Release Of Aspirin Research Articles

Simultaneous Application of Photothermal Therapy and an Anti‐inflammatory Prodrug using Pyrene–Aspirin‐Loaded Gold Nanorod Graphitic Nanocapsules

AbstractPhotothermal therapy (PTT) has been extensively developed as an effective approach against cancer. However, PTT can trigger inflammatory responses, in turn simulating tumor regeneration and hindering subsequent therapy. A therapeutic strategy was developed to deliver enhanced PTT and simultaneously inhibit PTT‐induced inflammatory response. 1‐Pyrene methanol was utilize to synthesize the anti‐inflammatory prodrug pyrene–aspirin (P‐aspirin) with a cleavable ester bond and also facilitate loading the prodrug on gold nanorod (AuNR)‐encapsulated graphitic nanocapsule (AuNR@G), a photothermal agent, through π–π interactions. Such AuNR@G‐P‐aspirin complexes were used for near‐infrared laser‐triggered photothermal ablation of solid tumor and simultaneous inhibition of PTT‐induced inflammation through the release of aspirin in tumor milieu. This strategy showed excellent effects in vitro and in vivo.

Simultaneous Application of Photothermal Therapy and an Anti-inflammatory Prodrug using Pyrene-Aspirin-Loaded Gold Nanorod Graphitic Nanocapsules.

Photothermal therapy (PTT) has been extensively developed as an effective approach against cancer. However, PTT can trigger inflammatory responses, in turn simulating tumor regeneration and hindering subsequent therapy. A therapeutic strategy was developed to deliver enhanced PTT and simultaneously inhibit PTT-induced inflammatory response. 1-Pyrene methanol was utilize to synthesize the anti-inflammatory prodrug pyrene-aspirin (P-aspirin) with a cleavable ester bond and also facilitate loading the prodrug on gold nanorod (AuNR)-encapsulated graphitic nanocapsule (AuNR@G), a photothermal agent, through π-π interactions. Such AuNR@G-P-aspirin complexes were used for near-infrared laser-triggered photothermal ablation of solid tumor and simultaneous inhibition of PTT-induced inflammation through the release of aspirin in tumor milieu. This strategy showed excellent effects in vitro and in vivo.

Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles.

IntroductionMembranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM).MethodsIn this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration.ResultsDrug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group.ConclusionThis study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration.

Injectable thermosensitive alginate/β-tricalcium phosphate/aspirin hydrogels for bone augmentation.

In this study, an injectable and thermo-sensitive alginate/β-tricalcium phosphate hydrogel (TSAH/β-TCP) was prepared for aspirin release to a bone defect. Aspirin was dissolved into a mixture of poly(N-isopropylacrylamide) (PNIPAAm), an aminated alginate-g-PNIPAAm co-polymer, and β-TCP powders. Scanning electron microscopy showed that TSAH/β-TCP had an interconnected porous microstructure with a porosity of 86.78%. The cross-linked hydrogel released approximately 40% of the aspirin in the first 3 days and then slowly released the remainder. At a low concentration (≤100 μg/mL), aspirin did not promote cell proliferation, but enhanced the alkaline phosphatase activity, and osteocalcin (OCN) and collagen I expression of human bone marrow-derived mesenchymal stem cells. The TSAH/β-TCP/aspirin hydrogel was injected into the periosteum of the rat cranial bone, and its in vivo bone-forming ability was evaluated at 12 weeks. A bone morphogenetic protein 2 (BMP-2)-loaded TSAH/β-TCP hydrogel was injected as a control. Micro-computed tomography showed that the percentage of mineralized tissue in the TSAH/β-TCP/BMP-2 and TSAH/β-TCP/aspirin groups were similar and significantly higher than that in the TSAH/β-TCP group. Immunohistochemical staining showed considerable expression of OCN, especially in the TSAH/β-TCP/BMP-2 and TSAH/β-TCP/aspirin groups. These results suggest that the injectable TSAH/β-TCP/aspirin hydrogel has great potential for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1739-1751, 2018.

Controlled release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity

This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h−0.61. The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers.

46 Sandwich-type ethylcellulose films for controlled release of anti-restenosis drugs

Objectives Restenosis is a response of the vessel wall to balloon-induced injury and is characterized primarily by elastic recoil of the vessel wall and a series of pathological processes including thrombus, inflammation and vascular smooth muscle cell (VSMC) proliferation. To treat restenosis, appropriate drug delivery vehicles are needed which can release therapeutic agents targeting different symptoms into blood vessels in a controlled manner. The main objective of the present study was to prepare sandwich-type ethyl cellulose films with high performance for efficient drug loading and controlled drug release for restenosis treatment. Methods Sandwich-type ethyl cellulose films loaded with probucol for treating coronary artery disease, or aspirin as an antithrombotic drug, were prepared by casting three individual layers in sequence using an ethyl cellulose/toluene solution. On a glass plate, the first ethyl cellulose layer (bottom layer) was cast without drugs, on to which the middle layer containing probucol or aspirin was then cast. After solvent evaporation at room temperature, a third top layer was cast on to the middle layer. The obtained drug-loading films were further dried at room temperature under vacuum. Results The sandwich-type ethyl cellulose films exhibited a drug loading content (DLC) of 12.1 ± 0.9% and a drug loading efficiency (DLE) of 73.5 ± 3.6% for aspirin, and a DLC of 11.0 ± 0.8% and a DLE of 69.3 ± 3.4% for probucol. Under physiological conditions (37°C, pH 7.4), the release half-life of aspirin from the films was 2.7 ± 0.2 hours, while that of probucol was 7.1 ± 0.6 days. The two drugs showed totally different release behaviors, which can be employed in combination to treat restenosis. Conclusion Sandwich-type ethylcellulose films loaded with probucol or aspirin were successfully prepared and showed ability to release the two drugs in different ways: rapid release of aspirin to treat thrombus and inflammation typical of early-stage restenosis, and sustained release of probucol for inhibition of VSMC proliferation frequently seen in the later stage of restenosis. These drug-loaded ethylcellulose films provide new insight into restenosis therapy.

A novel porous aspirin-loaded (GO/CTS-HA)n nanocomposite films: Synthesis and multifunction for bone tissue engineering

A novel porous graphene oxide (GO)/chitosan (CTS)-hydroxyapatite (HA) nanocomposite film was successfully prepared for the first time by combining layer-by-layer (LBL) assembly technology with biomimetic mineralization method. The LBL technology was used to control the thickness of film as well as induce the biomimetic mineralization of biocompatible HA. The obtained (GO/CTS-HA)n film provided ideal platform for the proliferation of mouse mesenchymal stem cells (mMSCs). The pore size in the film is about 300nm, and the porous architecture made the film have high aspirin loading efficiency. Also the accumulated loading dosage could be adjusted by the film thickness, and the sustained release of aspirin could ensure well anti-inflammatory effect. The above advantages may alleviate the pain of patients and give the better environment for bone regeneration. This multifunctional aspirin-loaded (GO/CTS-HA)n film provided an inspiration for the synthesis of novel porous inorganic/biomacromolecule nanocomposite films as the biocoatings applied in bone tissue engineering.

Sustained release of aspirin and vitamin C from titanium nanotubes: An experimental and stimulation study

Anodization is a promising method to change the topography and wettability of titanium (Ti) implant. The formed TiO2 nanotubes (TiNTs) arrays could enhance the biological properties of Ti implants. In this study, to investigate the possibility of TiNTs arrays on a Ti implant surface as nano-reservoirs for small molecular drugs when using in orthopedic and dental prosthesis, TiNTs on a Ti implant surface were prepared. Then, aspirin and/or vitamin C were loaded into TiNTs as model drugs. Meanwhile, low molecular weight polylactic acid (PLA, Mw=3000) was synthesized and loaded alternately along with aspirin or vitamin C. The release rates of aspirin and vitamin C with/or without PLA loading were investigated by using a UV–Vis spectrometer. The results showed that when loading without PLA, drugs released quickly with presence of burst release. However, when loading with PLA, the cumulative release duration of aspirin and vitamin C was prolonged to over 240h. Molecular dynamics (MD) simulation and dissipative particle dynamics (DPD) simulation results proved that when loading with PLA, PLA molecules aggregated gradually and formed clusters or micelles in these nanotubes. Meanwhile, drug molecules were captured and distributed inside the PLA matrix, which retarding the release of drugs. Only when PLA micelles degrade gradually in body fluid, drugs could be released slowly from nanotubes. These knowledge laid ground basis for the following biological experiments.

Selective detection and controlled release of Aspirin over fluorescent amino-functionalized metal–organic framework in aqueous solution

Aspirin, as a traditional anti-inflammatory drug, also leads to some side-effect due to inapposite dose. Simple and sensitive sensors capable of detecting Aspirin would have a significant relevance for human bodies. In this work, a highly selective and sensitive fluorescence probe for detecting Aspirin has been developed based on luminescent Zr-based metal–organic frameworks (MOFs) with accessible channels and functional sites (free amino group). The MOFs show excellent luminescence and good fluorescence stability in aqueous environment. In the presence of Aspirin, the fluorescence would enhance dramatically (∼20.77 times as much as that of without Aspirin) due to the intermolecular hydrogen-bonding interaction between free-NH2 in MOFs and Aspirin. The proposed detecting system shows a low detection limit (0.02μM) and a broad liner range (0.02–200μM) for Aspirin detection. Most importantly, it also expresses good capacity for controlled release of Aspirin in PBS buffer solution (pH 7.4), which has a higher loading content (46%) than some Aspirin loading system. Considering its simple, cost-effective, environmental-friendly as well as combining detection and controlled release, we expect the system will have great potential for biological analysis.

Structure, molecular simulation, and release of a spirin from intercalated Zn–Al-layered double hydroxides

Aspirin or acetylsalicylic acid (AA), a non-steroidal anti-inflammatory drug, is intercalated into Zn–Al-layered double hydroxides (ZnAl-LDHs) by co-precipitation and reconstruction methods. The composition, structure, and morphology of the intercalated products as well as their release behavior are determined experimentally and theoretically by Material Studio 5.5. Experimental results disclose the strong interaction between the LDHs sheets and AA in the intercalated ZnAl-LDHs produced by co-precipitation and slow release of AA from the intercalated ZnAl-LDHs in both phosphate buffered saline (PBS) and borate buffered saline (BBS) solutions. The percentage of AA released from the ZnAl-LDHs prepared by both methods in PBS (96.87% and 98.12%) are much more than those in BBS (68.59% and 81.22%) implying that both H4BO4− and H2PO4− can exchange with AA in the ZnAl-LDHs. After AA is released to PBS, ZnAl-LDHs break into small pieces. The experimental results are explained theoretically based on the calculation of the bonding energy between the anions and LDHs sheets as well as the AlO bond length change in the LDHs sheets.

IN VITRO RELEASE MODELING OF ASPIRIN FLOATING TABLETS USING DDSOLVER

Aspirin has low solubility in water therefore, dissolution is a rate limiting step for absorption. Floating tablet formulation is designed to improve the bioavailability of aspirin. The objective of this study was to determine in vitro dissolution study of aspirin floating tablet release kinetics model. The floating tablets were prepared by a direct compression method using Methocel K4M CR, NaHCO3, Ethocel, Aerosil, and dicalcium phospate anhydrous as excipients. Tablets were evaluated by different parameters such as physicochemical properties, floating lag time (Flag time), total floating time, and dissolution. The result showed that the tablet mass has good flow properties of 13.54 g/sec. Aspirin floating tablets had a weight uniformity (CV=1.45%), good hardness (6.42kg), and low friability (0.158%). The tablet has a short Flag time of 25.16 sec and long floating time of 8 hours. Dissolution data were evaluated using DDSolver conducted by (1) Statistical parameters: R2adjusted, AIC, MSC; (2) Visual goodness of fit (GOF). The results showed that aspirin floating tablets release kinetics followed the Korsmeyer-Peppas model. Aspirin release occurs through the mechanism of anomalous transport which combines Fickian diffusion and polymer relaxation. Key words: aspirin floating tablet, DDSolver, modeling of drug release

Radiation Synthesis of Stimuli Responsive Micro-porous Hydrogels for Controlled Drug Release of Aspirin

A novel thermo- and pH-sensitive hydrogels based on N-isopropylacrylamide and containing acrylic acid (mono carboxylic), oxalic acid (oxalic) (dicarboxylic), and citric acid (citric) (tricarboxylic) have been prepared using mutual radiation technique. Fourier transform infrared spectroscopy was used to identify the structure of the prepared hydrogels. The surface morphology of the hydrogels was observed using scanning electron microscopy. Swelling percent found to be decreased with the increase in the temperature. It was proved that the prepared hydrogels were extremely sensitive to both temperature and pH. The possibility of using such hydrogels as a drug carrier was estimated using acetylsalicylic acid (aspirin) as a model drug. The drug release in pH 6.8 was more than that in pH 2. Owing to its considerable drug release, good swelling, it might be useful for its application as a drug delivery system in small intestine.

Fabrication of mesoporous silica nanospheres with radially oriented mesochannels by microemulsion templating for adsorption and controlled release of aspirin

The MSN spheres with narrow size distribution and radially oriented mesoporous channels were prepared using an O/W microemulsion system, consisting of CTAB (or PVP), ethanol, cyclohexane and water as template.

Synthesis of aspirin-loaded polymer-silica composites and their release characteristics.

This study describes a novel approach to the synthesis of polymer-drug-silica nanocomposites via encapsulation/isolation of drug molecules, introduced into the polymer matrix by the silica gel. For the first time, tetraethoxysilane (TEOS) gelation in the vapor phase of the acidic catalyst is presented as an efficient method to enter the silica gel nanoparticles into the polymer-aspirin conjugate. The conducted studies reveal that the internal structure of the polymer carrier is significantly reorganized after the embedding of aspirin molecules and the silica gel. The total porosity of the polymer-drug-silica nanocomposites and the molecular structure of the silica gel embedded in the system strongly depend on the conditions of the silica source transformation. Additionally, the release of the drug was fine-tuned by adapting the conditions of hydrolysis and condensation of the silica gel precursor. Finally, to prove the usefulness of the proposed synthesis, the controlled release of aspirin from the polymer-drug-silica nanocomposites is demonstrated.

Palygorskite polypyrrole nanocomposite: A new platform for electrically tunable drug delivery

A clay polymer nanocomposite (CPN) based on aspirin-loaded palygorskite (Pal) modified polypyrrole (PPy) was prepared by in situ electropolymerization of pyrrole monomer in the presence of Pal as the modifier and aspirin as the drug source. This drug-loading approach was simple and convenient, since colloid templates such as polystyrene microspheres used in conventional drug-loading system were not needed. The resulting CPN was characterized by TEM, XRD, cyclic voltammetry (CV), chronocoulometry, electrochemical impedance spectroscopy (EIS) and FTIR. The CPN was used as a new platform for aspirin delivery, which could significantly enhance aspirin loading capacity of the system and control aspirin release by external electrical stimulus. The results indicated that the proposed novel drug-delivery system might be promising as an implantable device where drug release could be electrically tuned according to the patient's requirement.

Promising psyllium-based composite containing TiO2 nanoparticles as aspirin-carrier matrix

Composite nanomaterials represent a new trend in the biomedical field. Coupling inorganic/organic constituents with non-toxicity/biocompatibility properties leads to develop the new systems having special characteristics that can be used in various bio-applications. This paper describes the preparation and characterization of psyllium-based composites containing TiO2 nanoparticles in order to develop new therapeutic strategies for aspirin drug delivery. The structural characteristics of obtained materials were investigated by FTIR spectroscopy. The UV–vis spectrophotometric analysis was performed to evaluate the aspirin release behavior under different pH conditions at 37°C. Combining psyllium (as an excellent source of fiber) with TiO2 inorganic unit (as vehicle of aspirin) it was found that polymeric-TiO2 networks have promising potential for controlled aspirin release as therapeutic agent.

A Study of Controlled Release of Aspirin by Mesoporous SBA-15

Mesoporous SBA-15 materials with high surface area were synthesized using hydrothermal method. These materials have large surface area, therefore good adsorber, besides the large pores offer sites for drug loading. The synthesized mesoporous materials were loaded with aspirin. Then controlled release of aspirin by the materials was studied in phosphate buffer system using UV- Visible spectrophotometer to monitor the concentration. The prepared samples were characterized by XRD, Nitrogen adsorption-desorption studies, TEM, IR and TGA. The benign nature of the SBA-15 materials makes it an ideal carrier for aspirin and facilitates the controlled release of the drug.

Improvement of histocompatibility of silk fibroin/polyurethane membrane with controlled release of aspirin

ABSTRACTThe histocompatibility of polyurethane (PU) modified by superfine silk‐fibroin (SF) powder (1 : 1) with different dosage of aspirin to determine the best dosage for histocompatibility was investigated. Aspirin powder was incorporated into SF–PU (1 : 1) blend mixture at doses of 0%, 5%, or 10% (w/w). The influence of different doses of aspirin on histocompatibility of the hybrid material was studied by using morphology examination, infrared spectroscopy, in vitro drug release study, and in vivo tests including an acute toxicity test, an assessment of local reaction in the muscle, hematological examination, and histological examination. SF–PU (50 : 50) blend film had superior performance over the polytetrafluoroethylene (e‐PTFE) film in terms of histocompatibility, and the anti‐inflammatory/anti‐platelet effects were improved after integration with limited doses of aspirin to yield a valuable drug release vascular graft. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40580.

Synthesis of pH-Sensitive CMC /Chitosan Hydrogels by Gamma Irradiation

Gamma irradiation was used with different dosages to prepare hydrogels from carboxymethyl cellulose (CMC) and chitosan (CHI) with different ratios, in presence of different methylene bisacrylamide (MBA) concentrations as a crosslinking agent. The hydrogels were characterized by FT-IR spectroscopy which confirmed complexation between carboxylic group in CMC and amino group in CHI. The swelling behavior in different buffers of different pH values was also studied. The results indicated the formation of network structure of pH-sensitive hydrogels. The CMC/CHI hydrogels were evaluated for the possible use in drug delivery field, in which the release profile of aspirin, as a drug model, was investigated. Scanning electron microscopy was carried out before and after aspirin release proving the drug release.

Insights and relative effect of aspirin, naproxen and ibuprofen containing hydrogels: From design to performance as a functional dual capacity restorative material and build in free radical defense: <i>In-vitro</i> studies

Restorative materials in the new era aim to be “bio-active” and long-lasting. It has been suggested that the anti-inflammatory activity of some non-steroidal anti-inflammatory drugs (NSAIDs) may be partly due to their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as to inhibit the respiratory burst of neutrophils triggered by various activating agents. As a part of our continuous interest of developing functional dual action restorative materials capable of being “bio-active” and long-lasting, we design and evaluate novel chitosan hydrogels containing krill oil (antioxidant containing material), naproxen, ibuprofen (non steroidal anti-inflammatory medication), aspirin (pain relieve medication and free radical scavengers) and combinations thereof (chitosan-H-krill oil, chitosan-H-krill oil-aspirin and chitosan-H-naproxen, chitosan-H-naproxen-krill oil, chitosan-H-krill oil-ibuprofen and chitosan-H-ibuprofen) as functional additive prototypes for further development of “dual function restorative materials”; secondly, determine their effect on the dentin bond strength of a composite and thirdly, evaluate the capability of newly designed hydrogels to play an integral role of “build in” free radical defense mechanism by using BSA solubility as a “molecular prototype” of the site of free radical attack in vitro. Materials and Methods: The above mentioned hydrogels were prepared by dispersion of the corresponding component in glycerol and acetic acid with the addition of chitosan gelling agent. The surface morphology (SEM), release behaviors (physiological pH and also in acidic conditions), stability of the therapeutic agent-antioxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were also evaluated. Results: The release of aspirin, ibuprofen and naproxen confers the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Neither the release of aspirin, ibuprofen or naproxen nor the antioxidant stability was affected by storage over a 6- month period. The hydrogel formulations have a uniform distribution of drug content, homogenous texture and yellow color (SEM study). All chitosan dentin treated hydrogels gave significantly (P P in vitro conditions. Conclusion: The added benefits of the chitosan treated hydrogels involved positive influence on the aspirin, ibuprofen and naproxen release, increased dentin bond strength as well as demonstrated in vitro “build in” free radical defense mechanism, therefore acting as a “proof of concept” for the functional multi-dimentional restorative materials with the build in free radical defense mechanism.