Biomedical Applications In Drug Delivery Research Articles

Bubble oscillations at low frequency ultrasound for biological applications

Bubbles oscillating in the presence of ultrasound is commonly employed in biomedical applications for drug delivery, ultrasound enhanced thrombolysis, and the transport and manipulation of cells. This is possible because bubbles tend to interact with the ultrasound to undergo periodic shape changes known as shape-mode oscillation, concomitant with the generation of liquid agitation or streaming. This phenomenon is examined both experimentally and theoretically on a single bubble at a frequency of (45 ± 1) kHz. Effects of ultrasonic frequency and power on the flowfield were explored. Experiments revealed different trends in the development of liquid streaming velocities at different acoustic forcing conditions (5.53, 6.80 and 7.02 Vpp), with lowest (0.5 mm/s) and highest (1.1 mm/s) values of time-averaged mean streaming velocity occurring at 6.80 Vpp and 7.02 Vpp, respectively. Simulations captured the simultaneous evolution of bubble-shapes that helped create flow vortices in the liquid surrounding the bubble. These vortices collectively responsible in generating signature patterns in the liquid for a dominant shape-mode of the bubble, and could also generate localised shear stresses for practical application. The velocity and pressure profiles in the liquid around the bubble confirmed the connection of the applied and reflected soundwaves in driving this phenomenon.

Biological Properties of Arginine-rich Peptides and their Application in Cargo Delivery to Cancer

Cell-penetrating peptides (CPPs) comprise short peptides of fewer than 30 amino acids, which are rich in arginine (Arg) or lysine (Lys). CPPs have attracted interest in the delivery of various cargos, such as drugs, nucleic acids, and other macromolecules over the last 30 years. Among all types of CPPs, arginine-rich CPPs exhibit higher transmembrane efficiency due to bidentate bonding between their guanidinium groups and negatively charged cellular components. Besides, endosome escape can be induced by arginine-rich CPPs to protect cargo from lysosome-dependent degradation. Here we summarize the function, design principles, and penetrating mechanisms of arginine-rich CPPs, and outline their biomedical applications in drug delivery and biosensing in tumors.

Microneedles in Advanced Microfluidic Systems: A Systematic Review throughout Lab and Organ-on-a-Chip Applications

Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a stand-alone tool to be combined with microfluidic devices. For that purpose, lab- or organ-on-a-chip are being developed. This systematic review aims to summarize the most recent progress in these emerging systems, to identify their advantages and limitations, and discuss promising potential applications of MNs in microfluidics. Therefore, three databases were used to search papers of interest, and their selection was made following the guidelines for systematic reviews proposed by PRISMA. In the selected studies, the MNs type, fabrication strategy, materials, and function/application were evaluated. The literature reviewed showed that although the use of MNs for lab-on-a-chip has been more explored than for organ-on-a-chip, some recent studies have explored this applicability with great potential for the monitoring of organ models. Overall, it is shown that the presence of MNs in advanced microfluidic devices can simplify drug delivery and microinjection, as well as fluid extraction for biomarker detection by using integrated biosensors, which is a promising tool to precisely monitor, in real-time, different kinds of biomarkers in lab- and organ-on-a-chip platforms.

Chitin and Chitosan: Prospective Biomedical Applications in Drug Delivery, Cancer Treatment, and Wound Healing.

Chitin and its derivative chitosan are highly abundant polymers in nature, appearing in both the shells and exoskeletons of various marine and non-marine species. Since they possess favorable properties, such as biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, they have gained recent attention due to their enormous potential biomedical applications. The polycationic surface of chitosan enables it to form hydrogenic and ionic bonds with drug molecules, which is one of its most useful properties. Because chitosan is biocompatible, it can therefore be used in drug delivery systems. The development of chitosan-based nanoparticles has also contributed to the significance of chitin as a drug delivery system that can deliver drugs topically. Furthermore, chitin can be used in cancer treatment as a vehicle for delivering cancer drugs to a specific site and has an antiproliferative effect by reducing the viability of cells. Finally, chitosan can be used as a wound dressing in order to promote the faster regeneration of skin epithelial cells and collagen production by fibroblasts. As discussed in this review, chitin and chitosan have diverse applications in the medical field. Recognizing the biomedical applications of these two polymers is essential for future research in tissue engineering and nanobiotechnology.

Recent Advances in Inorganic Chiral Nanomaterials.

Inorganic nanoparticles offer a multifunctional platform for biomedical applications in drug delivery, biosensing, bioimaging, disease diagnosis, screening, and therapies. Homochirality prevalently exists in biological systems composed of asymmetric biochemical activities and processes, so biomedical applications essentially favor the usage of inorganic chiral nanomaterials, which have been widely studied in the past two decades. Here, the latest investigations are summarized including the characterization of 3D stereochirality, the bionic fabrication of hierarchical chirality, extension of the compositional space to poly-elements, studying optical activities with the (sub-)single-particle resolution, and the experimental demonstration in biomedical applications. These advanced studies pave the way toward fully understanding the two important chiral effects (i.e., the chiroptical and enantioselective effects), and prospectively promote the flexible design and fabrication of inorganic chiral nanoparticles with engineerable functionalities to solve diverse practical problems closely associated with environment and public health.

Self-healing hyaluronic acid hydrogels based on dynamic Schiff base linkages as biomaterials

Natural hydrogels are widely investigated for biomedical applications because of their structures similar to extracellular matrix of native tissues, possessing excellent biocompatibility and biodegradability. However, they are often susceptible to mechanical disruption. In this study, self-healing hyaluronic acid (HA) hydrogels are fabricated through a facile dynamic covalent Schiff base reaction. Dialdehyde-modified HA (AHA) precursor was synthesized, and then the AHA/cystamine dihydrochloride (AHA/Cys) hydrogels were formed by blending AHA and Cys at acidic pH levels. By varying Cys to AHA ratio, the hydrogel morphology, swelling and kinetics of gelation could be controlled. Gelation occurred fast, which was predominantly attributed to Schiff base reaction between the dialdehyde groups on AHA and amimo groups on Cys. The hydrogel exhibited improved mechanical properties with increase in Cys content. Furthermore, due to dynamic imine bonds, this hydrogel demonstrated excellent self-healing ability based on the stress after mechanical disruption. Also, it was found to be pH-responsive and injectable. Taken together, this kind of hyaluronic acid hydrogel can provide promising future for various biomedical applications in drug delivery, bioprinting, smart robots and tissue regeneration.

Leucine-coated cobalt ferrite nanoparticles: Synthesis, characterization and potential biomedical applications for drug delivery

This work was primarily focused on the synthesis, characterization and biomedical applications of cobalt ferrite (CoFe2O4) nanoparticles, which were synthesized by a facile solvothermal method using an amino acid of Leucine (Leu) as the surface coating agents. The morphology, structure and properties of the as-synthesized uncoated and Leu-coated CoFe2O4 nanoparticles were characterized in detail by means of XRD, SEM, TEM, DLS, FTIR, XPS, TGA and SQUID. More importantly, it was found that the Leu-coated CoFe2O4 nanoparticles can be used as the efficient drug delivery with a drug loading capacity of 0.32 mg/mg for doxorubicin hydrochloride (DOX), and the loaded DOX demonstrated a sustained and progressive release manner. The in vitro cytotoxicity studies towards the HeLa cells were carried out, and the results indicated that the Leu-coated CoFe2O4 nanoparticles exhibited a relatively high cell viability compared with that of bare CoFe2O4 nanoparticles and the DOX loaded Leu-coated CoFe2O4 nanoparticles presented an obvious cytotoxic effect on HeLa cells.

Self-assembled poly(2-ethyl-2-oxazoline)/malonic acid hollow fibers in aqueous solutions

Well-defined poly(2-ethyl-2-oxazoline) (PEOX)/Malonic Acid (MA) fibers having hollow tubular morphology were shown to form in aqueous solutions at 25 °C by complexation induced self-assembly between PEOX and MA. The fibers had diameter of ~1–3 μm and a wall thickness of ~40 nm. Different interactions between PEOX and MA were identified for complexation as a function of pH. At pH2, when both ends of MA were protonated, H-bonded complexation was the driving interaction in the fiber formation. IR data showed both PEOX -CO band and MA -COOH band in dried fibers formed at pH2. The downshift in the CO stretching of PEOX by as much as 15 cm−1 confirmed the H-bonded complexation. The interaction enthalpy of PEOX and MA was determined by isothermal titration calorimetry (ITC) as −49.39 kJ/mol which is consistent with H-bonding. Thermogravimetric analysis (TGA) of the fibers showed two distinct decomposition temperatures one between 100 and 150 °C corresponding to MA and the other one at 350–450 °C corresponding to PEOX which also indicated the presence of both components in the fibers. At pH4, when one end of MA was protonated and the other end was ionized, electrostatic complexation between carboxylate (–COO−) group of MA and the amide group of PEOX was the driving interaction in the fiber formation. At pH7, when both ends of MA were ionized, fiber formation was significantly hindered. The results are important in understanding the role of different interactions in the hollow fiber formation mechanism as a function of pH. pH-responsive hollow fibers have great potential to be used in biomedical applications for drug delivery and release purposes.

Smart Hydrogels with Antibacterial Properties Built from All Natural Building Blocks

Smart hydrogels with multistimuli responsiveness have been increasingly exploited as soft matters for biomedical applications in drug delivery, tissue engineering, and bioactuators. While many of t...

Adsoption of Cationic Dye on Anionic Hydrogel and Its Second Use for Drug Delivery with Antibacterial Properties

Poly(2,3-epoxypropylmethacrylate-co-2-acrylamido-2-methyl-1-propanesulfonic acid), p(EPMA-co-AMPS), hydrogels were prepared by free radical aqueous copolymerization reaction of 2,3-epoxypropylmethacrylate (EPMA) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) using N,N’methylenebisacrylamide (MBA) as a crosslinking agent and ammonium persulfate (APS) as a free radical initiator and investigated its adsorption capacity, drug carrier and antibacterial activity. P(EPMA-co-AMPS) hydrogels were characterized by swelling studies, FTIR, SEM, TPA and elemental analysis. Adsorption studies were conducted with a batch system for the removal of methylene blue (MB) from aqueous solutions and then, the results were analyzed both with isotherms and kinetic parameters. The maximum adsorption capacity of the hydrogel for MB was found to be 217.6 mg/g. The obtained data agreed with a pseudo-second-order rate expression and fit the Langmuir isotherm very well. Moreover, hydrogels were found to be very useful as a drug carrier in biomedical applications for drug delivery devices by using gentamicin sulfate (GS) as a model drug. Additionally, the hydrogel showed good antibacterial performance on both Gram‐positive bacteria (Bacillus cereus) and Gram‐negative bacteria (Salmonella typhimurium) as model bacterias.

Factors relating to the biodistribution & clearance of nanoparticles & their effects on in vivo application.

Nanoparticles have promising biomedical applications for drug delivery, tumor imaging and tumor treatment. Pharmacokinetics are important for the in vivo application of nanoparticles. Biodistribution and clearance are largely defined as the key points of pharmacokinetics to maximize therapeutic efficacy and to minimize side effects. Different engineered nanoparticles have different biodistribution and clearance processes. The interactions of organs with nanoparticles, which are determined by the characteristics of the organs and the biochemical/physical properties of the nanoparticles, are a major factor influencing biodistribution and clearance. In this review, the clearance functions of organs and the properties related to pharmacokinetics, including nanoparticle size, shape, biodegradation and surface modifications are discussed.

Silica Materials for Biomedical Applications in Drug Delivery, Bone Treatment or Regeneration, and MRI Contrast Agent

In recent years, the biomedical research using variety of silica materials has shown an outstanding growth. The silica-based materials are playing a major role to harnessing dual or multiple modalities in therapeutics and diagnostics. The unique and favourable physico-chemical characteristics of mesoporous silica nanoparticles are increasingly attracting the researchers to utilise them into various fields of biomedical research. Apart from the mesoporous silica nanoparticles, a range of other silica-based materials have also been applied quite extensively in the biomedical research. This article presents a brief overview of three particular areas of biomedical applications where a broad range of silica-based materials have been covered: (1) variety of drug delivery including intracellular drug delivery systems using silica-based carriers; (2) applications of silica materials as bone grafts or implants for bone disease treatment and bone regeneration; and (3) development of silica-based contrast agents for magnetic resonance image enhancement. Biocompatibility, bio-toxicity, tissue responses, cellular uptakes, and, how the effects of size, shape, morphology, structural and textural properties of the silica materials impact on their utilities are discussed. Perspectives, insights and critical reflections into a range of aspects are illustrated.

Protein Engineered Triblock Polymers Composed of Two SADs: Enhanced Mechanical Properties and Binding Abilities.

Recombinant methods have been used to engineer artificial protein triblock polymers composed of two different self-assembling domains (SADs) bearing one elastin (E) flanked by two cartilage oligomeric matrix protein coiled-coil (C) domains to generate CEC. To understand how the two C domains improve small molecule recognition and the mechanical integrity of CEC, we have constructed CL44AECL44A, which bears an impaired CL44A domain that is unstructured as a negative control. The CEC triblock polymer demonstrates increased small molecule binding and ideal elastic behavior for hydrogel formation. The negative control CL44AECL44A does not exhibit binding to small molecule and is inelastic at lower temperatures, affirming the favorable role of C domain and its helical conformation. While both CEC and CL44AECL44A assemble into micelles, CEC is more densely packed with C domains on the surface enabling the development of networks leading to hydrogel formation. Such protein engineered triblock copolymers capable of forming robust hydrogels hold tremendous promise for biomedical applications in drug delivery and tissue engineering.

Synthesis and Application of Aurophilic Poly(Cysteine) and Poly(Cysteine)-Containing Copolymers.

The redox capacity, as well as the aurophilicity of the terminal thiol side groups, in poly(Cysteine) lend a unique characteristic to this poly(amino acid) or polypeptide. There are two major application fields for this polymer: (i) biomedical applications in drug delivery and surface modification of biomedical devices and (ii) as coating for electrodes to enhance their electrochemical sensitivity. The intended application determines the synthetic route for p(Cysteine). Polymers to be used in biomedical applications are typically polymerized from the cysteine N-carboxyanhydride by a ring-opening polymerization, where the thiol group needs to be protected during the polymerization. Advances in this methodology have led to conditions under which the polymerization progresses as living polymerization, which allows for a strict control of the molecular architecture, molecular weight and polydispersity and the formation of block copolymers, which eventually could display polyphilic properties. Poly(Cysteine) used as electrode coating is typically polymerized onto the electrode by cyclic voltammetry, which actually produces a continuous, pinhole-free film on the electrode via the formation of covalent bonds between the amino group of Cysteine and the carbon of the electrode. This resulting coating is chemically very different from the well-defined poly(Cysteine) obtained by ring-opening polymerizations. Based on the structure of cysteine a significant degree of cross-linking within the coating deposited by cyclic voltammetry can be assumed. This manuscript provides a detailed discussion of the ring-opening polymerization of cysteine, a brief consideration of the role of glutathione, a key cysteine-containing tripeptide, and examples for the utilization of poly(Cysteine) and poly(Cysteine)-containing copolymers, in both, the biomedical as well as electrochemical realm.

Synthesis of Europium-Doped Fluorapatite Nanorods and Their Biomedical Applications in Drug Delivery.

Europium (Eu)-doped fluorapatite (FA) nanorods have a biocompatibility similar to that of hydroxyapatite (HA) for use as cell imaging biomaterials due to their luminescent property. Here, we discuss the new application of europium-doped fluorapatite (Eu-FA) nanorods as an anticancer drug carrier. The Eu-FA nanorods were prepared by using a hydrothermal method. The morphology, crystal structure, fluorescence, and composition were investigated. The specific crystal structure enables the effective loading of drug molecules. Doxorubicin (DOX), which was used as a model anticancer drug, effectively loaded onto the surface of the nanorods. The DOX release was pH-dependent and occurred more rapidly at pH 5.5 than at pH 7.4. The intracellular penetration of the DOX-loaded Eu-FA nanorods (Eu-FA/DOX) can be imaged in situ due to the self-fluorescence property. Treatment of melanoma A375 cells with Eu-FA/DOX elicited a more effective apoptosis rate than direct DOX treatment. Overall, Eu-FA exhibits potential for tracking and treating tumors and may be potentially useful as a multifunctional carrier system to effectively load and sustainably deliver drugs.

Near-Infrared Light-Responsive Semiconductor Polymer Composite Hydrogels: Spatial/Temporal-Controlled Release via a Photothermal "Sponge" Effect.

Near-infrared (NIR) light-responsive hydrogels are important for biomedical applications, such as remote-controlled release, but the NIR agents previously used were largely limited to heavy-metal inorganic materials such as gold nanoparticles. In this article, we report a new type of NIR photothermal-responsive hydrogel that can undergo structural changes in response to NIR light for biomedical applications in drug delivery and controlled release. The hydrogels synthesized by integrating a narrow-bandgap semiconductor polymer poly(diketopyrrolopyrrole-alt-3,4-ethylenedioxythiophene) with the polymerization of N-isopropylacrylamide show rapid and reversible mechanical shrinkage upon NIR light irradiation and can serve as carriers for anticancer drug loading and spatial/temporal control of drug release. These stimuli-responsive hydrogels, which can be prepared in different sizes and shapes, integrate photothermal properties and hydrogel characteristics and can provide on-demand, repeated, remote-controlled drug delivery for biomedical applications such as cancer treatment.

Agar/gelatin bilayer gel matrix fabricated by simple thermo-responsive sol-gel transition method

We present a simple and environmentally-friendly method to generate an agar/gelatin bilayer gel matrix for further biomedical applications. In this method, the thermally responsive sol-gel transitions of agar and gelatin combined with the different transition temperatures are exquisitely employed to fabricate the agar/gelatin bilayer gel matrix and achieve separate loading for various materials (e.g., drugs, fluorescent materials, and nanoparticles). Importantly, the resulting bilayer gel matrix provides two different biopolymer environments (a polysaccharide environment vs a protein environment) with a well-defined border, which allows the loaded materials in different layers to retain their original properties (e.g., magnetism and fluorescence) and reduce mutual interference. In addition, the loaded materials in the bilayer gel matrix exhibit an interesting release behavior under the control of thermal stimuli. Consequently, the resulting agar/gelatin bilayer gel matrix is a promising candidate for biomedical applications in drug delivery, controlled release, fluorescence labeling, and bio-imaging.

Preparation of green and gelatin-free nanocrystalline cellulose capsules

The ambiguous source and uncontrolled solubility of gelatin make it crucial to develop gelatin capsule substitutes. Nanocrystalline cellulose (NCC) of excellent mechanical performance, good biocompatibility and green origin has drawn many attentions as a new class of biomaterials. In this work, NCC capsule was prepared by dipping method with PEG and glycerol as plasticizer. The effect of PEG and glycerol on the rheological property of NCC gel and the surface morphology of NCC capsule was evaluated. The disintegration time of NCC capsule meet the criteria in United States Pharmacopoeia (USP32-701).There is no significant difference in the release of sulfuric acid between gelatin capsule and NCC capsule. NCC capsule thus has the potential as a green platform for biomedical applications in drug delivery.

Metal-organic-frameworks for biomedical applications in drug delivery, and as MRI contrast agents.

The metal-organic-frameworks (MOFs) materials are increasingly gaining attraction to utilise into biomedical applications. MOFs are playing a major role to harnessing dual or multiple modalities in therapeutics and diagnostics. MOFs are mostly devised for particular biomedical application by post-synthetic functionalization or modification using variety of polymers, bio-ligands, and silica coating processes. This article presents a brief overview of two particular areas of biomedical applications where a broad range of MOFs have been used: (1) variety of drug delivery including intracellular drug delivery systems using the MOFs-based carriers; and, (2) development of MOFs-based contrast agents for magnetic resonance image enhancement. Biocompatibility, bio-toxicity, tissue responses, cell viability, cellular uptakes, and, how the effects of size, shape, structural, and morphological properties of the MOFs impact on the utilities in drug delivery and as MRI contrast agents, are discussed. Perspectives, insights and critical reflections into a range of aspects, and future outlook are illustrated. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1184-1194, 2017.

The Effective Role of Hydroxyapatite Based Composites in Anticancer Drug Delivery Systems.

Tumors consist of a heterogeneous population of cancer cells carrying multiple genetic mutations. During the past few decades, efforts have focused on curing cancer using various methods. However, traditional cancer therapies still carry some drawbacks, such as limited application for only a few cancer types, killing of normal cells, poor specificity, and associated toxicity. To overcome these disadvantages, drug-delivery methods that emphasize biomaterials have been developed and applied to optimize cancer treatments. Hydroxyapatite (HAP) is a biocompatible inorganic material that can be applied in biomedical drug-delivery applications. This review discusses the features and properties of HAP that make it an effective biomaterial and provides a comprehensive summary of recent studies in which HAP and composites containing HAP were applied as anticancer drug carriers. We believe that HAP-based composites show great promise for cancer treatment using controlled release of therapeutic agents, leading to enhanced efficiency, selective release of drugs, and prohibition of cancer cell proliferation.