Near‐Infrared‐Controlled,Targeted Hydrophobic Drug‐Delivery System for Synergistic Cancer Therapy

Hydrophobicity has been an obstacle that hinders the use of many anticancer drugs. A critical challenge for cancer therapy concerns the limited availability of effective biocompatible delivery systems for most hydrophobic therapeutic anticancer drugs. In this study, we have developed a targeted near‐infrared (NIR)‐regulated hydrophobic drug‐delivery platform based on gold nanorods incorporated within a mesoporous silica framework (AuMPs). Upon application of NIR light, the photothermal effect of the gold nanorods leads to a rapid rise in the local temperature, thus resulting in the release of the entrapped drug molecules. By integrating chemotherapy and photothermotherapy into one system, we have studied the therapeutic effects of camptothecin‐loaded AuMP‐polyethylene glycol‐folic acid nanocarrier. Results revealed a synergistic effect in vitro and in vivo, which would make it possible to enhance the therapeutic effect of hydrophobic drugs and decrease drug side effects. Studies have shown the feasibility of using this nanocarrier as a targeted and noninvasive remote‐controlled hydrophobic drug‐delivery system with high spatial/temperal resolution. Owing to these advantages, we envision that this NIR‐controlled, targeted drug‐delivery method would promote the development of high‐performance hydrophobic anticancer drug‐delivery system in future clinical applications.     

Design and Synthesis of Lipidic Organoalkoxysilanes for the Self‐Assembly of Liposomal Nanohybrid Cerasomes with Controlled Drug Release Properties

This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water‐soluble doxorubicin (DOX) and water‐insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome‐forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug‐loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome‐forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes.     

Enzyme‐Responsive Silica Mesoporous Supports Capped with Azopyridinium Salts for Controlled Delivery Applications

The preparation of a new capped silica mesoporous material, Rh‐Azo‐S , for on‐command delivery applications in the presence of target enzymes is described. The material consists of nanometric mesoporous MCM‐41‐like supports loaded with Rhodamine B and capped with an azopyridine derivative. The material was designed to show “zero delivery” and to display a cargo release in the presence of reductases and esterases, which are usually present in the colon, mainly due to intestinal microflora. The opening and cargo release of Rh‐Azo‐S in vitro studies were assessed and seen to occur in the presence of these enzymes, whereas no delivery was noted in the presence of pepsine. Moreover, Rh‐Azo‐S nanoparticles were used to study controlled Rhodamine B dye delivery in intracellular media. HeLa cells were employed for testing the “non”‐toxicity of nanoparticles. Moreover, delivery of the dye in these cells, through internalization and enzyme‐mediated gate opening, was confirmed by confocal microscopy. Furthermore, the nanoparticles capped with the Azo group and loaded with a cytotoxic camptothecin ( CPT ) were also prepared (solid CPT‐Azo‐S ) and used as delivery nanodevices in HeLa cells. When this solid was employed, the cell viability decreased significantly due to internalization of the nanoparticles and delivery of the cytotoxic agent.     

Integrated Hollow Mesoporous Silica Nanoparticles for Target Drug/siRNA Co‐Delivery

A hollow mesoporous silica nanoparticle (HMSNP) based drug/siRNA co‐delivery system was designed and fabricated, aiming at overcoming multidrug resistance (MDR) in cancer cells for targeted cancer therapy. The as‐prepared HMSNPs have perpendicular nanochannels connecting to the internal hollow cores, thereby facilitating drug loading and release. The extra volume of the hollow core enhances the drug loading capacity by two folds as compared with conventional mesoporous silica nanoparticles (MSNPs). Folic acid conjugated polyethyleneimine (PEI‐FA) was coated on the HMSNP surfaces under neutral conditions through electrostatic interactions between the partially charged amino groups of PEI‐FA and the phosphate groups on the HMSNP surfaces, blocking the mesopores and preventing the loaded drugs from leakage. Folic acid acts as the targeting ligand that enables the co‐delivery system to selectively bind with and enter into the target cancer cells. PEI‐FA‐coated HMSNPs show enhanced siRNA binding capability on account of electrostatic interactions between the amino groups of PEI‐FA and siRNA, as compared with that of MSNPs. The electrostatic interactions provide the feasibility of pH‐controlled release. In vitro pH‐responsive drug/siRNA co‐delivery experiments were conducted on HeLa cell lines with high folic acid receptor expression and MCF‐7 cell lines with low folic acid receptor expression for comparison, showing effective target delivery to the HeLa cells through folic acid receptor meditated cellular endocytosis. The pH‐responsive intracellular drug/siRNA release greatly minimizes the prerelease and possible side effects of the delivery system. By simultaneously delivering both doxorubicin (Dox) and siRNA against the Bcl‐2 protein into the HeLa cells, the expression of the anti‐apoptotic protein Bcl‐2 was successfully suppressed, leading to an enhanced therapeutic efficacy. Thus, the present multifunctional nanoparticles show promising potentials for controlled and targeted drug and gene co‐delivery in cancer treatment.     

Intramolecular aglycon delivery for (1 → 2)-β-mannosylation: towards the synthesis of phospholipomannan of Candida albicans

A high yielding method for 1,2-cis-β-D-mannosylation by intra-molecular aglycon delivery (IAD) through p-methoxy benzyl ether/acetal exchange and phenylsulfoxide donor is reported, along with its application in iterative assembly of antigenic (1 → 2)-β-pentamannoside domain of phospholipomannan (PLM) of fungal pathogen Candida albicans.     

Quality by Design Approach for Development of W/O Type Microemulsion-Based Transdermal Systems for Atenolol

The objective of the present investigation was to develop microemulsion-based transdermal systems of highly water soluble drug, Atenolol, by quality by design technique. Atenolol-loaded W/O microemulsions were optimized using D-optimal design with concentrations of oil, surfactants mixture, and water as independent variables, which was converted into microemulsion-based gel (MBG). The results of in vitro permeation of the optimized batch of Atenolol-loaded MBG revealed significant increase in permeability parameters as compared to its convention gel. All results suggested suitability of W/O type MEs as carriers for transdermal delivery of highly water soluble drug, Atenolol.     

Water-dispersible non-aqueous emulsions stabilized by a poly(butadiene)-b-poly(2-vinylpyridine) block copolymer

Submicron non-aqueous emulsions, of interest for biomedical and cosmetic formulations, were developed for the system comprising poly(ethylene glycol) (PEG) 400 and Miglyol 812, an enzymatic degradable liquid glycerine ester. These emulsions, with PEG 400 as continuous phase and Miglyol 812 droplets, in the size range of 200 nm, were stabilized by a poly(butadiene)-b-poly(2-vinylpyridine) (PBut-b-P2VP) block copolymer with a composition close to 50/50 wt%. The droplet size, stability and the rheological characteristics were examined as a function of the copolymer concentration. An original aspect of these anhydrous emulsions, with a water miscible continuous phase, is their water dispersibility without additional surfactant. In fact, the initial anhydrous emulsion is sterically stabilized and after water addition at low pH, the protonated P2VP sequence of the copolymer provides the electro-steric stabilization. This oil-in-water emulsion is characterized by sub micron sized Miglyol 812 droplets in an aqueous phase of PEG 400 and water at pH 1.