Hemocompatibility of Layer-by-Layer Hyaluronic Acid/Heparin Nanostructure Coating on Stainless Steel for Cardiovascular Stents and its Use for Drug Delivery

2006 ◽  
Vol 6 (9) ◽  
pp. 3163-3170 ◽  
Author(s):  
Li-Ying Huang ◽  
Ming-Chien Yang

In order to develop drug-eluting cardiovascular stents, stainless steel (SUS316L) sheets were coated with hyaluronic acid (HA) and heparin (HEP), and their in vitro characteristics and drug release pattern were investigated. The surface of stainless steel (SS) was treated with nitric acid and followed by anchoring aminotrimethoxysilane (ATMS), then a nanolayer of HA was covalently immobilized onto the surface. Heparin was then covalently bonded to the HA-immobilized SS substrate. After repeating 1 to 5 cycles, 1 to 5 layers polyelectrolyte complex (PEC) nanobrush of HA/HEP were resulted with the thickness ranging from 280 to 630 nm (measured with ellipsometry). A model drug (sirolimus) was loaded in the HA/HEP layers at a density ranging from 1.02 to 3.12 μg/cm2. The SS-ATMS-HA-HEP substrates were evidenced by X-ray photoelectron spectroscope (XPS), contact angle, and AFM measurement. The effect of this surface modification on the coagulation time of the resulting SS substrates was investigated. The results show that the multilayer HA/HEP stainless steel would exhibit higher anticoagulant activity than pure SS substrates. In addition, the results of the in vitro drug delivery study showed that release of sirolimus from the 5-layer-HA-HEP stainless steel was able to maintain more than 30 days. Thus layer-by-layer HA/HEP PEC can improve the hemocompatibility of SS surface and control the drug released rate by multiple layers of HA/HEP PEC. These results indicate that the multi-layer HA/HEP PEC coated stainless steel would be suitable for drug eluting stents.

Author(s):  
Irene Carmagnola ◽  
Tiziana Nardo ◽  
Francesca Boccafoschi ◽  
Valeria Chiono

The stainless steel (SS) stents have been used in clinics since 1994. However, typical drawbacks are restenosis and thrombus formation due to limited endothelialisation and hemocompatibility. Surface modification is a smart strategy to enhance antithrombogenicity by promoting endothelialisation. In this work, the layer-by-layer (LbL) technique was applied for coating SS model substrates, after surface priming by functionalisation with 3-aminopropyl triethoxysilane (APTES). A LbL coating made of 14 layers of poly(styrene sulfonate)/poly(diallyldimethylammonium chloride) and heparin as last layer was deposited. FTIR-ATR analysis and contact angle measurements showed that LbL was an effective method to prepare nanostructured coatings. XPS analysis and colorimetric assay employing 1,9-dimethylmethylene blue dye to detect -COOH groups confirmed the successful polyelectrolyte deposition on the coated samples. Preliminary in vitro cell tests, using whole blood and human platelets, were performed to evaluate how surface modification affects platelet activation. Results showed that SS and SS-APTES surfaces induced platelet activation, as indicated by platelet spreading and filopodia formation. After surface modification by LbL coating, the platelets assumed a round shape and no fibrin nets were detected. Data demonstrated that LbL coating is a promising technique to fabricate antithrombogenic surface.


Author(s):  
Sai S. Sagiri ◽  
Suraj K. Nayak ◽  
S. Lakshmi ◽  
Kunal Pal

In recent years, the use of biopolymeric nanoparticles as vehicles for drug delivery has increased exponentially. In the present study, chitosan and gelatin nanoparticles were prepared by ionic gelation and desolvation methods, respectively. Salicylic acid was used as the model drug. The nanoparticles were characterized using SEM, XRD analysis and FTIR spectrophotometric studies. In vitro drug release experiments were carried out to understand the mechanism of drug release. SEM micrographs showed the formation of spherical nanoparticles. XRD studies indicated a higher crystalline nature of the chitosan nanoparticles as compared to the gelatin nanoparticles. FTIR studies indicated the presence of salicylic acid within the drug- loaded nanoparticles. Drug release studies indicated that the developed nanoparticles may be used as carriers for various bioactive agents.


Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2570 ◽  
Author(s):  
Inés Serrano-Sevilla ◽  
Álvaro Artiga ◽  
Scott G. Mitchell ◽  
Laura De Matteis ◽  
Jesús M. de la Fuente

Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.


2013 ◽  
Vol 10 (84) ◽  
pp. 20130070 ◽  
Author(s):  
Haiyong Ao ◽  
Youtao Xie ◽  
Honglue Tan ◽  
Shengbing Yang ◽  
Kai Li ◽  
...  

Layer-by-layer (LBL) self-assembly technique has been proved to be a highly effective method to immobilize the main components of the extracellular matrix such as collagen and hyaluronic acid on titanium-based implants and form a polyelectrolyte multilayer (PEM) film by electrostatic interaction. However, the formed PEM film is unstable in the physiological environment and affects the long-time effectiveness of PEM film. In this study, a modified LBL technology has been developed to fabricate a stable collagen/hyaluronic acid (Col/HA) PEM film on titanium coating (TC) by introducing covalent immobilization. Scanning electron microscopy, diffuse reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the PEM film. Results of Sirius red staining demonstrated that the chemical stability of PEM film was greatly improved by covalent cross-linking. Cell culture assays further illustrated that the functions of human mesenchymal stem cells, such as attachment, spreading, proliferation and differentiation, were obviously enhanced by the covalently immobilized Col/HA PEM on TCs compared with the absorbed Col/HA PEM. The improved stability and biological properties of the Col/HA PEM covalently immobilized TC may be beneficial to the early osseointegration of the implants.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 726
Author(s):  
Kuldeep Kumar Bansal ◽  
Ezgi Özliseli ◽  
Gaurav Kumar Saraogi ◽  
Jessica M. Rosenholm

Biodegradable polymers from renewable resources have attracted much attention in recent years within the biomedical field. Lately, poly(δ-decalactone) based copolymer micelles have emerged as a potential drug delivery carrier material as a sustainable alternative to fossil-based polymers. However, their intracellular drug delivery potential is not yet investigated and therefore, in this work, we report on the synthesis and cellular uptake efficiency of poly(δ-decalactone) based micelles with or without a targeting ligand. Folic acid was chosen as a model targeting ligand and Rhodamine B as a fluorescent tracer to demonstrate the straightforward functionalisation aspect of copolymers. The synthesis of block copolymers was accomplished by a combination of facile ring-opening polymerisation and click chemistry to retain the structure uniformity. The presence of folic acid on the surface of micelles with diameter ~150 nm upsurge the uptake efficiency by 1.6 fold on folate receptor overexpressing MDA-MB-231 cells indicating the attainment of targeting using ligand functionality. The drug delivery capability of these carriers was ascertained by using docetaxel as a model drug, whereby the in vitro cytotoxicity of the drug was significantly increased after incorporation in micelles 48 h post incubation. We have also investigated the possible endocytosis route of non-targeted micelles and found that caveolae-mediated endocytosis was the preferred route of uptake. This work strengthens the prospect of using novel bio-based poly(δ-decalactone) micelles as efficient multifunctional drug delivery nanocarriers towards medical applications.


2010 ◽  
Vol 11 (3) ◽  
pp. 713-720 ◽  
Author(s):  
Anna Szarpak ◽  
Di Cui ◽  
Frédéric Dubreuil ◽  
Bruno G. De Geest ◽  
Liesbeth J. De Cock ◽  
...  

2008 ◽  
Vol 14 (S3) ◽  
pp. 35-36 ◽  
Author(s):  
J. Nunes ◽  
A.P. Piedade ◽  
C.B. Duarte ◽  
M.T. Vieira

When compared with conventional bare metal stents, such as 316L stainless steel, the introduction of drug-eluting stents can promote reduction in the incidence of in-stent restenosis. However, the chemical discrepancy between the metallic stent and the polymeric material that acts as the reservoir for the drug is responsible for some problems during the cardiovascular surgery. Besides the research work aiming at the development of new bulk alloys for stent production, focus as been also directed to the surface modification of these devices. However, the use of functional graded coatings (FGC), i.e., coatings with a gradient of chemical composition between the substrate and the outmost layer, has never been reported in devices for cardiovascular surgery.


2005 ◽  
Vol 288-289 ◽  
pp. 129-132 ◽  
Author(s):  
Ling Chen ◽  
Xiao Xi Li ◽  
Lin Li ◽  
Bing Li

Colon-targeting drug delivery systems (CDDSs) are employed to improve the bioavailability of protein and peptide drugs through the oral route. So it is important to prepare the drug carriers for oral CDDS. In this study, the Enzyme-Resistant starch (RS) was studied for use as a vehicle in oral colon-targeting drug delivery. The characteristics of RS powders were investigated by X-ray diffraction, polarizing microscopy, DSC and SEM, and their film were examined by enzymatic digestion test. The results showed that RS could be a promising film-former for pharmaceutical coatings, having good stability to enzymatic digestion. Furthermore, a novel peroral formulation using RS coating and bovine serum albumin as a model drug was studied for colon-specific drug delivery in vitro. Drug release studies have shown that RS coating could delivery the drug to the colon and the release rate in simulated colonic fluids was dependent on the biodegradation of RS and its coatings. It is indicated that the RS coated tablet is a potential system for oral CDDS.


1970 ◽  
Vol 1 (1) ◽  
pp. 25-28
Author(s):  
B Vijaya Kumar ◽  
B Nagaraj ◽  
B Agaiah ◽  
D Rambhau

The objective of this research work was to prepare a chrono modulated delivery system to meet chronopharmacological needs of asthma. In this study theophylline was selected as a model drug. To meet this objective we considered an initial lag phase of release for 3-5 hrs and later a rapid (surge) release phase. To achieve surge release a rapidly releasing core tablet of theophylline was developed by admixing theophylline with effervescent granules and super disintegrants. The lag phase in release was achieved by coating the EV core tablets with release retarding polymer EUDRAGIT RS-100 containing HPMC, further over coated with enteric polymer CAP. The results indicate that a rapidly releasing EV tablet of theophylline cab be developed which when coated with the polymers a lag phase of 2 hrs was achievable followed by a surge release. Key Words: Theophylline, Chrono Modulated Drug Delivery, Asthma. doi:10.3329/sjps.v1i1.1782 S. J. Pharm. Sci. 1(1&2): 25-28


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