Controlled Drug Release System Research Articles

Engineering of surface modified Ti3C2Tx MXene based dually controlled drug release system for synergistic multitherapies of cancer

Easily surface-modified MXenes have been extensively investigated as nanoplatforms for drug delivery because of their high drug-loading capacity, multiple drug release modes, and good biocompatibility. Herein, we report the synthesis of an MXene@Au-PEG drug delivery platform for the high loading of the chemotherapeutic doxorubicin (DOX), which has both near infrared (NIR) laser-triggered and pH-responsive drug release modes. Owing to surface modification with thiol polyethylene glycol aldehyde chains (SH-PEG-CHO) connected to the MXene by Au nanoparticles (Au NPs), the MXene@Au-PEG-DOX system shows good photothermal stability, biosafety, and histocompatibility during in vivo and vitro tests. Additionally, based on the good photothermal conversion capability of both Au particles and MXene, the system exhibits synergistic photothermal ablation and chemotherapy for tumor treatment. The passively targeted release properties of the MXene@Au-PEG drug delivery platform also enhance the cellular uptake of DOX at tumor sites, thereby improving the efficiency of the drug. Thus, the reported preparation strategy for a surface-modified MXene-based drug delivery platform with high drug-loading capacity, multiple drug release modes, and synergistic therapy, provides a promising demonstration of the potential application of MXene-based nanomaterials for cancer treatment.

Preparation and evaluation of niosomal chitosan-based in situ gel formulation for direct nose-to-brain methotrexate delivery

Achieving effective treatments for various brain disorders due to the blood-brain barrier existence and the brain's complex structure has become a challenging goal. To overcome these challenges, one of the non-invasive strategies aimed at direct brain drug delivery is the use of the intranasal route. Novel drug delivery systems can be used to overcome the limitations in this administration route. This study suggested niosomal methotrexate (MTX) in situ gel formulation, which could be a suitable candidate for drug delivery to the brain. Here, niosomal MTX was prepared by a modified reverse-phase evaporation method, optimized with the aid of the design expert® software, and characterized. Optimum niosomal MTX with particle size, zeta potential, and entrapment efficiency (EE%), equal to 130.5 nm, −38.5 mV, and 91.39 %, respectively, were added into the temperature-sensitive in situ gel formulation composed of chitosan and Poloxamer 407. This study demonstrates that the simultaneous use of niosome and in situ gel formulations causes long-term persistence in the nasal cavity and helps us to have a more controlled drug release system with higher brain concentration, lower plasma concentration, higher Kp, and lower side effects compared to the free drug (MTX solution), MTX-gel (MTX-loaded in situ gel), and niosomal MTX formulations.

LP-SBA-15/Ketorolac Nanocomposite: Development, Characterization, and Mathematical Modeling of Controlled Keto Release

Drug-controlled release systems can keep the level of drugs in precise doses in the body above the optimal level and with low toxicity. We propose the nanomaterial LP-SBA-15 as an attractive new host for drug delivery systems due to its high biocompatibility, in vivo biodegradability, and low toxicity. LP-SBA-15/Ketorolac was prepared and characterized by XRD, FTIR, UV-Vis DRS, TEM, and texture analysis, determining the adsorption capacity and its release and achieving the required therapeutic efficacy. The host shows the ordered mesoporous nanochannels with a diameter of 11-12 nm, maintaining the structure with the incorporation of Keto. The mechanism of drug release from the LP-SBA-15 host was evaluated. Different mathematical models were used to adjust the experimental data, the Ritger-Peppas model followed by the Weibull model the best ones. The promising results we obtained for the release of the drug thoroughly using the new material, reaching a rapid initial release rate, and maintaining a constant rate afterward, allow us to maintain the concentration of the drug in the therapeutic efficacy range, applying it largely to the treatment of diseases that require a rapid response.

Powering ≈50 µm Motion by a Molecular Event in DNA Crystals.

A major challenge in material design is to couple nanoscale molecular and supramolecular events into desired chemical, physical, and mechanical properties at the macroscopic scale. Here, a novel self-assembled DNA crystal actuator is reported, which has reversible, directional expansion and contraction for over 50 μm in response to versatile stimuli, including temperature, ionic strength, pH, and redox potential. The macroscopic actuation is powered by cooperative dissociation or cohesion of thousands of DNA sticky ends at the designed crystal contacts. The increase in crystal porosity and cavity in the expanded state dramatically enhances the crystal capability to accommodate/encapsulate nanoparticles/proteins, while the contraction enables a "sponge squeezing" motion for releasing nanoparticles. This crystal actuator is envisioned to be useful for a wide range of applications, including powering self-propelled robotics, sensing subtle environmental changes, constructing functional hybrid materials, and working in drug controlled-release systems.

Effect of electrochemical oxidation and drug loading on the antibacterial properties and cell biocompatibility of titanium substrates

A combination of {text{ TiO}}_{2} nanotube array (TON) and controlled drug release system is employed to provide enhanced surface properties of titanium implants. Electrochemical anodization process is used to generate TON for introducing, vancomycin, an effective antibacterial drug against Staphylococcusaureus. TON loaded vancomycin is then coated with a number of layers of 10% gelatin using spin coating technique. The gelatin film is reinforced with graphene oxide (GO) nanoparticles to improve the surface bioactivity. The surface of the samples is characterized by field emission electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), and contact angle measurement. The results illustrate that the TON was constructed and vancomycin molecules are successfully loaded. The drug release study shows that the amount of released vancomycin is controlled by the thickness of gelatin layers. With an increase in gelatin film layers from 3 to 7, the release of vancomycin in the burst release phase decreased from 58 to 31%, and sustained release extended from 10 to 17 days. The addition of GO nanoparticles seems to reduce drug release in from 31 to 22% (burst release phase) and prolonged drug release (from 17 to 19 days). MTT assay indicates that samples show no cytotoxicity, and combination of GO nanoparticles with gelatin coating could highly promote MG63 cell proliferation. Soaking the samples in SBF solution after 3 and 7 days demonstrates that hydroxy apatite crystals were deposited on the TON surface with GO-gelatin coating more than surface of TON with gelatin. Moreover, based on the results of disc diffusion assay, both samples (loaded with Vancomycin and coated with gelatin and gelatin-GO) with the inhibition zones equaled to 20 mm show effective antibacterial properties against S. aureus. The evidence demonstrates that titania nanotube loaded with vancomycin and coated with gelatin-GO has a great potential for general applicability to the orthopedic implant field.

Adenosine triphosphate/pH dual-responsive controlled drug release system with high cancer/normal cell selectivity and low side toxicity.

Most drug-delivery systems (DDS) suffer from poor selectivity to cancer/normal cells or the complicated synthetic process. Herein, we employed a novel facile method to develop an oligodeoxy nucleotides based DDS composed with adenosine-5'- triphosphate (ATP) aptamer and a pH responsive cytosine (C) DNA fragment for specific daunomycine (DNM) delivery. The DDS has ATP/pH dual-responsive drug release, can selectively internalize into tumor cell lines and thus has ultrahigh cancer/normal cell selectivity over the individual drug. The non-chemical synthesis, controllable dual-responsive intracellular drug release, and high cancer/normal cell selectivity endowed the DDS high biocompatibility and significant tumor suppression.

Quercetin-Crosslinked Chitosan Films for Controlled Release of Antimicrobial Drugs.

Natural polymer-based films, due to their favorable biological and mechanical properties, have demonstrated great potential as coatings for biomedical applications. Among them, chitosan films have been widely studied both as coating materials and as controlled drug release systems. Crosslinkers are often used to tune chitosan’s crosslinking degree and thus to control the drug release kinetics. For this purpose, quercetin, a plant-derived natural polyphenol, has gained attention as a crosslinker, mainly for its intrinsic anti-inflammatory, antioxidant, and antibacterial features. In this study, chitosan films crosslinked with three different concentrations of quercetin (10, 20, and 30% w/w) have been used as controlled release systems for the delivery of the antibacterial drug trimethoprim (TMP, 10% w/w). Physicochemical and antimicrobial properties were investigated. Surface wettability and composition of the films were assessed by contact angle measurements, X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR), respectively. The release kinetic of TMP in phosphate-buffered saline (PBS) and 2-(N-morpholino) ethanesulfonic acid (MES) was studied over time. Finally, antibacterial properties were assessed on E. coli and S. aureus through Kirby–Bauer disc diffusion and micro-dilution broth assays. Results show that quercetin, at the tested concentrations, clearly increases the crosslinking degree in a dose-dependent manner, thus influencing the release kinetic of the loaded TMP while maintaining its bactericidal effects. In conclusion, this work demonstrates that quercetin-crosslinked chitosan films represent a promising strategy for the design of antibiotic-releasing coatings for biomedical applications.

Synthesis of antibiotic-modified silica nanoparticles and their use as a controlled drug release system with antibacterial properties

In this study, monodispersed silica nanoparticles were synthesized using the Stöber method. The synthesized nanoparticles underwent a range of surface modifications and were converted to nanoparticles with drug release and antibacterial features. For modification, firstly –NH2 groups were created on the silica nanoparticle surface using (3-Aminopropyl)triethoxysilane (APTES). In the second stage, hexachlorocyclotriphosphazene (Phz) molecules were bound to the silica nanoparticle surfaces due to these amino groups. In the final stage of modification, the chloride groups in the hexachlorocyclotriphosphazene structure were modified with trimethoprim (TMP) and nanoparticles with antibacterial properties were obtained. The modified silica nanoparticles were characterized with scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), and Thermogravimetric analysis (TGA). The silica-based nanoparticles were used for release of rhodamine 6G, chosen as a model drug. As a result of the drug release studies, the modified silica nanoparticles were found to abide by the Korsmeyer–Peppas low power model and non-Fickian release mechanism as release model. Additionally, nanoparticles both loaded and not loaded with the model drug were determined to have antibacterial properties against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus bacteria.

Progress of hollow materials in diagnosis of COVID-19

Since the outbreak of COVID-19 in Wuhan, China, it has dramatically changed the global geopolitics, economics, and even society standard norms. The present world scenario is changed regarding business, traveling, and education. Rapid global dissemination and the high mortality rate of coronaviruses are the greatest challenges for drug developers. It will be moving forward toward the identification and treatment of emerging coronaviruses with the aid of nanotechnology. The COVID-19 pandemic raised the question of researchers’ capability to manage this dilemma in a short period. In the present review, we described how hallow material could be developed as a pro-drug that shows an excellent therapeutic effect. Hollow nanoparticles that exploration of antiviral or diagnostic agents against emerging coronaviruses. Hollow nanomaterials in vaccine development are essential because hollow nanocomposites are suitable for mimicking viral structures and antigen delivery. A biosensor that generates a signal from a transducer for comparing and analyzing biological conjugates such as cell receptors, antibodies, RNA, DNA, and nucleic acids. Different biosensors, such as graphene-based biosensors, nanoplasmonic sensor chips, nanomaterial biosensors, electrochemical biosensors, dual modality biosensors, and optical biosensors, have several advantages, characteristics, and a wide range of applications, most remarkably in medical treatment and are used for monitoring and diagnosis. This review focuses on modern experimental studies to identify intelligent and innovative bio/nanomaterials and matrices for developing targeted and controlled drug release systems, nanosensors and nanovaccines to combat pathogenic viruses.

Activated Carbon Fiber Cloth/Biomimetic Apatite: A Dual Drug Delivery System

A biomaterial that is both bioactive and capable of controlled drug release is highly attractive for bone regeneration. In previous works, we demonstrated the possibility of combining activated carbon fiber cloth (ACC) and biomimetic apatite (such as calcium-deficient hydroxyapatite (CDA)) to develop an efficient material for bone regeneration. The aim to use the adsorption properties of an activated carbon/biomimetic apatite composite to synthetize a biomaterial to be used as a controlled drug release system after implantation. The adsorption and desorption of tetracycline and aspirin were first investigated in the ACC and CDA components and then on ACC/CDA composite. The results showed that drug adsorption and release are dependent on the adsorbent material and the drug polarity/hydrophilicity, leading to two distinct modes of drug adsorption and release. Consequently, a double adsorption approach was successfully performed, leading to a multifunctional and innovative ACC-aspirin/CDA-tetracycline implantable biomaterial. In a second step, in vitro tests emphasized a better affinity of the drug (tetracycline or aspirin)-loaded ACC/CDA materials towards human primary osteoblast viability and proliferation. Then, in vivo experiments on a large cortical bone defect in rats was carried out to test biocompatibility and bone regeneration ability. Data clearly highlighted a significant acceleration of bone reconstruction in the presence of the ACC/CDA patch. The ability of the aspirin-loaded ACC/CDA material to release the drug in situ for improving bone healing was also underlined, as a proof of concept. This work highlights the possibility of bone patches with controlled (multi)drug release features being used for bone tissue repair.

Niosomes: A Promising Novel Nano Carrier for Drug Delivery

Niosomes are vesicles, which are formulated by hydrating the mixture of cholesterol, non-ionic surfactant and other biodegradable lipids. Niosomes increase the drug activity as compare to their conventional dosage form of a drug. Niosomes can be used as carrier of amphiphilic and lipophilic drugs. Niosomes may overcome the issues related to instability, fast degradation, low bioavailability, and insolubility of medications. The structure of niosomes either multilamellar or unilamellar, is depends on the method of formulation. Niosomes contain very efficient drug delivery potential for site-specific delivery of anti-cancer, anti-infective agents, etc. Niosomes are stable as well as cost effective carriers as compared with other drug formulations. Niosomes also have various applications in parental drug delivery system, topical drug delivery system, oral drug delivery system and novel drug delivery system such as targeted drug delivery system and controlled drug release system.

Review of Recent Advances and Their Improvement in the Effectiveness of Hydrogel-Based Targeted Drug Delivery: A Hope for Treating Cancer.

Using hydrogels for delivering cancer therapeutics is advantageous in pharmaceutical usage as they have an edge over traditional delivery, which is tainted due to the risk of toxicity that it imbues. Hydrogel usage leads to the development of a more controlled drug release system owing to its amenability for structural metamorphosis, its higher porosity to seat the drug molecules, and its ability to shield the drug from denaturation. The thing that makes its utility even more enhanced is that they make themselves more recognizable to the body tissues and hence can stay inside the body for a longer time, enhancing the efficiency of the delivery, which otherwise is negatively affected since the drug is identified by the human immunity as a foreign substance, and thus, an attack of the immunity begins on the drug injected. A variety of hydrogels such as thermosensitive, pH-sensitive, and magnetism-responsive hydrogels have been included and their potential usage in drug delivery has been discussed in this review that aims to present recent studies on hydrogels that respond to alterations under a variety of circumstances in "reducing" situations that mimic the microenvironment of cancerous cells.

Personalized and Programmable Microneedle Dressing for Promoting Wound Healing.

Microneedle (MN) dressings, with the ability of transdermal drug delivery, have played an essential role in the field of wound healing. However, patients may still feel uncomfortable when sensitive unhealing wounds are pieced by strong needles. Here, inspired by the structure of mosquito mouthparts, which possess a fixation part and a liquid-transferring part, we present a novel MN wound dressing with superfine needle tips, personalized pattern design, programmable needle length, and multiple mechanical strengths for intelligent and painless drug delivery. By simply stretching the silicone rubber (Ecoflex) molds before engraving, superfine MNs can be formed in the restored molds. Meanwhile, by utilizing intelligent image recognition, precise treatment for irregular wounds is achieved. Notably, combined with temperature-responsive N-isopropylacrylamide (NIPAM) hydrogel and inverse opal (IO) photonic crystals (PCs), a controllable drug release system has been achieved on MN dressings. Moreover, the performance of the MN dressing in facilitating wound recovery has been demonstrated by full-thickness skin wounds of a mouse model. These results indicate that novel personalized and programmable MN wound dressings are of considerable value in the field of wound management.

From Blood to Regenerative Tissue: How Autologous Platelet-Rich Fibrin Can Be Combined with Other Materials to Ensure Controlled Drug and Growth Factor Release.

The purpose of this review is to examine the latest literature on the use of autologous platelet-rich fibrin as a drug and growth factor carrier system in maxillofacial surgery. Autologous platelet-rich fibrin (PRF) is a unique system that combines properties such as biocompatibility and biodegradability, in addition to containing growth factors and peptides that provide tissue regeneration. This opens up new horizons for the use of all beneficial ingredients in the blood sample for biomedical purposes. By itself, PRF has an unstable effect on osteogenesis: therefore, advanced approaches, including the combination of PRF with materials or drugs, are of great interest in clinics. The main advantage of drug delivery systems is that by controlling drug release, high drug concentrations locally and fewer side effects within other tissue can be achieved. This is especially important in tissues with limited blood supply, such as bone tissue compared to soft tissue. The ability of PRF to degrade naturally is considered an advantage for its use as a “warehouse” of controlled drug release systems. We are focusing on this concentrate, as it is easy to use in manipulations and can be delivered directly to the surgical site. The target audience for this review are researchers and medical doctors who are involved in the development and research of PRFs further studies. Likewise, surgeons who use PRF in their work to treat patients and who advice patients to take the medicine orally.

Synthesis and characterization of temperature-sensitive microspheres based on acrylamide grafted hydroxypropyl cellulose and chitosan for the controlled release of amoxicillin trihydrate

This study deals with the preparation of temperature-sensitive chitosan/hydroxypropyl cellulose-graft-polyacrylamide (CS/HPC-g-PAAm) blend microspheres as a controlled drug release system. For this purpose, HPC-g-PAAm copolymers of hydroxypropyl cellulose (HPC) with acrylamide (AAm) were synthesized using cerium (IV) ammonium nitrate as initiator. The HPC-g-PAAm copolymers were characterized by using Fourier transform infrared spectroscopy (FTIR), elemental analysis, and differential scanning calorimetry (DSC). Lower critical solution temperatures (LCST) of the synthesized copolymers were determined. Temperature-sensitive blend microspheres of HPC-g-PAAm and chitosan were prepared by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker in the hydrochloric acid catalyst (HCl) and they were used to achieve controlled release of amoxicillin trihydrate (AMX), an antibiotic drug. The microspheres were characterized by DSC, X-ray diffraction (X-RD), and FTIR spectroscopy. In addition, surfaces of empty and drug-loaded microspheres were examined by scanning electron microscopy (SEM). The effects of variables such as CS/HPC-g-PAAm ratio, drug/polymer ratio, amount of cross-linker, and reaction time of grafting on AMX release were investigated at three different pH environments (1.2, 6.8, 7.4) at 25 °C, 37 °C, and 50 °C. The release results showed that the microspheres had temperature sensitivity and the AMX release was slightly more controlled by especially increasing graft yield (%).

Bionanocomposite Beads Based on Montmorillonite and Biopolymers as Potential Systems for Oral Release of Ciprofloxacin

AbstractThe number of studies of controlled drug-release systems is growing constantly. Bionanocomposite materials which can be prepared from the combination of biopolymers with inorganic solids such as clay minerals offer interesting alternatives for use as drug-delivery systems. In the present study, new bionanocomposite drug-release systems were prepared from the intercalation of the antibiotic drug ciprofloxacin into montmorillonite using an ion-exchange reaction. In order to prepare more stable systems for oral ciprofloxacin release, this ciprofloxacin-clay intercalation compound was incorporated into i-carrageenan-gelatin biopolymer blend to produce bionanocomposite materials. Bionanocomposites of two distinct i-carrageenan and gelatin mass ratios were conformed as beads through an ionic gelification reaction with Ca2+ ions, and dried by freeze-drying where liquid nitrogen or conventional freezing was adopted in the freezing step. The resulting ciprofloxacin-clay hybrid was characterized by X-ray diffraction (XRD) analysis, Fourier-transform infrared (FTIR) spectroscopy, solid state 13C Nuclear Magnetic Resonance (NMR), thermal analysis, and scanning electron microscopy (SEM). The montmorillonite-ciprofloxacin hybrid incorporated into the bionanocomposite beads was evaluated by in vitro release studies which showed a significant difference in the release profiles in the aqueous medium used to simulate the gastrointestinal tract, depending on the blend composition and the freezing method employed in the preparation of the beads. The results point to bionanocomposite systems based on ciprofloxacin-clay hybrids and biopolymers that may be used as devices in the biomedical area.

Shark Tooth-Inspired Microneedle Dressing for Intelligent Wound Management.

Intelligent management beyond therapeutic drug treating holds significant prospects in facilitating the recovery of intractable chronic wounds. Here, inspired by the flat and inclined structure of shark teeth, we present a shark tooth-inspired microneedle patch for intelligent wound management. By simply replicating negative molds fabricated by laser engraving and using origami, such a biomimetic microneedle patch can be fabricated easily and rapidly. The biomimetic structures endow the microneedle patch with stable adhesion during the long-term recovery process of chronic wounds. Porous ordered structures and a temperature-responsive hydrogel are utilized to construct a controllable drug release system on the microneedle patch. The microfluidic channel composed of microneedle arrays and porous ordered structures enables a microneedle patch with the capacity to analyze several inflammatory factors. In addition, MXene electronics was patterned on the microneedle patch in order to achieve sensitive motion monitoring. Also, it was demonstrated from invivo diabetic rat experiments that recovery of full-thickness cutaneous wounds including stripe-shaped and circular wounds can be facilitated by employing the drug-loaded biomimetic microneedle patch.

Nanogels as controlled drug release systems for Coenzyme Q10 and Resveratrol for cosmetic application

Nanogels as controlled drug release systems for Coenzyme Q10 and Resveratrol for cosmetic application

Controlled release of anticancer drugs via the magnetic magnesium iron nanoparticles modified by graphene oxide and polyvinyl alcohol: Paclitaxel and docetaxel

Objective(s)Paclitaxel (PTX) and docetaxel (DTX) belong to the family of taxanes drugs which have been employed for treatment of ovarian, breast, lung, head, neck, gastric, pancreatic, bladder, prostate and cervical cancer. Controlled drug release systems improve the effectiveness of drug therapy by modifying the release profile, biodistribution, stability and solubility, bioavailability of drugs and minimize the side effects of anticancer drugs. So, the purpose of the present study was to synthesize the modified nanocomposite for the controlled releases of these drugs.Materials and MethodsMagnetic magnesium iron oxide nanoparticles were synthesized via the co-precipitation chemical method and then composited with graphene oxide and modified by polyvinyl alcohol. The physicochemical characterization of the prepared nanocomposites was investigated by scanning electron microscope (SEM), X-ray powder diffraction (XRD) , Fourier-transform infrared spectroscopy and vibrating-sample magnetometer.ResultsSpecific characteristics such as adsorption capacity, monodispersity, stability and hydrophilicity of magnetic nanomaterials were studied in the controlled release of anticancer drugs. Drug loading content and drug loading efficiency and release rate of drugs were investigated in vitro at different pH with ultraviolet-visible spectroscopy (UV-Vis). DLE and DLC of PTX and DTX in the modified magnetic nanocomposites were calculated as 85.2 ± 2.7% and 7.74 ± 0.24% , 89.4 ± 1.2% and 8.12 ± 0.11% of, respectively. The cumulative release amount of PTX and DTX from magnetic modified nanocomposites at pHs 5.8, 7.4 over 100 h were 58 % and 40 % and 54 % and 37 %, respectively.ConclusionThe potential of modified nanocomposite in drug delivery systems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of modified nanocomposite generated by different surface coatings. The generally sustained and controlled release profile of DTX (or PTX) facilitates the application of modified nanocomposite for the delivery of anticancer drugs.

Recent Developments in Lactone Monomers and Polymer Synthesis and Application.

Lactones are a group of compounds that have been known for several decades. The commercial importance of lactones results from the possibility of manufacturing of a broad scope of derivatives and polymers with a wide spectrum of applications. In this work the synthesis and characterization of simple lactones are described, which due to the easy methods of the synthesis are of high importance for the industry. The chemical as well as biochemical methods are included with special attention paid to the methods that avoid metal catalysts, initiators or toxic solvents, allowing the use of the final products for the medical applications, e.g., for controlled drug-release systems, resorbable surgical threads, implants, tissue scaffolds or for the production of drugs. Lactone-based derivatives, such as polymers, copolymers, composites or three-dimensional structures are also presented. The work is focused on the methods for the synthesis of lactones and lactones derivates, as well as on the special properties and application of the studied compounds.