Controlled Drug Delivery Research Articles

Finite element method for natural convection flow of Casson hybrid (Al2O3–Cu/water) nanofluid inside H-shaped enclosure

The fundamental problem in electronic cooling systems is the implementation of a cavity such that it can be used to provide localized cooling to specific components, such as CPUs or GPUs, enhancing their performance and longevity. It can also be used in microfluidic devices for controlled drug delivery, where precise control of fluid flow is crucial. The present article numerically explores the free convection non-Newtonian Casson hybrid nanofluid phenomena that occur within an H-shaped cavity while heated from the middle. The heating efficiency and heat flow in a cavity are influenced by perpendicular hot walls that connect two vertical closed channels. A numerical solution is obtained by implementing the Galerkin finite element method to solve the partial differential equation. The numerical outcomes are depicted on the contour of streamlines and isotherms for different parameters in the following ranges: 0.1 ≤ η ≤ 0.4, 0.005≤ϕhp≤0.020, 0.1 ≤ γ ≤ 2, and 103 ≤ Ra ≤ 106 at fixed Pr = 6.2. In addition, line graphs show rate of heat transfer within the enclosure using the average Nusselt number for these parameters. Increased aspect ratios (η = 0.4) result in a minimal rate of heat transfer enhancement, whereas decreasing η leads to a significantly higher average Nusselt number and maximum heat transfer within the cavity. The convective rate of heat transfer increases with the presence of hybrid nanoparticles inside an H-shaped cavity for all Rayleigh numbers. The rotation of the Casson hybrid nanofluid also rises as the volume ratio of nanoparticles increases. For a fixed aspect ratio (A.R) of 0.1, the heat dissipation is 6.91% at a lower ϕhp value of 0.005 at a fixed Ra value of 105. However, it increases to 7.072% for a higher ϕhp value of 0.02 at Ra = 105. With increasing Ra number, ϕhp, and γ, the number NuAve increases.

Synthesis and rheological analyzes of temperature and light sensitive gels comprising amphiphilic azobenzene polymers, chitosan and pluronic F127

AbstractThis study investigates the reinforcement of pluronic (PF127) based temperature responsive hydrogels with photosensitive functionalities to create smart and injectable materials. For this purpose, 4‐[4‐[(4‐phenyl)azo]phenoxy] methacrylate (PAzPMA) was synthesized and further polymerized via reversible addition‐fragmentation chain transfer (RAFT) polymerization. The structures of the copolymers were characterized by several techniques such as Fourier‐transform infrared (FT‐IR), nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The azobenzene‐functionalized copolymer was combined with P127 solid polymer in micelle form and with P127 micelles in solid form to obtain PF127‐AzoMx and PF127‐AzoPx gels, respectively. When the temperature profiles of the PF127‐AzoMx and PF127‐AzoPx systems were compared with PF127, sol–gel phase transition were shifted to lower temperatures due to stronger hydrophobic interactions. Additionally, different concentrations of N,N,N‐trimethyl chitosan (f‐chitosan) were added to the gel systems and their rheological properties were investigated by exposing them to UV light. It has been observed that the presence and concentration of f‐chitosan are important for the variation of the interactions' strength between the micelles. The study highlights the potential of multifunctional hydrogels for specific biomedical applications that combine sensitivity to both thermal and optical stimuli for controlled drug delivery and tissue engineering purposes.

Synthesis of stimuli-responsive copolymeric hydrogels for temperature, reduction and pH-controlled drug delivery

Stimuli-responsive copolymeric hydrogels (CH) are synthesized for controlled drug delivery. Oxidized glycyrrhizic acid is connected to acrylamide through Schiff base reaction, which is then copolymerized with N,N-bis (acryloyl) cystamine and N-isopropylacrylamide by free-radical polymerization for the loading of 5-fluorouracil with a loading efficiency of 96.7 %. The lower critical solution temperature of the CH is 39.14 °C. The N-isopropylacrylamide unit in the CH is sensitive to temperature, endowing the CH with temperature sensitivity. The carboxyl groups of oxidized glycyrrhizic acid can be deprotonated in alkaline solutions, and the electrostatic repulsions between the resultant carboxylate can cause swelling of the CH. The disulfide bond (S–S) of the N,N-bis (acryloyl) cystamine unit can be reduced to sulfhydryl (–SH) by glutathione, and thus the CH is also reduction-sensitive. Therefore, temperature, reduction and pH-controlled delivery of 5-fluorouracil from the CH is achieved. Cytotoxicity assay reveals that the drug-free hydrogels have good biocompatibility while the CH shows high cytotoxicity against human hepatoma SMMC-7721 cells, and the cell viability is only 25 % at the CH concentration of 1 mg mL−1.

EVA implants for controlled drug delivery to the inner ear

This study evaluated the potential of poly(ethylene vinyl acetate) (EVA) copolymers as matrix formers in miniaturised implants, allowing to achieve controlled drug delivery into the inner ear. Due to the blood-cochlea barrier, it is impossible to reliably deliver a drug to this tiny and highly sensitive organ in clinical practice. To overcome this bottleneck, different EVA implants were prepared by hot melt extrusion, altering the vinyl acetate content and implant diameter. Dexamethasone was incorporated as a drug with anti-inflammatory and anti-fibrotic activity. Its release was measured into artificial perilymph, and the systems were thoroughly characterised before and after exposure to the medium by optical and scanning electron microscopy, SEM-EDX analysis, DSC, X-ray powder diffraction, X-ray microtomography and texture analysis. Notably, the resulting drug release rates were much higher than from silicone-based implants of similar size. Furthermore, varying the vinyl acetate content allowed for adjusting the desired release patterns effectively: With decreasing vinyl acetate content, the crystallinity of the copolymer increased, and the release rate decreased. Interestingly, the drug was homogeneously distributed as tiny crystals throughout the polymeric matrices. Upon contact with aqueous fluids, water penetrates the implants and dissolves the drug, which subsequently diffuses out of the device. Importantly, no noteworthy system swelling or shrinking was observed for up to 10 months upon exposure to the release medium, irrespective of the EVA grade. Also, the mechanical properties of the implants can be expected to allow for administration into the inner ear of a patient, being neither too flexible nor too rigid.

Enhancing therapeutic effects alginate microencapsulation of thyme and calendula oils using ionic gelation for controlled drug delivery

This study focuses on encapsulating and characterizing essential oils such as thyme and calendula oils, which are known for their therapeutic properties but are limited in pharmaceutical formulations due to their low water solubility and instability, with alginate microspheres. Alginate presents an excellent option for microencapsulation due to its biocompatibility and biological degradability. The ionic gelation (IG) technique, based on the ionic binding between alginate and divalent cations, allows the formation of hydrogel materials with high water content, mechanical strength, and biocompatibility. The microspheres were characterized using FT-IR, SEM, and swelling analyses. After determining the encapsulation efficiency and drug loading capacity, the microspheres were subjected to dissolution studies under simulated digestion conditions. It was observed that the swelling percentage of the microspheres in simulated gastric fluid (SGF) ranged from ∼15% to 100%, while in simulated intestinal fluid (SIF) it ranged from ∼150% to 325%. Thyme oil, with low viscosity, exhibited higher encapsulation efficiency than marigold oil. The highest encapsulation efficiency was observed in A-TO-2 microspheres, while the highest drug loading capacity was observed in A-TO-5 microspheres. During the examination of the dissolution profiles of the microspheres, dissolution rates ranging from 10.98% to 23.56% in SGF and from 52.44% to 63.20% in SIF were observed.

Enhanced effects of slowly co-released TGF-β3 and BMP-2 from biomimetic calcium phosphate-coated silk fibroin scaffolds in the repair of osteochondral defects

Bioactive agents have demonstrated regenerative potential for cell-free bone tissue engineering. Nevertheless, certain challenges persist, including ineffective delivery methods and confined therapeutic potency. Here, we demonstrated that the biomimetic calcium phosphate coating system (BioCaP) could effectively uptake and slowly release the incorporated bioactive agents compared to the surface absorption system via osteoclast-mediated degradation of BioCaP coatings. The release kinetics were determined as a function of time. The release rate was stable without remarkable burst release during the first 1 day, followed by a sustained release from day 7 to day 19. Then, we developed the bi-functional BioCaP-coated silk fibroin scaffolds enabling the effective co-delivery of TGF-β3 and BMP-2 (SFI-T/SFI-B) and the corresponding slow release of TGF-β3 and BMP-2 exhibited superior potential in promoting chondrogenesis and osteogenesis without impairing cell vitality in vitro. The SFI-T/SFI-B scaffolds could improve cartilage and bone regeneration in 5 × 4 mm rabbit osteochondral (OC) defect. These findings indicate that the biomimetic calcium-phosphate coated silk fibroin scaffolds with slowly co-released TGF-β3 and BMP-2 effectively promote the repair of OC defects, hence facilitating the future clinical translation of controlled drug delivery in tissue engineering.Graphic

Development and Applications of PLGA Hydrogels for Sustained Delivery of Therapeutic Agents.

Poly(lactic-co-glycolic acid) (PLGA) hydrogels are highly utilized in biomedical research due to their biocompatibility, biodegradability, and other versatile properties. This review comprehensively explores their synthesis, properties, sustained release mechanisms, and applications in drug delivery. The introduction underscores the significance of PLGA hydrogels in addressing challenges like short half-lives and systemic toxicity in conventional drug formulations. Synthesis methods, including emulsion solvent evaporation, solvent casting, electrospinning, thermal gelation, and photopolymerization, are described in detail and their role in tailoring hydrogel properties for specific applications is highlighted. Sustained release mechanisms-such as diffusion-controlled, degradation-controlled, swelling-controlled, and combined systems-are analyzed alongside key kinetic models (zero-order, first-order, Higuchi, and Peppas models) for designing controlled drug delivery systems. Applications of PLGA hydrogels in drug delivery are discussed, highlighting their effectiveness in localized and sustained chemotherapy for cancer, as well as in the delivery of antibiotics and antimicrobials to combat infections. Challenges and future prospects in PLGA hydrogel research are discussed, with a focus on improving drug loading efficiency, improving release control mechanisms, and promoting clinical translation. In summary, PLGA hydrogels provide a promising platform for the sustained delivery of therapeutic agents and meet diverse biomedical requirements. Future advancements in materials science and biomedical engineering are anticipated to further optimize their efficacy and applicability in clinical settings. This review consolidates the current understanding and outlines future research directions for PLGA hydrogels, emphasizing their potential to revolutionize therapeutic delivery and improve patient outcomes.

Multifunctional Biocomposites: Synthesis, Characterization, and Prospects for Regenerative Medicine and Controlled Drug Delivery.

This article presents a new method for preparing multifunctional composite biomaterials with applications in advanced biomedical fields. The biomaterials consist of dicalcium phosphate (DCPD) and bioactive silicate glasses (SiO2/Na2O and SiO2/K2O), containing the antibiotic streptomycin sulfate. Materials were deeply characterized by X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy, and zeta potential analysis, UV-visible spectrophotometry, and ion-exchange measurement were applied in a simulating body fluid (SBF) solution. The main results include an in situ chemical transformation of dicalcium phosphate into an apatitic phase under the influence of silicate solutions and the incorporation of the antibiotic. The zeta potential showed a decrease in surface charge from ζ = -24.6 mV to ζ = -16.5 mV. In addition, a controlled and prolonged release of antibiotics was observed over a period of 37 days, with a released concentration of up to 755 ppm. Toxicity tests in mice demonstrated good tolerance of the biomaterials, with no significant adverse effects. Moreover, these biomaterials have shown potent antibacterial activity against various bacterial strains, including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, suggesting their potential use in tissue engineering, drug delivery, and orthopedic and dental implants. By integrating the antibiotic into the biomaterial composites, we achieved controlled release and prolonged antibacterial efficacy. This research contributes to advancing biomaterials by exploring innovative synthetic routes and showcasing their promise in regenerative medicine and controlled drug delivery.

Biodegradable Controlled Drug Delivery Platform Based on Carboxylated Mesoporous Silica Nanoparticles––Zinc Oxide Quantum Dots

Biodegradable Controlled Drug Delivery Platform Based on Carboxylated Mesoporous Silica Nanoparticles––Zinc Oxide Quantum Dots

Evaluation of the Effects of Locally Applied Resveratrol and Cigarette Smoking on Bone Healing

Background: Bone healing is a complex process controlled by various mechanisms. It is known that cigarette smoking (CS) negatively affects bone healing by disrupting many of these mechanisms. In an effort to find ways to eliminate these negative effects caused by CS, studies have been conducted on various vitamins, antioxidants, and medications. Since high doses and repeated injections are required to increase the therapeutic effect of conventional drug applications, controlled drug delivery systems have been developed to avoid such problems. This study aimed to investigate the effects of resveratrol (RES), which has been made into a controlled drug delivery system, on bone healing in rats that were experimentally exposed to cigarette smoke to create a chronic smoking model. Methods: After establishing a chronic CS model by exposing the subjects to cigarette smoke of six cigarettes/day for four weeks, monocortical critical size defects of 3 mm (SD ± 0.02 mm) in diameter were created in the femur using a trephine bur. During the operation, the defects in RES groups were filled locally with a gel-formed solution of RES (50 µM) and Pluronic F-127 (14 µL). CS exposure was continued during the bone healing period after surgery. All groups were sacrificed one month after the operation, and femur samples were taken. Results: The obtained samples were examined by histomorphometric and immunohistochemical techniques; osteoblast count, new bone area, macroscopic filling score, vascularization, and proliferation were evaluated. Conclusion: The results of this study indicate that CS negatively affects bone healing and that local application of RES reduces this effect.

Gold Nanocluster: A Photoelectric Converter for X-Ray-Activated Chemotherapy.

Despite the promise of activatable chemotherapy, the development of a spatiotemporally controllable strategy for prodrug activation in deep tissues remains challenging. Herein, a proof-of-concept is proposed for a gold nanocluster-based strategy that utilizes X-ray irradiation to trigger the liberation of platinum (Pt)-based prodrug conjugates, thus enabling radiotherapy-directed chemotherapy. Mechanistically, the irradiated activation of prodrugs is achieved through direct photoelectron transfer from the excited-state gold nanoclusters to the Pt(IV) center, resulting in the release of cytotoxic Pt(II) agents. Compared to the traditional combination of chemotherapy and radiotherapy, this radiotherapy-directed chemotherapy strategy offers superior antitumor efficacy and safety benefits through spatiotemporal synergy at the tumor site. Additionally, this strategy elicits robust immunogenic cell death and yields profound outcomes for combined immunotherapy of breast cancer. This versatile strategy is ushering in a new era of radiation-mediated chemistry for controlled drug delivery and the precise regulation of biological processes.

Synthesis and characterization of ZnO quantum dot-functionalized mesoporous nanocarriers for controlled drug delivery

In this study, ZnO quantum dots (ZnO@QDs) were synthesized and functionalized with 2nd generation poly amido amine (2GPD) using 3-amino-propyl tri-methoxy silane as the initiator core, facilitated by tetramethylammonium hydroxide (TMAH) to enhance stability against oleate coating. Concurrently, a mesoporous substrate with a unique morphology was developed as a drug reservoir for doxorubicin loading. ZnO quantum dots displayed photoluminescence radiation, with dimensions ranging from 5 to 7 nm and exhibiting spherical morphology. The cubic structure of the synthesized mesoporous nanocatalysts was also confirmed. Brunauer-Emmett-Teller analysis indicated a multidimensional porous structure of the nanocarriers, while zeta potential analysis showed a stable system (approximately −9.6 mV). Fourier transform infrared spectroscopy, X-ray diffraction, and energy dispersive spectroscopy corroborated these findings. Drug release studies demonstrated sustained release under acidic conditions (pH 5.5), with an efficiency of approximately 94 %. These results highlight the potential applications of this nanosystem for controlled drug delivery, underscoring its practical implications in the field of nanotechnology.

Unravelling the role of tumor microenvironment responsive nanobiomaterials in spatiotemporal controlled drug delivery for lung cancer therapy.

Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli-physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)-that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals.

Protective Encapsulation of a Bioactive Compound in Starch-Polyethylene Glycol-Modified Microparticles: Degradation Analysis with Enzymes.

Starch is a promising polymer for creating novel microparticulate systems with superior biocompatibility and controlled drug delivery capabilities. In this study, we synthesized polyethylene glycol (PEG)-modified starch microparticles and encapsulated folic acid using a solvent-mediated acid-base precipitation method with magnetic stirring, which is a simple and effective method. To evaluate particle degradation, we simulated physiological conditions by employing an enzymatic degradation approach. Our results with FTIR and SEM confirmed the successful synthesis of starch-PEG microparticles encapsulating folic acid. The average size of starch microparticles encapsulating folic acid was 4.97 μm and increased to 6.01 μm upon modification with PEG. The microparticles were first exposed to amylase at pH 6.7 and pepsin at pH 1.5 at different incubation times at physiological temperature with shaking. Post-degradation analysis revealed changes in particle size and morphology, indicating effective enzymatic degradation. FTIR spectroscopy was used to assess the chemical composition before and after degradation. The initial FTIR spectra displayed characteristic peaks of starch, PEG, and folic acid, which showed decreased intensities after enzymatic degradation, suggesting alterations in chemical composition. These findings demonstrate the ongoing development of starch-PEG microparticles for controlled drug delivery and other biomedical applications and provide the basis for further exploration of PEG-starch as a versatile biomaterial for encapsulating bioactive compounds.

Lignin‐based polyurethane composites enhanced with hydroxyapatite for controlled drug delivery and potential cellular scaffold applications

Lignin‐based polyurethane composites enhanced with hydroxyapatite for controlled drug delivery and potential cellular scaffold applications

PH and temperature dual-responsive magnetic yolk-shell mesoporous silica nanoparticles for controlled drug delivery

New magnetic yolk-shell mesoporous silica nanoparticles (Fe3O4@V-mSiO2-PNVCL) were prepared by grafting temperature-sensitive amino-terminated poly (N-vinylcaprolactam) (PNVCL-NH2) on the surface of aldehyde-functionalized magnetic mesoporous silica nanoparticles (Fe3O4@V-mSiO2-CHO) through a Schiff base reaction. Various characterizations were used to confirm the structures, and the drug loading and release behaviors were studied. The drug loading was achieved as PNVCL stretched at room temperature and the drug loading content was up to 54.7% due to the large cavities. The encapsulation of drug from leakage in the blood environment was realized as PNVCL collapsed at physiological temperature. The fracture of pH-liable imine bonds in a slightly acidic tumor environment triggered the burst release of cargo. The Fe3O4@V-mSiO2-PNVCL showed super paramagnetic behavior (21.01 emu∙g−1) which could achieve magnetic targeting. The MTT assay confirmed that the nanoparticles exhibited low cytotoxicity. Furthermore, the cellular uptake experiments indicated that DOX-loaded nanoparticles were successfully internalized into cancer cells. Therefore, the composite nanoparticles are ideal choices for drug carriers.

A lignocellulose nanofibril-poly(vinyl alcohol) hydrogel with controlled drug delivery for wound healing

Employing lignocellulosic nanofibers (LCNF) with natural, high specific mechanical performance and abundant functional groups to design a hydrogel as a drug-sustained release carrier, which conforms to the concept of green and sustainable development. Herein, we facilely extracted carboxylated lignocellulose nanofibrils (CLCNF) from bagasse via a deep eutectic solvent (DES) and mechanical defibrillation-based strategy. The CLCNF was crosslinked with poly(vinyl alcohol) (PVA) to obtain a nanocomposite hydrogel (PVA/CLCNF/B) whereupon the mechanical strength and drug release behavior were improved in the process. Consequently, the lignocellulose nanocomposite hydrogel presented a high compression modulus (3.92 MPa) and significant sustained-release effect with a release rate of 80.73 % after 336 h. The delivery behavior of the PVA/CLCNF/B composite hydrogel could be controlled by acidic pH conditions. The TH release kinetics of PVA/CLCNF/B hydrogel in different phosphate buffer saline (PBS) followed the Korsmeyer-Peppas model better, and the release of TH occurred through the Fickian diffusion mechanism. Importantly, in vivo experiments and histopathological studies showed that TH-loaded PVA/CLCNF/B hydrogel had a superior pro-healing rate. Overall, the incorporation of CLCNF into a hydrogel may have considerable potential as a drug delivery carrier for drug release and therapy. SynopsisAdding the CLCNF from bagasse into PVA dispersions obtained a hydrogel for pH-responsive drug delivery can accelerate wound healing.

A Review on Microspheres as a Promising Drug Carrier

The targeted drug delivery is designed for endeavouring to concentrate the drug in the tissues of curiosity while reducing relative concentration of medication in the remaining tissues. There for drug is localized on the targeted site. Hence, surrounding tissues are not affected by the drug. Controlled drug delivery systems can overcome the issues associated with conventional medication therapy and improve a drug's therapeutic efficacy. Microspheres are free-flowing powders made of proteins or synthetic polymers with particle sizes ranging from 1 to 1000 µm. The multiplicity of techniques for preparing microspheres provides numerous chances to manage elements of drug administration and improve the therapeutic efficacy of a certain medicine. There are several techniques for delivering a medicinal chemical to the target region in a prolonged controlled release manner. Microspheres contain a drug encased in a unique polymeric membrane, making them ideal for novel drug delivery strategies such as diseased cell sorting, diagnostics, gene and genetic materials, safe and effective in vivo delivery, and supplements as miniature versions of diseased organs and tissues. Keywords: Microspheres, Controlled release Therapeutic effectiveness, novel medication delivery.

Bohemian Rhapsody of Future Drug Delivery Systems: Rational Changes Necessary for the Next Revolution.

Controlled drug delivery technology has matured for more than 70 years, starting from a twice-a-day oral formulation to 6 month long-acting injectable formulations. Further technological advances require superior formulations to treat various diseases more efficiently. Developing future formulations with practical innovations for treating existing and new diseases necessitates our continued efforts to overcome at least three main hurdles. They include (i) drug delivery with reduced side effects, (ii) long-term treatment of chronic diseases, and (iii) the overcoming of biological barriers. Such efforts start with the improved ability to accurately test drug delivery efficacy using proper controls. Future development can be aided by artificial intelligence if used properly. The next revolution of drug delivery systems will be augmented if implementation is given equal weight as discovery. Such a process can be accelerated with the systemic revamp of the research funding structure and cultivating a new generation of scientists who can think differently.

Fluconazole adsorption and release study using KIT-6 for targeted and controlled drug delivery system

ABSTRACT This study presents the development of a mesoporous silica, i.e. KIT-6 synthesised using the hydrothermal technique, followed by the loading of fluconazole as the model drug using the post-impregnation method. The results of drug entrapment studies exposed that 76% of the drug was entrapped in the silica matrix. The drug release rate was investigated in phosphate buffer with pH = 6.8. The fluconazole-loaded KIT-6 prolonged the drug’s release for 12 hours, ensuring Higuchi’s square root kinetics, with diffusion via the matrix as the releasing mechanism, which revealed that the release rate was under control. The MTT assay-based biocompatibility experiments on Vero cells show that the pure and drug-loaded composite systems have minimal cytotoxicity. Hence, drug delivery and adsorption may be facilitated, and repeated administration of drugs is reduced by a controlled drug release rate using the prepared silicious composite.