), a naturally occurring bioflavonoid, against A549 cells both in vitro and in vivo [ 129 ].…”

Tumor-targeting templated silica nanoparticles as a dual-drug delivery system for anti-angiogenic ovarian cancer therapy

“…To evaluate the cellular uptake of Tra/CD/SLNs and HA/Tra/CD/SLNs in a SKOV3 cell line (Cell Bank of Shanghai Institute of Biochemistry and Cell Biology; Chinese Academy of Sciences, Shanghai, China), fluorescent C6 was encapsulated in the nanoparticles ( 14 ) via the same method used for CD loading. SKOV3 cells were seeded in confocal dishes (Φ=15 mm) at a density of 1×10 5 cells/dish and cultured overnight (humidified atmosphere containing 5% CO 2 at 37°C).…”

“…In previous decades, DDSs equipped with tumor-targeting ligands and specific tumor-homing properties have been identified as a favorable way to avoid unwanted side effects. These desired properties have paved the way for the development of multiple DDSs ( 14 – 16 ). As a widely-adopted targeting ligand, hyaluronic acid (HA) has been demonstrated in a previous study to be a safe and effective material that may be easily modified and applied to multiple other materials ( 17 ).…”

Silica nanoparticle-based dual-responsive nanoprodrug system for liver cancer therapy

“…A large proportion of the most commonly applied anti-cancer drugs are hydrophobic and have numerous disadvantages, including low solubility and stability as well as severe side effects, which have greatly limited their clinical applications. To solve this dilemma, a wide range of well-designed nanocarriers have been developed with the aim to improve the anti-cancer efficacy of hydrophobic anti-cancer drugs by employing various materials ranging from organic to inorganic ones ( 1 – 5 ). Paclitaxel (PTX) has long been identified as a broad-spectrum anti-cancer drug with higher effectiveness than its competitors; therefore, a variety of PTX formulations have been explored seeking to employ the advantages of PTX while overcoming its disadvantages ( 6 – 8 ).…”