Fabrication and characterization of microstructured and pH sensitive interpenetrating networks hydrogel films and application in drug delivery field

Novel microstructured and pH sensitive poly(acryliac acid-co-2-hydroxyethyl methacrylate)/poly(vinyl alcohol) (P(AA-co-HEMA)/PVA) interpenetrating network (IPN) hydrogel films were prepared by radical precipitation copolymerization and sequential IPN technology. The first P(AA-co-HEMA) network was synthesized in the present of IPN aqueous solution by radical initiating, then followed by condensation reaction (Glutaraldehyde as crosslinking agent) within the resultant latex, it formed multiple IPN microstructured hydrogel film. The film samples were characterized by IR, SEM and DSC. Swelling and deswelling behaviors and mechanical property showed the novel multiple IPN nanostuctured film had rapid response and good mechanical property. The IPN films were studied as controlled drug delivery material in different pH buffer solution using cationic compound, crystal violet as a model drug.

A magnetic, luminescent and mesoporous core-shell structured composite material as drug carrier

In this paper, hydrothermal synthesized Fe3O4 microspheres have been encapsulated with nonporous silica and a further layer of ordered mesoporous silica through a simple sol-gel process. The surface of the outer silica shell was further functionalized by the deposition of YVO4:Eu3+ phosphors, realizing a sandwich structured material with mesoporous, magnetic and luminescent properties. The multifunctional system was used as drug carrier to investigate the storage and release properties using ibuprofen (IBU) as model drug by the surface modification. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectra (XPS), Fourier transform infrared spectroscopy (FT-IR), N-2 adsorption/desorption, photoluminescence (PL) spectra, and superconducting quantum interference device (SQUID) were used to characterized the samples.

Multifunctional Hydroxyapatite Nanofibers and Microbelts as Drug Carriers

Luminescent, mesoporous, and bioactive europium-doped hydroxyapatite (HAp:Eu3+) nanofibers and microbelts have been prepared by a combination of sol-gel and electrospinning processes with a cationic surfactant as template. The obtained multifunctional hydroxyapatite nanofibers and microbelts, which have mesoporous structure and red luminescence, were tested as drug carriers by investigating their drug-storage/release properties with ibuprofen (IBU) as model drug. X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution (HR) TEM, FTIR spectroscopy, N-2 adsorption/desorption, photoluminescence (PL) spectra, and UV/Vis spectroscopy were used to characterize the structural, morphological, textural, and optical properties of the resulting samples.

Luminescent and Mesoporous Europium-Doped Bioactive Glasses (MBG) as a Drug Carrier

Luminescent and mesoporous europium-doped bioactive glasses (MBG:Eu) were successfully synthesized by a two-step acid-catalyzed self-assembly process combined with hydrothermal treatment in an inorganic-organic system. The obtained MBG was performed as a drug delivery carrier to investigate the drug storage/release properties using ibuprofen (IBU) as a model drug. The structural, morphological, textural and optical properties were well characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N-2 adsorption/desorption, and photoluminescence (PL) spectra, respectively. The results reveal that the MBG exhibit the typical ordered characteristics of the hexagonal mesostructure. This composite shows sustained release profile with ibuprofen as the model drug. The IBU-loaded samples still show red luminescence of Eu3+ (D-5(0)-F-7(1, 2)) under UV irradiation, and the emission intensities of Eu3+ in the drug carrier system vary with the released amount of IBU, thus making the drug release be easily tracked and monitored by the change of the luminescence intensity.

Magnetic Mesoporous Silica Spheres for Drug Targeting and Controlled Release

Magnetically functionalized mesoporous silica spheres with different size (average diameter, A.D.) from 150 nm to 2 mu m and pore size distribution were synthesized by generating magnetic FexOy nanoparticles onto the mesoporous silica hosts using the sol-gel method. The X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), N-2 adsorption/desorption results show that these composites conserved regular sphere morphology and ordered mesoporous structure after the formation of FexOy nanoparticles. XRD and X-ray photoelectron spectroscopy (XPS) analysis confirmed that the FexOy generated in these mesoporous silica hosts is mainly composed of gamma-Fe2O3. Magnetic measurements reveal that these composites with different gamma-Fe2O3 loading amounts possess super-paramagnetic properties at 300 K, and the saturation magnetization increases with increasing Fe ratio loaded.

Synthesis and characterization of magnetic FexOy@SBA-15 composites with different morphologies for controlled drug release and targeting

Magnetic functionalization of the ordered mesoporous SBA-15 (SiO2) aggregate blocks and rice grain-like particles were realized by using a sol-gel method, resulting in the formation of FexOy@SBA-15 composite materials. The X-ray diffraction (XRD), N-2 adsorption/desorption, and transmission electron microscopy (TEM) results show that these composites conserved ordered mesoporous structure after the formation of FexOy nanoparticles in the pores and on the outer surface of SBA-15. It was confirmed by the XRD and X-ray photoelectron spectroscopy (XPS) analysis that the FexOy generated in these mesoporous silica hosts is mainly composed of gamma-Fe2O3. Magnetic measurements reveal that these composites possess superparamagnetic properties at 300 K. The saturation magnetization of these composites increased with the increasing loading amount of gamma-Fe2O3. These composites, which possess high surface area and high pore volume, show magnetic response sufficient for drug targeting in the presence of an external magnetic field.

Monodisperse mesoporous superparamagnetic single-crystal magnetite nanoparticles for drug delivery

In this contribution, we report a facile, gram-scale, low-cost route to prepare monodisperse superparamagnetic single-crystal magnetite NPs with mesoporous structure (MSSMN) via a very simple solvothermal method. The formation mechanism of MSSMN is also discussed and we think that Ostwald ripening probably plays an important role in this synthesis process. It is also interestingly found that the size and morphology of mesoporous Fe3O4 NPs can be easily controlled by changing the amount of NaOH and 1,2-ethylenediamine (ETH). Most importantly, the MSSMN can be used as an effective drug delivery carrier. A typical anticancer drug, doxorubicin (Dox), is used for drug loading, and the release behaviors of Dox in two different pH solutions are studied. The results indicate that the MSSMN has a high drug loading capacity and favorable release property for Dox; thus, it is very promising for the application in drug delivery.

Anticancer Drug-DNA Interactions Measured Using a Photoinduced Electron-Transfer Mechanism Based on Luminescent Quantum Dots

A sensing system based on the photoinduced electron transfer of quantum dots (QDs) was designed to measure the interaction of anticancer drug and DNA, taking mitoxantrone (MTX) as a model drug. MTX adsorbed on the surface of QDs can quench the photoluminescence (PL) of QDs through the photoinduced electron-transfer process; and then the addition of DNA will bring the restoration of QDs PL intensity, as DNA can bind with MTX and remove it from QDs. Sensitive detection of MTX with the detection limit of 10 nmol L-1 and a linear detection range from 10 nmol L-1 to 4.5 mu mol L-1 was achieved. The dependence of PL intensity on DNA amount was successfully utilized to investigate the interactions between MTX and DNA. Both the binding constants and the sizes of binding site of MTX-DNA interactions were calculated based on the equations deduced for the PL recovery process. The binding constant obtained in our experiment was generally consistent with previous reports. The sensitive and speedy detection of MTX as well as the avoidance of modification or immobilization process made this system suitable and promising in the drug-DNA interaction studies.

A Novel Biodegradable and Light-Breakable Diblock Copolymer Micelle for Drug Delivery

A facile approach to the preparation of light-responsive copolymer micelles is developed. This approach is based on the attachment of hydrophobic groups to one block of a diblock copolymer via a light-sensitive linkage. The micelles can be dissociated under light irradiation and release the encapsulated pyrene. The obtained polymeric micelles are expected to be of use as drug-delivery vehicles.

Ultrafine PEG-PLA fibers loaded with both paclitaxel and doxorubicin hydrochloride and their in vitro cytotoxicity

By means of "emulsion-electrospinning", both hydrophobic and hydrophilic drugs, paclitaxel (PTX) and doxorubicin hydrochloride (DOX), were successfully loaded into PEG-PLA nanofiber mats to realize multi-drug delivery. The release behaviors of both the drugs from the same fiber mats were ascribed to their solubility properties and distribution status in the fibers. Due to its high hydrophilicity, DOX was easy to diffuse out from the fibers, and its release rate was always faster than that of hydrophobic PTX. Moreover, the release rate of PTX was accelerated by DOX's release from the same drug-loaded fibers. In vitro cytotoxicity against rat Glioma C6 cells indicated that the dual drug combination showed a higher inhibition and apoptosis against C6 cells than a single drug-loaded system, which suggests the promise for multi-drug delivery on combination therapy.

Synthesis of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Novel intelligent hydrogels composed of biodegradable and pH-sensitive poly(L-glutamic acid) (PGA) and temperature sensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNH) were synthesized and characterized for controlled release of hydrophilic drug. The influence of pH on the equilibrium swelling ratios of the hydrogels was investigated. A higher PNH content resulted in lower equilibrium swelling ratios. Although temperature had little influence on the swelling behaviors of the hydrogels, the changes of optical transmittance of hydrogels as a function of temperature were marked, which showed that the PNH part of hydrogel exhibited hydrophobic property at temperature above the lower critical solution temperature (LCST). The biodegradation rate of the stimuli-sensitive hydrogels in the presence of enzyme was directly proportional to the PGA content. Lysozyme was chosen as a model drug and loaded into the hydrogels.

Glycyrrhetinic acid-modified nanoparticles for drug delivery: Preparation and characterization

In this work, glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) used as liver targeted carrier for drug delivery, was prepared via hemisuccinate as a bridged group. The structure of the product was confirmed by IR and NMR methods and the degree of substitution (DS) of glycyrrhetinic acid groups was estimated via elemental analysis. Nanoparticles were formed by ionic gelation methold. The drug-loading and release behavior of the nanoparticles were investigated using BSA as the model drug. The results indicated that the carrier with a highest DS of 5.19% could be got and the DS was controlled by changing reaction temperature or feed ratio. BSA could be entrapped into the nanoparticles with the drug-loading ratio of 26.3% and the encapsulation efficiency of 81.5%. A sustained release over an 11-day period was observed in pH 7.4 in vitro.

Biodegradable amphiphilic polymer-drug conjugate micelles

The coupling of drugs to macromolecular carriers received an important impetus from Ringsdorf's notion of polymer-drug conjugates. Several water-soluble polymers, poly(ethylene glycol), poly[N-(2-hydroxypropyl) methacrylamidel, poly(L-glutamic acid) and dextran, are studied intensively and have been utilized successfully in clinical research. The promising results arising from clinical trials with polymer-drug conjugates (e.g., paclitaxel, doxorubicin, camptothecins) have provided a firm foundation for other synthetic polymers, especially biodegradable polymers, used as drug delivery vehicles. This review discusses biodegradable polymeric micelles as an alternative drug-conjugate system. Particular focus is on A-B or B-A-B type biodegradable amphiphilic block copolymer such as polylactide, morpholine-2,5-dione derivatives and cyclic carbonates, which can form a core-shell micellar structure, with the hydrophobic drug-binding segment forming the hydrophobic core and the hydrophilic segment as a hydrated outer shell. Polymeric micelles can be designed to avoid uptake by cells of reticuloendothelial system and thus enhance their blood lifetime via the enhanced permeability and retention effect.

Quantifying intrinsic specificity: A potential complement to affinity in drug screening

We report here the investigation of a novel description of specificity in protein-ligand binding based on energy landscape theory. We define a new term, intrinsic specificity ratio (ISR), which describes the level of discrimination in binding free energies of the native basin for a protein-ligand complex from the weaker binding states of the same ligand. We discuss the relationship between the intrinsic specificity we defined here and the conventional definition of specificity. In a docking study of molecules with the enzyme COX-2, we demonstrate a statistical correspondence between ISR value and geometrical shapes of the small molecules binding to COX-2. We further observe that the known selective (nonselective) inhibitors of COX-2 have higher (lower) ISR values. We suggest that intrinsic specificity ratio may be a useful new criterion and a complement to affinity in drug screening and in searching for potential drug lead compounds.

Luminescence functionalization of SBA-15 by YVO4 : Eu3+ as a novel drug delivery system

Luminescence functionalization of the ordered mesoporous SBA-15 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process, resulting in the formation of the YVO4:Eu3+@SBA-15 composite material. This material, which combines the mesoporous structure of SBA-15 and the strong red luminescence property of YVO4:Eu3+, can be used as a novel functional drug delivery system. The structure, morphology, porosity, and optical properties of the materials were well characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, N-2 adsorption, and photoluminescence spectra. As expected, the pore volume, surface area, and pore size of SBA-15 decrease in sequence after deposition of the YVO4:Eu3+ layer and the adsorption of ibuprofen (IBU, drug). The IBU-loaded YVO4:Eu3+@SBA-15 system still shows the red emission of Eu3+ (617 nm, D-5(0)-F-7(2)) under UV irradiation and the controlled drug release property. Additionally, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU in the system, making the extent of drug release easily identifiable, trackable, and monitorable by the change of luminescence. The system has great potential in the drug delivery and disease therapy fields.