Добавил:
kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:
Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5361_Библиотеки_им_академика_М_И_Перельмана.pdf
Скачиваний:
0
Добавлен:
31.08.2026
Размер:
23 Мб
Скачать
10 Composites forDrug-Eluting Devices: Emerging Biomedical Applications
275
10.4.2.3 Surface Grafting
Surface grafting involves attaching functional groups or polymers onto the surface of drug-eluting composites. This technique can be utilized to introduce hydrophilic or hydrophobic moieties, altering the surface energy and modifying interactions with biological tissues. Surface grafting is valuable for tailoring the release kinetics of therapeutic agents and improving the overall performance of drug-eluting devices [154].
10.4.2.4 Dip Coating
Dip coating presents itself as a foundational and easily implementable method for coating stents with drugs and polymers. Its uncomplicated nature, coupled with the ability to customize the coating composition, makes it a valuable tool in the arsenal of techniques available for researchers and clinicians involved in the advancement of drug-eluting stent technologies. It stands out as a fundamental and straightfor­ward technique in coating applications for drug-eluting stents, notable for its sim­plicity and minimal equipment requirements. This method involves immersing the stent in a solution containing typical drugs and/or polymers dissolved in a solvent. The coated stent is then left to undergo a drying process, facilitated by either air exposure or the controlled environment of an oven, as depicted in Fig.10.3 [155]. The inherent simplicity of dip coating renders it an accessible and practical choice, particularly in scenarios where extensive machinery or prolonged processing times are not feasible.
The versatility of dip coating is evident in the varied combinations of polymers, drugs, and their concentrations that can be employed during the process. Researchers have the exibility to tailor the coating composition based on the specic require­ments of their study. For instance, a study by Jang etal. utilized dip coating to apply
Fig. 10.3 Schematics of dip coating [155]
276
A. K. Gupta et al.
curcumin onto stents, offering the option to coat them with either a low or high dose of the therapeutic agent, all without incorporating any additional polymer. This adaptability in polymer and drug selection, coupled with the simplicity of the dip coating technique, contributes to its appeal in the development of drug-eluting stents [59, 155].
10.4.2.5 Spray Coating System
Spray coating emerges as a valuable technique in the manufacturing of DES, pre­senting versatility in coating designs and scalability for mass production. Despite the challenges in evaluating this technology, its role in cardiac research remains pivotal, contributing to advancements in drug-eluting stent technologies. Spray coating, encompassing techniques such as ultrasonic atomization, electrodynamic jetting, and airbrush coating, stands out as a prominent method for the application of polymer and drug solutions onto stent surfaces. Employing devices that spray these solutions onto the stent using various solvents ensures a uniform and consis­tent deposit of drug-release layers. This technique is versatile and allows for higher variability in coating designs, enhancing the optimization of the release prole. The system schematic presented in Fig. 10.4 illustrates the spray-coating process, emphasizing its adaptability and ability to produce a logarithmic release curve. This curve typically exhibits a burst release, attributed to the initial presence of the drug at the stent’s boundary layer, followed by a slower, sustained release for long-term therapeutic effects [156].
Spray-coating techniques play a pivotal role in manufacturing drug-eluting stents (DES), particularly in cardiac research. The method is known for its straightfor­wardness in scaling up the production of consistently coated stents in high volumes.
Fig. 10.4 Illustration of spray coating system [156]
10 Composites forDrug-Eluting Devices: Emerging Biomedical Applications
277
However, evaluating this technology poses challenges due to the multitude of vari­ables involved, making broad comparisons between individual designs nearly impractical [156]. Understanding the mechanism of drug delivery is crucial for selecting the appropriate drug and achieving a time-ordered release. Polymeric sys­tems serve as efcient drug carriers due to their ability to provide a framework for controlled drug release and protect the drug from degradation before it exerts its therapeutic effects. The mechanism of drug release from the polymer substrate can be categorized into physical and chemical mechanisms. The physical mechanism involves drug release through permanent polymer layers, dissolution or degradation of the polymer, permeation pressure, and ion exchange processes. On the other hand, the chemical mechanism results from the breakage of covalent bonds due to chemical or enzymatic degradation [7]. The evolution of drug-polymer systems has transitioned from nonbiodegradable to biodegradable polymers, where the latter has become a signicant player in drug-eluting systems. The drug diffusion process in nonbiodegradable polymers was controlled by the concentration gradient. In con­trast, biodegradable polymers offer three major release mechanisms based on the type of polymer: diffusion (for permanent polymers), swelling, and degradation. These mechanisms highlight the versatility and adaptability of polymeric systems in achieving controlled and effective drug delivery [157].
10.4.2.6 Electrotreated Coating
Electrotreated coating techniques represent a novel approach in stent technology, introducing electrical stimulus to assist in the deposition of drugs or polymers onto stent surfaces. One notable method is electrophoretic deposition (EPD), which employs an electric eld, either in a dry or salted environment, to attract charged particles onto the stent surface, forming a drug-release layer. The electrophoretic deposition (EPD) apparatus, as illustrated in Fig.10.5a, provides insight into the technique’s application [158]. In electrostatic dry powder deposition (Fig.10.5b), researchers coated stents with sirolimus-loaded PEVA and PBMA microparticles, comparing the release proles with a commercially available Cypher stent. This approach exhibited a burst release of 50% in 3days, surpassing the 35% release of
Fig. 10.5 Illustration of (a) electrophoretic deposition (EPD) [157] and (b) electrostatic dry pow­der deposition [159]
278
A. K. Gupta et al.
the Cypher stent. Additionally, it achieved a total release of 100% after 25days, exceeding the Cypher stent’s 85% release [159]. Electrotreated coating techniques, particularly EPD, offer innovative ways to enhance drug release proles in stents. However, the safety and efcacy of electrotreated stents remain to be evaluated in clinical settings. Meanwhile, plasma-treated coatings show promise in strengthen­ing drug-release layers, but further research is needed to validate their effectiveness in DES applications.
In another study by Liu etal., a DES was designed using multiple techniques. They deposited N-nitrosomelatonin (NOMela)-loaded PLGA nanoparticles onto SS 316L stents using EPD and then applied dip coating to create a collagen diffusion barrier [160]. Release proles of hydrophobic and hydrophilic drugs were studied after immersing the stent in PBS, revealing a burst release of 50–70% in 24hours, with an additional 20% release between days 2 and 14 [160]. While the integration of electrical stimulus in stent coating presents an exciting development, the safety and efcacy of electro treated stents have yet to be evaluated in clinical models, limited to noninferiority animal models. Moving to plasma-treated coatings, researchers have recently explored the inclusion of plasma treatments to enhance chemical bonds in drug-release layers through polymer cross-linking. This tech­nique involves exposing the stent surface to a gaseous plasma beam with varying exposure times. In a study led by Hagiwara, silicon wafers coated with curcumin­loaded PEVA were plasma-treated with argon, oxygen, and nitrogen. Results showed that highly treated samples released signicantly less drug over time com­pared to untreated stents, demonstrating the potential of plasma treatments as a release platform for DES [157].
10.4.2.7 Nanocoating andNanoparticle Incorporation
Nanocoatings and the incorporation of nanoparticles on the surface of drug-eluting composites offer unique opportunities for enhancing properties. Nanoscale materi­als can provide specic functionalities, such as improved lubrication or targeted drug delivery. Nanoparticles can be embedded within coatings or directly into the composite matrix to impart desired surface characteristics, inuencing wear resis­tance and drug release [161, 162].
10.4.2.8 Polymer Blending andComposite Formation
Mixing different polymers or composite materials during the fabrication process can lead to the creation of drug-eluting composites with tailored surface properties. By blending polymers with complementary characteristics, such as one providing structural integrity and another offering controlled drug release, researchers can achieve synergistic effects to enhance overall performance [163].
10 Composites forDrug-Eluting Devices: Emerging Biomedical Applications
10.4.2.9 Microfabrication Techniques
Microfabrication techniques, such as micromolding or photolithography, can be employed to create micro-patterned surfaces on drug-eluting composites. Microfabrication enhances surface topography and can be utilized to control drug release proles. This technique allows for precise engineering of surface features, inuencing wear and friction properties as well as therapeutic agent release [164].
10.4.2.10 Surface Roughness Control
Controlling the surface roughness of drug-eluting composites can be achieved through techniques such as mechanical polishing, acid etching, or laser ablation [165]. Optimizing surface roughness [166] is crucial for inuencing wear resis­tance, improving tissue integration, and reducing friction during device implanta­tion [167].
10.4.2.11 Incorporation ofSmart Materials
Integrating smart materials, such as shape-memory polymers or materials respon­sive to external stimuli, into the surface of drug-eluting composites allows for dynamic adjustments in response to environmental changes. These materials can enhance adaptability and functionality, improving wear resistance and drug release control. A combination of these techniques can be employed in a synergistic manner to enhance the surface properties of drug-eluting composites. Surface engineering plays a pivotal role in tailoring the tribological properties and drug release charac­teristics, ultimately contributing to the improved performance and efcacy of these biomedical devices in various clinical applications [168, 169].
279
10.5 Characterizations ofDrug-Eluting Composite
10.5.1 Methods forCharacterizing Composite Materials
Characterizing drug-eluting composites is essential to understanding their perfor­mance, ensuring their safety, and optimizing their efcacy in biomedical applica­tions. Various characterization methods are employed to assess different aspects of these composites, ranging from their structural integrity to drug release kinetics. The following discusses various methods used to characterize the properties of drug-eluting composites, as mentioned in Table10.5.
Comprehensive characterization methods are essential to thoroughly understand the structural, chemical, mechanical, and biological aspects of these composite
280
A. K. Gupta et al.
[174]
Additional insights (from your
data) References
Composite porosity affects drug
Pore size, distribution of
[175]
loading and release rate.
FTIR spectra can identify
therapeutic agents, matrix
homogeneity
Molecular interactions,
[176]
potential drug-matrix
incompatibilities.
Stiffness can affect drug release
kinetics.
potential degradation
products
Suitability for specic
applications, impact
[177]
Wettability inuences cell
resistance
[178]
adhesion and drug diffusion.
Release kinetics need to be
tailored for specic therapeutic
biological uids and
tissues
Release rate prole, drug
stability within the
[179]
goals.
Biocompatibility is crucial for
composite
[180]
long-term implant success.
Imaging can reveal unexpected
potential inammatory
response
Drug targeting, implant
off-target effects.
degradation invivo
[181]
Histology can differentiate
Biomaterial integration,
between sterile and foreign body
reactions.
tissue healing around the
implant
Surface morphology
and microstructure
Functional groups in
matrix and agents
Strength, stiffness,
elasticity
Wettability Interaction with
microscope (SEM)
Fourier transform
infrared spectroscopy
(FTIR)
Tensile, compression,
exural tests
Contact angle
composition analysis
Sr.
no. Properties Technique Focus Information gained
Table 10.5 Methods for characterizing composite materials for characterizations of drug-eluting composites
1 Structural analysis Scanning electron
2 Chemical
properties
3 Mechanical
4 Surface
Quantication of
released drugs
measurement
High-performance liquid
chromatography (HPLC)
Cell viability assays Cytotoxicity Impact on cell health,
characteristics
analysis
5 Release kinetics
6 Biological
persistence of
compatibility
7 In vivo imaging MRI, PET Distribution and
composites
Tissue compatibility,
inammatory response
Histopathological
analysis
response assessment
8 Inammatory
10 Composites forDrug-Eluting Devices: Emerging Biomedical Applications
281
[174, 176]
Stability studies inform storage
and handling guidelines.
[59]
Shelf life, drug efcacy
within the composite
Swelling can affect drug
[182]
Electrochemical properties
release and device
functionality.
Biomaterial degradation,
[183]
inuence long-term safety and
efcacy.
Thermal stability ensures device
impact on surrounding
tissues
Glass transition
integrity during sterilization and
temperature, drug release
implantation.
behavior
time
Material response to
physiological
conditions
Stability studies Drug degradation over
Weight and size changes,
matrix integrity
analysis
studies
9 Drug stability
10 Swelling and erosion
tissue interaction
EIS Corrosion resistance,
analysis
11 Electrochemical
response to
temperature changes
12 Thermal analysis DSC, TGA Thermal stability,
282
A. K. Gupta et al.
materials. In the context of drug-eluting composites, where the integration of drugs or therapeutic agents within a matrix is crucial, precise structural analysis becomes imperative. Techniques such as scanning electron microscopy (SEM) [170] enable researchers to examine the surface morphology and microstructure, providing insights into pore size, the distribution of therapeutic agents, and matrix homogene­ity [171]. This information is invaluable for optimizing drug loading, release kinet­ics, and overall performance. Chemical composition analysis, facilitated by methods like Fourier Transform Infrared Spectroscopy (FTIR), helps unravel molecular interactions within the composite [172]. FTIR identies functional groups in the matrix and drug components, offering insights into potential degradation products and ensuring compatibility between drugs and polymers. The mechanical properties of drug-eluting composites, assessed through tensile, compression, and exural tests, are critical for determining the suitability of these materials for specic appli­cations. For instance, stiffness can inuence drug release kinetics, and understand­ing these mechanical aspects aids in tailoring the composite for optimal performance. Overall, a multidimensional characterization approach is essential in elucidating the intricate features of drug-eluting composites, paving the way for the development of efcient and tailored drug delivery systems in biomedical applications. Table10.6 shows the advantages and disadvantages of various characterization methods [173].
10.5.1.1 Structural andChemical Analysis
Scanning electron microscopy (SEM) acts as a high-powered zoom lens, revealing the surface topography and internal architecture of the composite. This detailed view allows researchers to assess pore size, distribution of therapeutic agents within the matrix, and overall homogeneity of the material. On the other hand, Fourier transform infrared spectroscopy (FTIR) shines a light on the chemical landscape. By identifying functional groups within the matrix and therapeutic agents, FTIR provides insights into the molecular interactions that govern the composite’s stabil­ity and drug release behavior [185].
10.5.1.2 Mechanical Properties
The mechanical integrity of a drug-eluting composite is paramount for its success­ful function. Tensile, compression, and exural tests subject the material to con­trolled forces, revealing its strength, stiffness, and elasticity. This information dictates the suitability of the composite for specic applications, ensuring it can withstand the physiological demands of the target tissue without compromising structural integrity or drug release kinetics [186].
10 Composites forDrug-Eluting Devices: Emerging Biomedical Applications
Table 10.6 The advantages and limitations of various characterization techniques [173, 184]
Name of characterization techniques Advantages Disadvantages
Scanning electronic microscopy (SEM)
Transmission electron microscopy (TEM)
Atomic force microscopy (AFM)
Magnetic resonance force microscopy (MRFM)
X-ray diffraction (XRD)
It gives a 3D and high-resolution photograph of nanomaterials. It gives quick and reliable results. It provides information on the specimen’s surface and composition. It has a resolution power between 1 and 20nm.
It provides incredibly strong magnication and resolution. It provides knowledge about elements and complex structures. It gives excellent detailed and quality images. It has a resolution power of
0.17nm. It works under liquid, vacuum, and air.
It can be applied to the living system. It gives sure information about height. It has a vertical resolution of up to 0.1nm.
It modied the lesion characterization. No ionization radiation. It excellently differentiates normal tissues. It has a vertical resolution of up to 0.1nm.
It is cost-effective and convenient. Scientists extensively utilize this technique to nd out the crystalline structure of nanomaterials. It is a very effective technique for the analysis of phases.
These techniques are very large and expensive. Trained people are required to operate the SEM. SEMS can only be used on solid samples. The images are black and white.
It gives black-and-white photographs . It requires special housing and maintenance. They are expensive and large.
It has a limited vertical and magnication range. It can break the sample or tip. It has a limited scanning speed.
Required higher scanning time. It was highly expensive. Because of the pulse generation, it is noisier.
X-rays do not effectively interact with lighter elements. Its intensity is ten times less than the electron diffraction.
283
10.5.1.3 Surface Characteristics
Contact angle measurements focus on the wettability of drug-eluting composites, shedding light on their interaction with biological uids and tissues. Wettability is a crucial factor inuencing cell adhesion and drug diffusion within the physiological environment, thereby inuencing the overall biocompatibility of the compos­ite [187].
284
A. K. Gupta et al.
10.5.1.4 Release Kinetics Analysis
High-performance liquid chromatography (HPLC) is employed to quantify released drugs, offering a detailed understanding of the release rate prole and drug stability within the composite. Tailoring release kinetics based on therapeutic goals is essen­tial, and HPLC serves as a key method for achieving this customization [188]. To quantitatively determine the drug loaded in the matrices, the solvents can be extracted, collected by ltration under efciently designed vacuum chambers [189,
190], and then subjected to HPLC analysis.
10.5.1.5 Biological Compatibility
Cell viability assays assess the cytotoxicity of drug-eluting composites, providing information on their impact on cell health and the potential for an inammatory response. Biocompatibility is a critical factor for the long-term success of implants, making cell viability assays integral to the assessment of these materials [191].
10.5.1.6 In Vivo Imaging andInammatory Response Assessment
In vivo imaging techniques such as MRI and PET allow researchers to study the distribution and persistence of drug-eluting composites within the body. Histopathological analysis further assesses tissue compatibility and inammatory responses, crucial aspects for understanding biomaterial integration and tissue heal­ing around the implant [192].
10.5.1.7 Other Analyses
The other methods for drug stability analysis, swelling and erosion studies, electro­chemical analysis, and thermal analysis are also discussed by various researchers [193195]. Stability studies inform guidelines on storage and handling while swell­ing and erosion studies reveal material responses to physiological conditions. Electrochemical and thermal analyses provide insights into corrosion resistance, tissue interaction, and thermal stability, ensuring the long-term safety and efcacy of drug-eluting composite materials. Differential Scanning Calorimetry (DSC) or Thermogravimetric Analysis (TGA) techniques help evaluate the thermal stability of drug-eluting composites and provide insights into their response to temperature changes [183]. By employing these characterization methods, researchers gain a comprehensive understanding of the structural, chemical, mechanical, and biologi­cal properties of drug-eluting composites. This knowledge is crucial for optimizing the design, fabrication, and performance of these materials in diverse biomedical applications [196].