Drug Carrier Material Research Articles

Crosslinked casein-based micelles as a dually responsive drug delivery system

Crosslinked casein micelles with a dual pH and protease drug triggered release can be applied as a promising hydrophobic drug carrier material.

Chitosan capped nanoscale Fe-MIL-88B-NH2 metal-organic framework as drug carrier material for the pH responsive delivery of doxorubicin

In recent years nanoscale metal-organic frameworks (NMOFs) are contributing as an effective material for use in drug delivery and imaging applications due to their porous surfaces and easy surface modifications. In this work, Fe-MIL-88B-NH2 NMOFs were successfully synthesized on facile hydrothermal route and 2-aminoterephthalic acid (NH2-BDC) was employed as a bridging ligand to activate amine functional groups on the surface. Amine functional groups not only serve as a structure stabilizing agent but also enhance the loading efficiency of the doxorubicin (DOX) anticancer drug. A pH responsive DOX release was realized by introducing a positively charged chitosan (Chi) capping layer. Upon Chi-coating, cleavage was observed in the Fe-MIL-88B-NH2 structure at acidic pH, while gel-like insoluble structure was formed at basic pH. By utilizing this phenomenon, a pH responsive DOX release system was developed by using Chi capped Fe-MIL-88B-NH2 NMOFs under the designed pH (4.0–8.0). The results suggest the Chi capped Fe-MIL-88B-NH2 can be a promising candidate for future pH responsive drug delivery systems.

Preparation and the controlled release effect study of graphene oxide-modified poly(ε-caprolactone)

ABSTRACTFunctionalized graphene oxide-modified poly(ε-caprolactone) composites ((graphene oxide)GO/PCL) were successfully synthesized by Steglich esterification for drug applications of controlled release. Lomefloxacin (LMF) was selected as a model drug to investigate its controlled release properties. The controlled release effect of the LMF-contained pills of the GO/PCL and polylactic acid blend was evaluated. In contrast to the pure PCL, GO/PCL could effectively adjust the time of drug release and release the drug at a constant rate, achieving the controlled release requirements. Furthermore, different additive amounts of graphene oxide have different effects on adjusting the time of controlled release, while the best result obtained under the ratio is 4% GO/PCL as carrier of drug. Thus, high-quality drug carrier materials are obtained which are more suitable for clinical use. Exploring the optimum addition of graphene oxide is very significant for the development of GO/PCL carrier material.

Unprecedented α-cyclodextrin metal-organic frameworks with chirality: Structure and drug adsorptions

An assembly of cyclodextrin metal-organic frameworks (CD-MOFs) has aroused extensive research interests due to their excellent encapsulation capacity and biocompatibility. In this work, starting from the chiral building block α-cyclodextrin (α-CD), a novel α-CD-MOF compound with left-handed chiral helices, [Na(H2O)(C36H60O30)]·H2O (Na-α-CD-MOF), was synthesized through changing the diffusion solvent, and then structurally characterized. Single crystal X-ray diffraction analysis reveals that Na-α-CD-MOF exhibits a 3D left-handed helical chiral framework with large cavities (740Å3). The result of a drug adsorption assay shows Na-α-CD-MOF possesses a more efficient drug adsorption capacity than α-CD matrix, and the solubility of the drug adsorbed in Na-α-CD-MOF can be greatly enhanced. All the results, including the lower cytotoxicity, indicate that Na-α-CD-MOF is an excellent kind of renewable, environmental friendly and biocompatibility drug carrier material.

Fabrication of dual-sensitive keratin-based polymer hydrogels and their controllable release behaviors

Using feather keratin (FK) as a biocompatible and inexpensive biopolymer, a kind of dual-sensitive keratin-based polymer hydrogel (FK/PNiPA/PIAc-Gel) with interpenetrating network structure was prepared by two-step polymerization of N-isopropyl acrylamide (NiPA) and itaconic acid (IAc) in presence of crosslinker. After being characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy, its swelling behaviors and environmental sensitivity were investigated. The obtained biopolymer based hydrogel has good swelling and deswelling performance, and it is sensitive to pH value, temperature and salts of environment. Using anticancer drug, doxorubicin hydrochloride (Dox·HCl), and Bovine serum albumin (BSA) as different drug molecules, its release behaviors in different environment were investigated. It was found that the release behaviors of FK/PNiPA/PIAc-Gel were controllable via adjusting pH value or temperature of environment. The cumulative release of the anticancer drug (Dox·HCl) reached 93.3% within 16 h, and the cumulative release rate of macromolecular drug (BSA) got to 75.9% in 24 h. In summary, the keratin-based biopolymer hydrogel with interpenetrating network structure, pH-sensitivity and temperature sensitivity are potentially applied to sustain drug carrier and humid medicinal material in the biomedical field or clinical nursing field.

Synthesis and characterization of imidacloprid microspheres for controlled drug release study

Polypropylene carbonate (PPC) was synthesized by the alternating copolymerization of carbon dioxide with propylene oxide (PO). Imidacloprid microspheres were prepared by emulsion solvent evaporation, PPC as the drug-carrier material. The effect of the reaction conditions on drug loading (DL) and entrapment efficiency (EE) was examined. High DL of 45.03% was achieved at the methylene chloride and water volume ratio of 1:1, polyvinyl alcohol (PVA)-1788 concentration of 1%, imidacloprid and PPC mass ratio of 1:3, and shear rate of 10,000r/min. When imidacloprid and PPC mass ratio was 2:3, high EE of 77.91% was obtained. Through the scanning electronic microscopy (SEM) the hollow structure of the microspheres was studied. The effects of shear rate on the diameter and morphology of microspheres were studied by the SEM. The perfect microspheres were obtained at the 10,000r/min shear rate. The release behavior of imidacloprid encapsulated in the microspheres was studied. The experimental results indicated that the microspheres had a property of sustained drug release.

Fabrication of graphene oxide-modified chitosan for controlled release of dexamethasone phosphate

Functionalized graphene oxide with its unique physical and chemical properties is widely applied in biomaterials, especially in drug carrier materials. In the past few years, a number of different drugs have been loaded on functionalized graphene oxide via π–π stacking and hydrophobic interactions. The present report described a new approach, dexamethasone phosphate successfully loaded onto graphene oxide–chitosan nanocomposites as drug carrier materials by covalent bonding of phosphate ester linkage. Compared with the graphene oxide–chitosan nanocomposites that dexamethasone phosphate was loaded on via simple physical attachment, covalently linked composites as drug carrier materials were more biocompatible which effectively reduced the burst release of drug, and controlled the release of drug in different pH conditions.

Characterization of Electrospun Nanofibrous Scaffolds for Nanobiomedical Applications

The electrospinning method is employed in the production of porous fiber scaffolds, and the usage of electrospun scaffolds especially as drug carrier and bone reconstructive material such as implants is promising for future applications in tissue engineering. The number of publications has grown very rapidly in this field through the fabrication of complex scaffolds, novel approaches in nanotechnology, and improvements of imaging methods. Hence, characterization of these materials has also grown significantly important for getting satisfied and accurate results. This advantageous and versatile method is ideal for mimicking bone extracellular matrix, and many biodegradable and biocompatible polymers are preferred in the field of bone reconstruction. In this study, gelatin, gelatin/nanohydroxyapatite (nHAp) and gelatin/PLLA/nHAp scaffolds were fabricated by the electrospinning process. These composite fibers showed clear and continuous morphology according to observation through a scanning electron microscope and their component analyses were also determined by Fourier transform infrared spectrometer analyses. These characterization experiments revealed the great effects of the electrospinning method for biomedical applications and have an especially important role in bone reconstruction and production of implant coating material.

Functional poly(p-phenylene)s as targeting and drug carrier materials

ABSTRACTPolymers have a substantial attention in drug delivery systems owing to the diverse intrinsic advantages. It is important to carry the drug to the target site and release to exert its effects. Herein, poly(p-phenylene)s with amino and poly(ethylene glycol) substituents (PPP-NH2-g-PEG) were used as a carrier for doxorubicin (DOX), an anticancer drug, and haloperidol, a sigma receptor targeting ligand. Both human cervix adenocarcinoma cell line (HeLa) and human keratinocyte cell line (HaCaT) having different Sigma receptor 1 (SigmaR1) expression levels were compared. HeLa was found to express twofold SigmaR1 compared to HaCaT cells. Cell imaging studies showed that, DOX cell uptake was higher in HeLa cells when targeted with haloperidol.

Degradation behavior and biosafety studies of the mPEG-PLGA-PLL copolymer.

In a previous study, a novel biodegradable multiblock copolymer, monomethoxy(poly-ethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine) (PEAL), was developed as a new drug carrier material. It is imperative to study the biocompatibility and degradation behavior of PEAL to pave the way for clinical applications. Here, we systematically demonstrated that the PEAL copolymer has the appropriate hydrophilicity and biosafety. The degradation rate of the PEAL films was obtained by observing changes in mass, molecular weight (Mw), Mw distribution and degradation products. The degradation rate was observed to have a highly positive correlation with the pH of the medium and negative correlation with the ratio of lactic acid to glycolic acid (LA/GA). Cytotoxicity tests indicated that the degradation products of the copolymer were non-toxic to cells. In zebrafish embryos, the PEAL nanoparticles had no obvious impact on heart rate, production of reactive oxygen species, mortality, or cell apoptosis, and they were observed to have a long circulation time. Therefore, the PEAL copolymer has great potential for use as a drug carrier material.

Development of an itraconazole encapsulated polymeric nanoparticle platform for effective antifungal therapy.

This study is to develop a novel itraconazole-loaded nanoparticle (ITZ-NP) platform for effective antifungal therapy. First, the monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-b-PLA) copolymer was prepared as a drug carrier material. Then the nanoparticles were formulated via a simple film hydration method. The copolymer and nanoparticles were characterized by standard methods, including 1H NMR, 13C NMR, FT-NIR, DSC, XRPD, and particle size, zeta potential, morphology and physical examination. Furthermore, in vitro itraconazole release and antifungal activity were intensively evaluated. The results showed that the formed nanoparticles significantly enhanced sustained drug release and inhibited fungal infection. In addition, ITZ-NPs caused very mild hemolysis and slight venous irritation, indicating much better biocompatibility than marketed cyclodextrin formulations of ITZ. An Iin vivo biodistribution study via intravenous injection showed that ITZ-NPs could be effectively retained in blood circulation and selectively distributed in RES-rich organs compared with commercial cyclodextrin injection, with the verification of Re, Te, RTe and Ce. In summary, the developed ITZ-NPs could reduce systemic toxicity, improve antifungal activity and act as a potential intravenous formulation of ITZ.

Preparation and release behaviour of mPEG-PLA α-asarone nanoparticles designed for nasal administration

Taking α-asarone as model drug, mono methoxy polyethylene glycol-polylactic acid copolymer (mPEG-PLA) as the drug carrier material to prepare drug-loading nanoparticles by premix membrane emulsification for nasal administration. The prepared nanoparticles were spherical with smooth surface and average particle size of 360 nm. Polydispersity index (PDI) was 0. 030, average drug loading of (11.5 ± 0.045) % (n = 3), and the encapsulation efficiency of (86.34 ± 0.11) % (n = 3). X-ray diffraction and differential scanning calorimetry results showed that, α-asarone existed in mPEG-PLA carrier in amorphous or molecular state, different from simple physical mixture. In the in vitro release test in simulated human nasal cavity, α-asarone apis can be released quickly at close to 94% at 102 h, in line with the first-order kinetics (R² = 0.981 9). mPEG-PLA drug-loading nanoparticles release only 54%, with slow release effect, in line with Riger-Peppas model (R² = 0.967 9, n = 0.630 2), for non-fick diffusion, released by the spread of drugs and skeleton dissolution dual control. This provided the foundation for nasal drug delivery in vivo pharmacokinetic study.

Synthesis of amphiphilic alginate derivatives and electrospinning blend nanofibers: a novel hydrophobic drug carrier

As a kind of novel hydrophobic drug carrier materials, the drug-loaded nanofibers were successfully fabricated using amphiphilic alginate derivative (AAD) and poly (vinyl alcohol) (PVA) by electrospinning method. The AAD was synthesized by amide linkage attachment of octylamine onto the carboxylic group of alginate, which was characterized by the means of elemental analysis, FT-IR spectrometer, 1H NMR spectrometer and fluorescence measurement. Experimental results showed the amidation of alginate was successful, in which the degree of modification was 0.27 and the critical aggregation concentration in 0.15 mol/L aqueous NaCl solution was 0.43 mg/mL. The octyl groups of AAD could effectively make alginate chains flexible and enhance chain entanglements through the hydrophobic interactions between octyl groups. In contrast to sodium alginate (SA)/PVA blend solutions, AAD/PVA blend solutions showed more excellent electrospinnability. Additionally, the different volume ratios of SA or AAD to PVA played an important role in the formation and morphology of the electrospun blend nanofibers. Although the amidation of alginate could not fundamentally alter the spinnability of alginate, the content of alginate in the blend nanofibers was appropriately increased. The new generated drug-loaded AAD/PVA (20/80) blend nanofibers exhibited relatively continuous and uniform nanofibers with the average diameter of 191.72 nm. Compared to the drug-loaded SA/PVA (20/80) blend nanofibers, the drug-loaded AAD/PVA (20/80) blend nanofibers presented a sustained release performance with the slow release of about 76 % λ-cyhalothrin during the initial period of 10 h.

Modified biofunctional p(tannic acid) microgels and their antimicrobial activity

Crosslinked poly(tannic acid) micro particles, p(TA), were synthesized using trimethylolpropane triglycidyl ether (TMPGDE) as crosslinker in a single step with high yield (73±6%). The obtained p(TA) microgels possessed negative zeta potential, −27mV, and the surface charge can be tuned by chemical modification using various modifying agents, such as 3-chloro-2-hydroxypropyl ammonium chloride (CHPACl) and chloro sulfonic acid (CSA) to generate microgels with different zeta potentials, e.g., −18mV and −36mV, respectively. Modified p(TA) microgels are found to be thermally less stable than bare p(TA) particles. Additionally, upon chemical modification of p(TA) particles, the antioxidant capacity of the p(TA) microgels decreased confirming the utilization of some of the phenolic groups, the main functional groups responsible for the antioxidant property of TA moieties. Moreover, the antimicrobial properties increased approximately four fold against three common bacterial strains; Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, and Bacillus subtilis ATCC 6633. P(TA) microgels as TA molecules have a natural capability to reduce metal ions, allowing in situ reduction of absorbed Ag and Cu ions to the corresponding metal nanoparticles within the p(TA) microgel network. The composite p(TA)-M (M: Ag or Cu) nanoparticle demonstrated superior antimicrobial activity against the mentioned bacteria compared to the bare p(TA) microgels. Moreover, bare and modified p(TA) microgels are shown to be drug carrier materials by loading three model drugs, phenylephrine HCl (PHE), trimethoprim (TMP), and naproxen (NP), and releasing them in phosphate buffer saline PBS (pH 7.4) at 37.5°C.

Research on redox-responsive mesoporous silica nanoparticles functionalized with PEG via a disulfide bond linker as drug carrier materials

In this paper, mesoporous silica nanoparticles (MSNs) functionalized with polyethylene glycol (PEG, Mw = 1000 and 5000 Da) via a disulfide bond linker (named as MSNs-SS-PEG1000 and MSNs-SS-PEG5000, respectively) as the novel drug delivery carrier was successfully synthesized. The particle size, surface structural properties, and pore size of these materials were investigated by dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), nitrogen adsorption–desorption measurements, and X-ray diffraction (XRD). Both MSNs-SS-PEG1000 and MSNs-SS-PEG5000 exhibited the spherical particles with an average diameter of about 200 nm, typical micropore structures, and intact pore interconnection. Moreover, the releases of doxorubicin hydrochloride (DOX) from these materials in different concentrations of glutathione (GSH) were investigated. The release of DOX from MSNs-SS-PEG1000 and MSNs-SS-PEG5000 revealed the redox-responsive characteristic and the drug release content increased with the increase of GSH concentration. Therefore, MSNs-SS-PEG might be a promising carrier material in delivering anticancer drugs.

The Drug Loading Kinetics Mechanism of Ion Exchange Fiber as a Novel Kind of Drug Carrier Material

The adsorption of Fenazoxine hydrochloride was investigated by performing batch kinetic sorption experiments. Experiments were carried out as function of contact time, initial concentration. Adsorption data were modeled using the pseudo-first-order and pseudo-second-order kinetics equations. It showed that the pseudo-second order kinetic equation can describe the adsorption kinetics best. The results indicate that ion-exchange fiber is suitable as drug carriers for loading drugs.

Preparation and Drug-Release Kinetics of Porous Poly(L-lactic acid)/Rifampicin Blend Particles

Porous polymer spheres are promising materials as carriers for controlled drug release. As a new drug-carrier material, blend particles composed of poly(L-lactic acid) (PLLA) and rifampicin were developed using the freeze-drying technique. The blend particles exhibit high porosity with a specific surface area of 10–40 m2 g−1. Both the size and porosity of the particles depend on the concentration of the original solution and on the method of freezing. With respect to the latter, we used the drop method (pouring the original solution dropwise into liquid nitrogen) and the spray method (freezing a mist of the original solution). The release kinetics of rifampicin from the blend particles into water depends significantly on the morphology of the blend particles. The results show that the release rate can be controlled to a great extent by tuning the size and porosity of the blend particles, both of which are varied by parameters such as the solution concentration and the method of freezing.

Modification of chitosan by using samarium for potential use in drug delivery system

In the presence of hydroxyl and amine groups, chitosan is highly reactive; therefore, it could be used as a carrier in drug delivery. For this study, chitosan–Sm complexes with different concentrations of samarium from 2.5 to 25wt.% have been successfully synthesized by the impregnation method. Chitosan combined with Sm3+ ions produced a drug carrier material with fluorescence properties; thus, it could also be used as an indicator of drug release with ibuprofen (IBU) as a model drug. We evaluated the spectroscopic and interaction properties of chitosan and Sm3+ ions, the interaction of chitosan–Sm matrices with IBU as a model drug, and the effect of Sm3+ ions addition on the chitosan ability to adsorb the drug. The result showed that the hypersensitive fluorescence intensity of chitosan–Sm (2.5wt.%) is higher than the others, even though the adsorption efficiency of chitosan–Sm 2.5wt.% is lower (29.75%) than that of chitosan–Sm 25wt.% (33.04%). Chitosan–Sm 25wt.% showed the highest efficiency of adsorption of ibuprofen (33.04%). In the release process of ibuprofen from the chitosan–Sm–IBU matrix, the intensity of orange fluorescent properties in the hypersensitive peak of 4G5/2→6H7/2 transition at 590nm was observed. Fluorescent intensity increased with the cumulative amount of IBU released; therefore, the release of IBU from the Sm-modified chitosan complex can be monitored by the changes in fluorescent intensity.

The Synthesis of the Amphiphilic Triblock Cationic Copolymer mPEG-PCL-PDMAEMA the Synthesis and its Impact Study on the Load and Transfected of siRNA

Polyphosphate is a biocompatible, modified and functionalized biodegradable polymer. It has a broad application prospects in the field of medical biomaterials. It is an excellent drug carrier material. In this essay, through the open-loop and ATRP polymerization, it synthesizes biodegradable amphiphilic triblock copolymer PEG-PCL-PDMAEMA. Composition and structure of the polymer is Characterized by 1H NMR and IR In this essay. This essay also studies that the polymer in water can be self-assembled to form a stable nanoparticles; The polymer micelle can form composite particles with siRNA,. This essay also studies the load and transfection of the polymer micelles on siRNA.

Wet microcontact printing (µCP) for micro-reservoir drug delivery systems

When micro-reservoir-type drug delivery systems are fabricated, loading solid drugs in drug reservoirs at microscale is often a non-trivial task. This paper presents a simple and effective solution to load a small amount of drug solution at microscale using ‘wet’ microcontact printing (µCP). In this wet µCP, a liquid solution containing drug molecules (methylene blue and tetracycline HCl) dissolved in a carrier solvent was transferred to a target surface (drug reservoir) by contact printing process. In particular, we have investigated the dependence of the quantity and morphology of transferred drug molecules on the stamp size, concentration, printing times, solvent types and surfactant concentration. It was also found that the repetition of printing using a non-volatile solvent such as polyethylene glycol (PEG) as a drug carrier material actually increased the transferred amount of drug molecules in proportion to the printing times based on asymmetric liquid bridge formation. Utilizing this wet µCP, drug delivery devices containing different quantity of drugs in micro-reservoirs were fabricated and their performance as controlled drug delivery devices was demonstrated.