Controlled Drug Release Applications Research Articles

Microwave-assisted synthesis of alginate-g-polyvinylpyrrolidone copolymer and its application in controlled drug release

The aim of this study is to synthesize graft copolymer (NaAlg-g-PVP) in microwave oven and prepare pH-responsive beads with high entrapment efficiency. For this purpose, PVP was grafted onto sodium alginate using microwave radiation. The copolymer obtained was characterized using FTIR, 1H-NMR, elemental analysis and thermogravimetric analysis. A series of NaAlg-g-PVP beads were prepared as drug delivery matrices for ibuprofen (IB) by cross-linking into beads via glutaraldehyde. The chemical stability of IB after encapsulation into beads was confirmed by FTIR, DSC, and X-RD analysis. Synthesis conditions of beads were optimized by considering entrapment efficiency, particle size, swelling capacity and their release data. Effects of such variables as graft yield and drug/polymer ratio were investigated at 1.2 and 7.4 pH values. Increasing the drug/polymer ratio and extent of cross-linking caused decrease in the IB release. On the other hand, increase in the graft yield led to increase in the IB release as well. The results also showed that NaAlg-g-PVP beads were positive pH-responsive.

Chitosan/pectin/gum Arabic polyelectrolyte complex: Process-dependent appearance, microstructure analysis and its application

Novel chitosan/pectin/gum Arabic polyelectrolyte complex (PEC) solutions and membranes with various compositions were prepared for biomedical applications. The appearance of the PEC solutions, either clear or turbid, was process-dependent and depended on how the three components were dissolved and mixed. The addition of gum Arabic to the chitosan and pectin significantly decreased the viscosities of the resultant PEC solutions due to the formation of globe-like microstructures that was accompanied by network-like microstructures and other molecular entanglements. The mechanical strength and hydrophilicity of the PEC membranes manufactured from the PEC solutions, especially for a weight ratio of 84/8/8 (chitosan/pectin/gum Arabic), were enhanced compared to pure chitosan membranes. Moreover, the use of the 84/8/8 PEC membranes as a drug carrier exhibited steady and fairly complete release of a drug (insulin) for 6h. Based on these promising results, the chitosan/pectin/gum Arabic PEC membranes have great potential in controlled drug release applications.

Preparation and Characterization of Poly (D,L-Lactide-co-Glycolide) (PLGA) Nanoparticles Loaded with Linamarin for Controlled Drug Release

Poly (D,L-lactide-co-glycolide) nanoparticles loaded with linamarin as a model drug were successfully prepared using the double emulsion solvent evaporation technique. The physicochemical characterization of the formulated nanoparticles revealed that they were spherical, nonaggregated, and negatively charged, with good drug encapsulation efficiencies (>50%) and average particle sizes <200 nm. Interestingly, all the nanoparticles exhibited dibasic release profiles with a starting burst release within the first 8 h, followed by a controlled release phase lasting four days. Thus, linamarin-loaded nanoparticles indicate a promising candidate for controlled drug release applications.

Cyclodextrin-Responsive Micelles Based on Poly(ethylene glycol)-Polypeptide Hybrid Copolymers as Drug Carriers.

Novel drug carriers based on poly(ethylene glycol) (PEG)-polypeptide copolymers, four-armed poly(ε-adamantane-l-lysine)2-block-poly(ethylene glycol)-block-poly(ε-adamantane-l-lysine)2 (PLys(Ad)2-b-PEG-b-PLys(Ad)2), have been prepared. The copolymers were synthesized via the ring-opening polymerization of amino acid N-carboxyanhydrides. The copolymers could spontaneously form core-shell micelles in aqueous solutions. It has been found that these micelles undergo triggered disassembly in response to an additional β-cyclodextrin (β-CD). The in vitro drug release in response to β-CD has been studied, and the result shows that the release of the entrapped drug doxorubicin (DOX) from the micelles could be accelerated by the addition of β-CD. Their cytotoxicity and cell internalization behavior were also investigated in detail. These micelles are expected to have great potential in controlled drug release applications.

Dissipative particle dynamics simulation of onion phase in star-block copolymer

A dissipative particle dynamics simulation technique was used to investigate the effect of molecular architecture of star-block copolymer on the patterned structure in a nanodroplet. With increasing the ratio of solvophilic to block length to solvophobic block length(RH/T), solvophobic sphere, ordered hexagonal phase, onion phase, perforated onion phase and flocculent phase are formed, respectively. Since onion phase has potential application in controlled drug release, it has received wide attention experimentally and theoretically. Our simulation indicates onion phase forms at a certain RH/T(close to but less than 1). A star-block copolymer molecule has two conformations in onion phase: either fully located in a shell or shared by two neighboring shells. Central structure affects onion’s final shape. The molecular number of the copolymer in each shell is a quadratic function of the shell’s radius. The arm number of star-block copolymer has little influence on onion’s structure, but slightly affects the solvent content. Additionally, we studied the influence of arm length on onion’s structure.

Fabrication of conducting polyaniline microspheres using droplet microfluidics

Polyaniline (PANI) is a conducting polymer with very diverse applications in the areas of sensing, bioelectronics, biofuels, toxic metal recovery and rechargeable batteries. In this work, monodispersed PANI microspheres in the semi-conducting range are facilely synthesized via chemical oxidation by using droplet microfluidics. These PANI microspheres are characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), UV-visible spectroscopy and conductivity measurements with three different molar concentrations of the polymer. The effect of the molar ratio of ammonium persulfate to aniline on the morphology, chemical structure and conductivity of the PANI microspheres is investigated. The conductivity of the PANI microspheres is on the order of 10−3 S cm−1 by using our microfluidic platform, comparable to that of the existing PANI nanostructures. In comparison with the existing self-assembly or template methods for PANI synthesis, our droplet microfluidics based procedure provides an inexpensive, rapid, and higher throughput one-step synthesis route for the fabrication of PANI microspheres with controlled size, functionality and biomolecule encapsulation capacity for biosensing and controlled drug release applications.

Temperature-responsive drug delivery systems based on polyaspartamides with isopropylamine pendant groups

To develop poly(amino acid)s with temperature-sensitivity, a series of polyaspartamides with isopropylamide and hydroxyalkylamide pendant groups were synthesized by a successive aminolysis reaction of polysuccinimide. The structure of the resulting polymers was examined by 1H NMR and FT-IR. The polyaspartamide derivatives self-assembled into nanoparticles in water and showed sharp temperature-responsive phase transition behaviour. The phase transition temperature (Tp) could be modulated by the hydrophilic–hydrophobic balance of the copolymer controlled by altering the composition of both pendants. Besides, an antitumor agent, doxorubicin, was successfully loaded into the polymeric nanoparticles via a dialyzing method. The drug release profile was temperature-dependent accelerating significantly above the Tp and decelerating below the Tp. This easily prepared polymeric nanoparticle with excellent biocompatibility and tunable temperature responsiveness has significant potential for controlled drug release applications.

Electrical signals guided entrapment and controlled release of antibiotics on titanium surface

Electrical signals are used to trigger the entrapment and release of antibiotics on the surface of titanium plate. The entrapment of antibiotics relies on the electrochemically induced pH gradient generated at the titanium surface that allows the gelation of an aminopolysaccharide chitosan and codeposition of vancomycin, a common antibiotic, within chitosan gel. The release of vancomycin is controlled by an anodic signal imposed to the titanium plate that causes a pH decrease and erosion of chitosan gel. We show that the on demand entrapment and release of vancomycin at the surface of titanium plate is fundamentally altered and controlled by voltage. We expect that this rapid, mild and facile electrochemical process for antibiotics loading and release will find applications in controlled drug release from titanium implants.

Fabrication of polymeric micelles with core–shell–corona structure for applications in controlled drug release

Thermo-responsive polymeric micelles of poly (ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-lactide)-b-poly(N-isopropylacrylamide) (PEG-P(HEMA-PLA)-PNIPAM) with core–shell–corona structure were fabricated for applications in controlled drug release. The graft copolymer of PEG-P(HEMA-PLA)-PNIPAM was self-assembled into core–shell micelles with a densely PLA core and mixed PEG/PNIPAM shells at 25 °C in aqueous media. By increasing the temperature above the lower critical solution temperature of PNIPAM, these core–shell micelles could be converted into core–shell–corona micelles because of the collapse of PNIPAM block on the PLA core as the inner shell and the soluble PEG block stretching outside as the outer corona. Anticancer drug doxorubicin (DOX) was loaded in the polymeric micelles as a model drug. Compared with polymeric micelles formed by liner PEG-b-PLA-b-PNIPAM triblock copolymer, these polymeric micelles exhibited higher loading capacity, and release of DOX from the polymeric micelles with core–shell–corona structure was well-controlled.

Chlorotrimethyl Silane Coupled Chitosan/Polyacrylamide/Nano Hydroxyapatite Composites for Controlled Drug Release Applications

Chlorotrimethyl Silane Coupled Chitosan/Polyacrylamide/Nano Hydroxyapatite Composites for Controlled Drug Release Applications

Photo and pH dual-responsive polydiacetylene smart nanocontainer

Herein, a novel smart nanocontainer was developed by incorporating photo-responsive azobenzene derivative/cyclodextrin (Azo–CD) supramolecular complex into pH-responsive polydiacetylene (PDA) vesicles matrix. The designed nanocontainer exhibited excellent cell-toxicity, and the controlled release property response to external photo and pH stimuli. The photo-controlled inclusion and exclusion reaction between α-cyclodextrin (α-CD) and azobenzene moiety were used to act as the driving force to induce photo-triggered controlled release behavior of the designed nanocontainer. Moreover, the pH-responsive PDA vesicle matrix endowed the designed system with a controlled release property upon pH variation. The facile preparation procedures and their efficiency of response to the external stimuli render the novel smart nanocontainer potential candidate for future applications in remote controlled drug release.

Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

A solvothermal method has been successfully used to prepare nanostructured hydroxyapatite (HA) hollow spheres with average diameters of about 500 nm and shell thicknesses of about 100 nm in a glycerin/water mixed solvent. Transmission electron microscopy (TEM) and field-emission scanning electron microscopy (FESEM) images show that the shells of the HA hollow spheres are actually composed of nanosheets with thicknesses of about 10 nm. By tuning the glycerin/water volume ratio, two other kinds of HA solid spheres with average diameters of about 6 or 20 μm were assembled from nanoflakes. The properties of the different kinds of spheres as drug delivery carriers were evaluated. Ibuprofen (IBU) was chosen as the model drug to load into the HA samples. The nanostructured HA samples showed a slow and sustained release of IBU. The HA hollow spheres exhibited a higher drug loading capacity and more favorable release properties than the HA solid spheres and thus are very promising for controlled drug release applications.

Study of pH/temperature dual stimuli‐responsive nanogels with interpenetrating polymer network structure

AbstractNanogels with interpenetrating polymer network (IPN) structure based on poly(N‐isopropylacrylamide) (PNIPAM) and poly(acrylic acid) (PAA) were synthesized by in situ polymerization of acrylic acid and N, N′‐methylenebisacrylamide within the PNIPAM nanogels. Their IPN structure was confirmed using transmission electron microscopy after staining by uranyl acetate. The temperature‐ or pH‐dependent hydrodynamic diameters measured using dynamic laser light scattering show that the IPN nanogels have pH and temperature dual stimuli‐responsive properties. As compared to previously reported pH/temperature dual stimuli‐responsive nanogels, these IPN nanogels have the advantage of less mutual interference between the temperature‐responsive and pH‐responsive components, which is beneficial for their applications in controlled drug release and sensors. The temperature‐ and pH‐triggered volume phase transition mechanisms of the IPN nanogels were tested by probing the microenvironment change of their PNIPAM and PAA chains upon phase transition using infrared (IR) absorption spectra measured at different pH values and IR difference spectra obtained by subtracting the IR spectrum obtained before temperature‐induced phase transition from that obtained after phase transition. Copyright © 2012 Society of Chemical Industry

A novel process for coating of silica aerogel microspheres for controlled drug release applications

Aerogels are nanoporous materials with an open-pore structure and high specific surface area. Because of their outstanding properties they have been investigated in immense fields of applications like novel insulation materials, catalysts and catalysts carrier, optics, waste treatment and drug delivery systems. However, the limitation of aerogels (specially hydrophilic ones) in a number of applications is their open-pore structure, allowing the penetration of liquids therein resulting in destruction of their textural properties. Applying a polymeric coating layer on aerogels surface can be a solution for this problem and can open a wide window of new applications for aerogels, especially in pharmaceutical industry. This work suggests a novel process for coating of aerogels with polymeric materials using spouted bed technology. Firstly, spherical silica aerogel particles with a high surface area up to 1100m2/g and particles diameter ranging from 200μm to few millimetres were produced. Then, the aerogel particles were loaded with a model drug (Ibuprofen) by adsorption from supercritical CO2 phase. The loaded aerogel particles were coated with different polymeric materials in a slit-shaped spouted fluidized bed with two horizontal gas inlets and adjustable gas supply. The corresponding polymers were sprayed as an aqueous suspension or as melts. The process conditions for coating (coating material, fluidization air flow rate, temperature, etc.) were optimized accordingly. The physical, mechanical, structural and release properties of the resulting formulations were evaluated. This technology allows to provide a specific release mechanism of pharmaceuticals (thermal, pH-sensitive or enzyme triggered release) from aerogels and to broaden aerogel applications in pharmaceutical technology.

Microfluidic synthesis of advanced microparticles for encapsulation and controlled release

We describe droplet microfluidic strategies used to fabricate advanced microparticles that are useful structures for the encapsulation and release of actives; these strategies can be further developed to produce microparticles for advanced drug delivery applications. Microfluidics enables exquisite control in the fabrication of polymer vesicles and thermosensitive microgels from single and higher-order multiple emulsion templates. The strategies used to create the diversity of microparticle structures described in this review, coupled with the scalability of microfluidics, will enable fabrication of large quantities of novel microparticle structures that have potential uses in controlled drug release applications.

Fluorine-containing pH-responsive core/shell microgel particles: preparation, characterization, and their applications in controlled drug release

A kind of novel fluorine-containing pH-responsive core/shell microgels poly(DMAEMA-co-HFMA)-g-PEG were prepared via surfactant-free emulsion polymerization using water as the solvent. The well-defined chemical structure of the copolymers was characterized by FTIR, 1H-NMR, 19F-NMR, and elemental analysis. The microgel particles were studied by florescence probe technique, dynamic light scattering, and zeta potential measurement; the microgels displayed a significant pH-responsive behavior. Furthermore, the cytotoxicity assay indicated that the copolymer microgels had low toxicity, and 5-FU-loaded microgels offered a certain killing potency against cancer cells. In addition, the drug loading and in vitro drug release demonstrated that 5-FU was successfully incorporated into polymeric microgels, and the drug-loaded microgels showed a marked pH-dependent drug release behavior. This study suggests that the poly(DMAEMA-co-HFMA)-g-PEG microgels play an important role in the release mechanism stimulated by the change in the pH and have potential applications as a controlled drug release carrier.

Keratin films from chicken feathers for controlled drug release

Abstract summaryDuring the past two decades significant advances have been made in the development of biomaterials for biomedical applications, especially biomaterials based on natural polymers. In this paper, we report the preparation of protein films for controlled drug release applications. This

Self-assembled nanoparticles from thermo-sensitive polyion complex micelles for controlled drug release

Self-assembled nanoparticles from thermo-sensitive polyion complex (PIC) micelles comprised of poly( t-butyl acrylate- co-acrylic acid)- b-poly( N-isopropylacrylamide) [P( tBA- co-AA)- b-PNIPAM] core–shell micelles and graft copolymer chitosan- g-poly( N-isopropylacrylamide) (CS- g-PNIPAM) were developed for applications in controlled drug release. The PIC micelles nanoparticles had a multi-layer core–shell–corona structure with hydrophobic P tBA as the inner core, negatively charged PAA and positively charged CS forming the middle layer as the shell, and thermo-sensitive PNIPAM as the outer corona. The molar ratio of P( tBA- co-AA)- b-PNIPAM to CS- g-PNIPAM affected the functionalities and hydrodynamic diameters of nanoparticles. Release of doxorubicin (DOX) from micelles was suppressed at neutral solutions due to the stability of electrostatic interactions but accelerated at acidic solutions or high temperatures above LCST. This study presents new micelles with a functional inner shell whose structure can be rapidly damaged to release charged drugs when the microenvironment of micelles changed.

Fluorine-containing thermo-sensitive core/shell microgel particles: Preparation, characterization, and their applications in controlled drug release

A novel series of fluorine-containing thermo-sensitive core/shell microgel particels, poly[N-isopropylacrylamide-co-2,2,3,4,4,4-Hexafluorobutyl methacrylate-co-Poly(ethylene glycol) methyl ether methacrylate] [P(NIPAAm-co-HFMA-co-MPEGMA)], were prepared via surfactant free emulsion polymerization. The composition of the copolymer microgels was characterized by FTIR, 1H NMR, and 19F NMR. Subsequently, the thermo-responsive behavior of the microgels was studied by UV–vis spectroscopy, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. The copolymer microgels exhibited a lower critical solution temperature (LCST) above the normal human physiological temperature. When the temperature was above the LCST, the hydrophobicity of the microgels increased significantly, and the average hydrodynamic diameter decreased greatly. TEM results showed that the copolymer microgels formed loose core–shell spherical particles below the LCST, but above the LCST, the particles became compact and the core–shell structure was not obvious. The drug loading and in vitro release were studied with 5-fluorouracil as a model drug. The result showed that the rate and amount of the drug release became much higher above the LCST. In a word, the study indicated that the fluorine-containing thermo-sensitive copolymer microgels had promising potential applications as a “smart” drug carrier in biomedical field.

Bimodal Mesoporous Silicas Functionalized with Different Level and Species of the Amino Groups for Adsorption and Controlled Release of Aspirin

The synthesis of modified bimodal mesoporous materials (BMMs) with a small pore size of around 2.9 nm and a large pore size of about 20 nm has been performed via post-grafting methods. To study the application of functionalized BMMs in drug delivery, loading and releasing profiles using aspirin as model drug were carried out. XRD, SEM, TEM, N2 adsorption, FT-IR, 29Si-NMR, TG and UV-Vis spectroscopy were used to characterize the related samples. The post-grafting modification was performed through the weak chemical interaction or hydrogen bonding in between OH groups of the mesopore surface and 3-aminopropyltriethoxysilane (N-TES) or 3-(2-aminoethylamino) propyItrimethoxysilane (NN-TES). The results showed that N-TES groups with different amount and NN-TES groups were successfully incorporated onto the mesopore surface. Subsequently, the controlled aspirin delivery properties from the resulting modified BMMs were investigated in detail. The aspirin adsorption experiments indicated that the adsorption capacities of modified BMMs were improved with the increasing amount of N-TES groups, while the NN-TES functionalized samples showed higher adsorption capacity than N-TES modified samples with the same ratio of modification. The most reason is that the interaction between the NN-TES groups and aspirin molecules is stronger than that between the N-TES groups and aspirin molecules. The in vitro tests exhibited that aspirin release behaviors mainly depended on the variation of the amount and species of the functional groups in mesoporous carries. According to the Korsmeyer-Peppas model, it is found that the kinetic release constant k reduced with the increase amount of the amino groups on the mesopore surface of modified BMMs, suggesting that the aspirin release rate from the pores of BMMs was influenced directly by organic groups on the surface. The release exponent n of all the situations were above 0.5, indicating the drug release mechanism followed a non-Fickian model that was diffusion based. Therefore, this type of materials described in this paper is of strong potential for the controlled drug release applications.