Release Of Dexamethasone Research Articles

Self-Healing Thermosensitive Hydrogel for Sustained Release of Dexamethasone for Ocular Therapy.

The aim of this study was to develop an injectable hydrogel delivery system for sustained ocular delivery of dexamethasone. To this end, a self-healing hydrogel consisting of a thermosensitive ABA triblock copolymer was designed. The drug was covalently linked to the polymer by copolymerization of methacrylated dexamethasone with N-isopropylacrylamide (NIPAM) and N-acryloxysuccinimide (NAS) through reversible addition-fragmentation chain transfer (RAFT) polymerization, using poly(ethylene glycol) (PEG) functionalized at both ends with a chain transfer agent (CTA). Hydrogel formation was achieved by mixing aqueous solutions of the formed thermosensitive polymer (with a cloud point of 23 °C) with cystamine at 37 °C, to result in covalent cross-linking due to the reaction of the N-hydroxysuccimide (NHS) functionality of the polymer and the primary amines of cystamine. Rheological analysis showed both thermogelation and covalent cross-linking at 37 °C, as well as the self-healing properties of the formed network, which was attributed to the presence of disulfide bonds in the cystamine cross-links, making the system injectable. The release of dexamethasone from the hydrogel occurred through ester hydrolysis following first-order kinetics in an aqueous medium at pH 7.4 over 430 days at 37 °C. Based on simulations, administration of 100 mg of hydrogel would be sufficient for maintaining therapeutic levels of dexamethasone in the vitreous for at least 500 days. Importantly, dexamethasone was released from the hydrogel in its native form as determined by LC-MS analysis. Cytocompatibility studies showed that at clinically relevant concentrations, both the polymer and the cross-linker were well tolerated by adult retinal pigment epithelium (ARPE-19) cells. Moreover, the hydrogel did not show any toxicity to ARPE-19 cells. The injectability of the hydrogel, together with the long-lasting release of dexamethasone and good cytocompatibility with a retinal cell line, makes this delivery system an attractive candidate for treatment of ocular inflammatory diseases.

A predictive mechanistic model of drug release from surface eroding polymeric nanoparticles.

Effective drug delivery requires ample dosing at the target tissue while minimizing negative side effects. Drug delivery vehicles such as polymeric nanoparticles (NPs) are often employed to accomplish this challenge. In this work, drug release of numerous drugs from surface eroding polymeric NPs was evaluated in vitro in physiologically relevant pH5 and neutral buffers. NPs were loaded with paclitaxel, rapamycin, resiquimod, or doxorubicin and made from an FDA approved polyanhydride or from acetalated dextran (Ace-DEX), which has tunable degradation rates based on cyclic acetal coverage (CAC). By varying encapsulate, pH condition, and polymer, a range of distinct drug release profiles were achieved. To model the obtained drug release curves, a mechanistic mathematical model was constructed based on drug diffusion and polymer degradation. The resulting diffusion-erosion model accurately described drug release from the variety of surface eroding NPs. For drug release from varied CAC Ace-DEX NPs, the goodness of fit of the developed diffusion-erosion model was compared to several conventional drug release models. The diffusion-erosion model maintained optimal fit compared to conventional models across a range of conditions. Machine learning was then employed to estimate effective diffusion coefficients for the diffusion-erosion model, resulting in accurate prediction of in vitro release of dexamethasone and 3'3'-cyclic guanosine monophosphate-adenosine monophosphate from Ace-DEX NPs. This predictive modeling has potential to aid in the design of future Ace-DEX formulations where optimized drug release kinetics can lead to a desired therapeutic effect.

Development of fiber optic in vitro release testing method for dexamethasone release from the oil solutions.

For many parenteral drugs, there is still no standardized method for in vitro release (IVR) testing available. This article presents the development of a new IVR method for oil solutions using a dialysis membrane and USP II apparatus coupled to a fiber optic UV-Vis spectrometer. Experiments were performed using dexamethasone formulations containing castor oil as a solvent with the addition of cosolvents, 20 % (v/v) of isopropanol or Capryol® 90. Based on solubility testing results, castor oil was chosen as the best solvent amongst other vegetable oils, while a significant increase in solubility was obtained by adding either of the two cosolvents. Partitioning experiments were performed to ensure these formulations could achieve prolonged drug release. IVR testing was performed with model formulations and critical test parameters were varied in order to examine the method's sensitivity. The developed method was sensitive to temperature and stirring rate, while coupling the USP II apparatus with a fiber optic UV-Vis spectrometer enabled complete automation. Moreover, due to the interference of excipients on fiber optic detection of dexamethasone during the release testing, derivative spectroscopy was successfully introduced for the elimination of the interference. The developed IVR method described herein could be useful in preformulation investigations and the early development of novel formulations.

Phase separation control of PDMS/PNIPAAm IPNs and the effect on drug release

Poly (dimethyl siloxane) (PDMS) possesses good mechanical properties, oxygen permeability and optical transparency, making it an excellent candidate biomaterial, including for ophthalmic purposes. PDMS, however, is a hydrophobic polymer with poor water uptake and surface wettability, limiting its overall usefulness. Therefore, combination with one or more hydrophilic polymers, in which the immiscible materials form a stable interpenetrating polymer network (IPN), has the potential to improve the utility of PDMS in biomaterials applications. In the current work, IPNs consisting of PDMS and poly(N-isopropylacrylamide) (PNIPAAm) were synthesized. Three separate approaches were employed to generate IPNs possessing controllable and tunable phase separation, interfacial properties, and drug release kinetics. First, IPNs were synthesized with long chain PDMS prepolymers (LC-IPN), to create a looser host network capable of supporting the integration of a more interconnected PNIPAAm guest phase. In the second approach, NIPAAm was copolymerized with Tris(trimethylsiloxy) silyl-propyl methacrylate (TRIS) to compatibilize the silicone and hydrogel interface. Finally, a methacrylate-containing silicone-coupling agent, methacryloxypropyltriethoxysilane (MATO), was used to generate a PDMS host network that was more compatible with the guest PNIPAAm phase. LC-IPNs yielded materials with more pronounced temperature-induced phase transition properties compared with IPNs previously prepared. TRIS copolymerization and MATO crosslinking generated IPNs with decreased domain sizes and increased transparency. Release of the model drugs dexamethasone, timolol maleate, riboflavin and lysozyme were examined from the various IPNs. The results demonstrated that controlled release properties were possible, depending on the nature of the drug. Therefore, by varying the host and guest compositions to balance drug solubility and diffusion characteristics, it is possible to tune IPN release properties to meet the demands of the desired application. • IPNs consisting of PDMS and PNIPAAm were made 3 different ways. • Controllable and tunable phase separation, interfacial properties, and drug release. • Varying the compositions balances drug solubility and diffusion characteristics.

Safety and audiological outcome in a case series of tertiary therapy of sudden hearing loss with a biodegradable drug delivery implant for controlled release of dexamethasone to the inner ear.

BackgroundIntratympanic injections of glucocorticoids have become increasingly common in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL). However, due to their fast elimination, sustained applications have been suggested for local drug delivery to the inner ear.Materials and methodsThe study is based on a retrospective chart review of patients treated for ISSHL at a single tertiary (university) referral center. We included patients who were treated with a solid, biodegradable, poly(D,L-lactic-co-glycolic acid) (PLGA)-based drug delivery system providing sustained delivery of dexamethasone extracochlear into the round window niche (n = 15) or intracochlear into scala tympani (n = 2) for tertiary therapy of ISSHL in patients without serviceable hearing after primary systemic and secondary intratympanic glucocorticoid therapy. We evaluated the feasibility and safety through clinical evaluation, histological examination, and functional tests [pure-tone threshold (PTA), word recognition scores (WRS)].ResultsWith adequate surgical preparation of the round window niche, implantation was feasible in all patients. Histologic examination of the material in the round window niche showed signs of resorption without relevant inflammation or foreign body reaction to the implant. In patients where the basal part of scala tympani was assessable during later cochlear implantation, no pathological findings were found. In the patients with extracochlear application, average preoperative PTA was 84.7 dB HL (SD: 20.0) and 76.7 dB HL (SD: 16.7) at follow-up (p = 0.08). The preoperative average maximum WRS was 14.6% (SD: 17.9) and 39.3% (SD: 30.7) at follow-up (p = 0.11). Six patients (40%), however, reached serviceable hearing. The two patients with intracochlear application did not improve.ConclusionThe extracochlear application of the controlled release system in the round window niche and – based on limited observations - intracochlear implantation into scala tympani appears feasible and safe. Due to the uncontrolled study design, conclusions about the efficacy of the treatment are limited. These observations, however, may encourage the initiation of prospective controlled studies using biodegradable controlled release implants as drug delivery systems for the treatment of inner ear diseases.

Nanoarchitectonics of Cartilage-Targeting Hydrogel Microspheres with Reactive Oxygen Species Responsiveness for the Repair of Osteoarthritis

Clinically, intra-articular administration can hardly achieve the truly targeted therapy, and the drugs are usually insufficient to show local and long-term therapeutic effects because of their rapid clearance. Herein, inspired by the phenomenon that bees track the scent of flowers to collect nectar, we developed cartilage-targeting hydrogel microspheres with reactive oxygen species (ROS)-responsive ability via combining the microfluidic method and photopolymerization processes to integrate cartilage-targeting peptides and ROS-responsive nanoparticles in the hydrogel matrix. The hydrogel microspheres with cartilage-targeting properties promoted better retention in the joint cavity and enhanced cellular uptake of the nanoparticles. Moreover, the ROS-responsive nanoparticles could react with osteoarthritis (OA)-induced intracellular ROS, resulting in the depolymerization of nanoparticles, which could not only eliminate excess ROS and reduce inflammation but also promote the release of dexamethasone (Dex) and kartogenin (KGN) in situ, realizing effective OA therapy. It was demonstrated that this hydrogel microsphere showed favorable ROS-responsive ability and enhanced chondrogenic differentiation as well as the downregulation of pro-inflammatory factors in vitro. Additionally, the hydrogel microspheres, similar to bees, could target and effectively repair cartilage in the OA model. Thus, the injectable hydrogel microspheres exerted an excellent potential to repair OA and may also provide an effective avenue for inflammatory bowel disease therapy.

Influence of crosslinking on the drug release of PLLA/gelatin nonwovens

Abstract Electrospun fibers based on synthetic and natural polymers represent a promising approach in order to mimic the mechanical stability and the required cell-polymer interaction of the natural extracellular matrix (ECM), . In this biomedical context, the biodegradable medical grade poly-llactide (PLLA) and the natural gelatin are already well established. However, to obtain a stabilized structured PLLA/gelatin blend, crosslinking of gelatin is required. In this study, the influence of the post processed crosslinking via Glutaraldehyde (GTA) vapor and GTA solution on the morphological and physicochemical properties of the blend, as well as on the in vitrorelease of previously incorporated dexamethasone (DMS), was investigated. The addition of gelatin decreased the fiber diameter and increased the surface hydrophilicity, which is furthermore unaffected by the crosslinking process. The in vitrorelease of DMS was decisively changed by both, the addition of gelatin and the subsequent crosslinking processes. For all modified samples, a very rapid burst release of DMS was detected within the first 24 h, which is crucial for biomedical applications such as tumor therapy.

Coaxially Fabricated Dual‐Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration (Adv. Healthcare Mater. 16/2022)

Controlled Drug Release In article 2200571, Min Zhu, Xudong Wang, Kaili Lin and co-workers fabricate a novel dual-drug loading coaxially electrospinning fibrous mat with programmed release behavior. The early and rapid release of angiogenesis-promoting drug deferoxamine promotes the angiogenesis of vascular endothelial cells and the sustained release of osteogenesis-inducing drug dexamethasone enhances osteogenesis of bone mesenchymal stem cells, and synergistically boosts vascularized bone regeneration.

Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone.

Dexamethasone is one of the most often used corticosteroid drugs for sensorineural hearing loss treatment, and is used either by intratympanic injection or through systemic delivery. In this study, a biopolymer lipid hybrid microcarrier was investigated for enhanced local drug delivery and sustained release at the round window membrane level of the middle ear for the treatment of sensorineural hearing loss (SNHL). Dexamethasone-loaded and dexamethasone-free microparticles were prepared using biopolymers (polysaccharide and protein, pectin and bovine serum albumin, respectively) combined with lipid components (phosphatidylcholine and Dimethyldioctadecylammonium bromide) in order to obtain a biopolymer–liposome hybrid system, with a complex structure combining to enhance performance in terms of physical and chemical stability. The structure of the microparticles was evaluated by FTIR, XRD, thermal analysis, optical microscopy, and scanning electron microscopy (SEM). The encapsulation efficiency determination and the in vitro Dexamethasone release study were performed using UV-Vis spectroscopy. The high value of encapsulation efficiency and the results of the release study indicated six days of sustained release, encouraging us to evaluate the in vitro cytotoxicity of Dexamethasone-loaded microparticles and their influence on the cytotoxicity induced by Cisplatin on auditory HEI-OC1 cells. The results show that the new particles are able to protect the inner ear sensory cells.

ZnO-incorporated polyvinylidene fluoride/poly(ε-caprolactone) nanocomposite scaffold with controlled release of dexamethasone for bone tissue engineering

ZnO-incorporated polyvinylidene fluoride/poly(ε-caprolactone) nanocomposite scaffold with controlled release of dexamethasone for bone tissue engineering

Coaxially Fabricated Dual-Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration.

In clinical treatment, the bone regeneration of critical-size defects is desiderated to be solved, and the regeneration of large bone segment defects depends on early vascularization. Therefore, overcoming insufficient vascularization in artificial bone grafts may be a promising strategy for critical-size bone regeneration. Herein, a novel dual-drug programmed releasing electrospinning fibrous mat (EFM) with a deferoxamine (DFO)-loaded shell layer and a dexamethasone (DEX)-loaded core layer is fabricated using coaxial electrospinning technology, considering the temporal sequence of vascularization and bone repair. DFO acts as an angiogenesis promoter and DEX is used as an osteogenesis inducer. The results demonstrate that the early and rapid release of DFO promotes angiogenesis in human umbilical vascular endothelial cells and the sustained release of DEX enhances the osteogenic differentiation of rat bone mesenchymal stem cells. DFO and DEX exert synergetic effects on osteogenic differentiation via the Wnt/β-catenin signaling pathway, and the dual-drug programmed releasing EFM acquired perfect vascularized bone regeneration ability in a rat calvarial defect model. Overall, the study suggests a low-cost strategy to enhance vascularized bone regeneration by adjusting the behavior of angiogenesis and osteogenesis in time dimension.

Controlled release of low-molecular weight, polymer-free corticosteroid coatings suppresses fibrotic encapsulation of implanted medical devices

Inflammation-driven foreign body reactions, and the frequently associated encapsulation by fibrogenic fibroblasts, reduce the functionality and longevity of implanted medical devices and materials. Anti-inflammatory drugs, such as dexamethasone, can suppress the foreign body reaction for a few days post-surgery, but lasting drug delivery strategies for long-term implanted materials remain an unmet need. We here establish a thin-coating strategy with novel low molecular weight corticosteroid dimers to suppress foreign body reactions and fibrotic encapsulation of subcutaneous silicone implants. The dimer coatings are >75% dexamethasone by mass and directly processable into conformal coatings using conventional solvent-based techniques, such as casting or spray coating without added polymers or binding agents. In vitro, surface erosion of the coating, and subsequent hydrolysis, provide controlled release of free dexamethasone. In a rat subcutaneous implantation model, the resulting slow and sustained release profile of dexamethasone is effective at reducing the number and activation of pro-fibrotic macrophages both acutely and at chronic time points. Consequently, fibroblast activation, collagen deposition and fibrotic encapsulation are suppressed at least 45 days post-implantation. Thus, our approach to protect implants from host rejection is advantageous over polymeric drug delivery systems, which typically have low drug loading capacity (<30%), initial burst release profiles, and unpredictable release kinetics.

Modeling the Effects of Disease, Drug Properties, and Material on Drug Transport From Intraocular Lenses.

PurposeSurgically implanted intraocular lenses (IOLs) may be used as drug-delivery devices, but their effectiveness is not well defined. Computational fluid dynamics models were developed to investigate the capability of IOLs to release drugs at therapeutic concentrations.MethodsModels were generated using COMSOL Multiphysics. Primary open-angle glaucoma (POAG) and wet age-related macular degeneration (AMD) were simulated by reducing aqueous vein and choroidal blood flow, respectively. Release of dexamethasone, ganciclovir, or dextran was studied using common IOL materials, polydimethylsiloxane (PDMS) and poly(2-hydroxyethyl methacrylate) (PHEMA).ResultsDrug clearance proceeds mainly through choroidal blood flow. When fully constricted, maximum concentration at the choroid (Cmax) values increased by 32.4% to 39,800%. Compared to dexamethasone, Cmax in different tissues decreased by 6.07% to 96.0% for ganciclovir and dextran, and clearance rates decreased by 16% to 69% for ganciclovir and by 92% to 100% for dextran. Using PDMS as the IOL reduced clearance rates by 91.3% to 94.6% compared to PHEMA.ConclusionsIn diseased eyes, drugs accumulate mainly in posterior tissue; thus, choroidal drug toxicity must be assessed prior to IOL implantation in POAG and AMD patients. Moreover, drug properties modulated concentration profiles in all ocular segments. The hydrophobic small-molecule dexamethasone attained the highest concentrations and cleared the fastest, whereas hydrophilic macromolecular dextran attained the lowest concentrations and cleared the slowest. Furthermore, high concentrations were achieved quickly following release from PHEMA, whereas PDMS allowed for sustained release.Translational RelevanceIn silico results can guide scientists and clinicians regarding important physiological and chemical factors that modulate tissue drug concentrations from drug-eluting IOLs.

Dexamethasone-Loaded Ureasil Hydrophobic Membrane for Bone Guided Regeneration

Physical barrier membranes have been used to release active substances to treat critical bone defects; however, hydrophilic membranes do not present a prolonged release capacity. In this sense, hydrophobic membranes have been tested. Thus, this study aimed to develop hydrophobic membranes based on mixtures of ureasil–polyether-type materials containing incorporated dexamethasone (DMA) for the application in guided bone regeneration. The physicochemical characterization and biological assays were carried out using small-angle X-ray scattering (SAXS), an in vitro DMA release study, atomic force microscopy (AFM), a hemolysis test, and in vivo bone formation. The swelling degree, SAXS, and release results revealed that the u-PPO400/2000 membrane in the proportion of 70:30 showed swelling (4.69% ± 0.22) similar to the proportions 90:10 and 80:20, and lower than the proportion 60:40 (6.38% ± 0.49); however, an equal release percentage after 134 h was observed between the proportions 70:30 and 60:40. All u-PPO materials presented hemocompatibility (hemolysis ≤2.8%). AFM results showed that the treatments with or without DMA did not present significant differences, revealing a flat/smooth surface, with no pores and/or crystalline precipitates. Finally, in vivo results revealed that for both the commercial hydrophilic membrane and u-PPO400/2000 (70:30) after 60 days, the bone formation volume was 21%. In conclusion, hybrid membranes present unique characteristics for treating critical bone defects, considering the delayed and prolonged release results associated with the physical barrier capacity.

Dexamethasone microspheres and celecoxib microcrystals loaded into injectable gels for enhanced knee osteoarthritis therapy

The combination of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) has been commonly used for inflammation and chronic articular pain in the clinic. Nonetheless, the long-term administration of both medications might result in osteonecrosis of the knee due to repeated injections of steroids and side effects in the gastrointestinal and cardiovascular systems. To overcome these unmet medical needs, we designed a microsphere-microcrystal-gel delivery system for intra-articular injection. Dexamethasone (DEX)-loaded microspheres (DMs) were optimized by Plackett-Burman and Taguchi orthogonal designs to extend their retention time in the knee joint. Celecoxib (CLX) microcrystals (CMs) were manufactured using an ultrasonic method to improve solubility and bioavailability. Moreover, a green solvent-free method was employed to crosslink and synthesize a novel poloxamer 407/Gantrez® S97-based gel system (GZF), which can undergo the sol-gel transition at lower concentrations. Then, DM and CM were loaded by GZF to form intra-articular injectable gels (DM/CM/Gel). The in vitro release of DEX and CLX showed a fast phase in 24 h followed by a controlled release of ∼8 d. Both blank microspheres and GZF gels displayed great biocompatibility against RAW264.7 macrophages. The most suitable dosages of 5 nM DEX and 125 nM CLX in the formulation were chosen because of their significant effects against macrophage inflammation with a lower administrative amount. An In vivo animal evaluation showed that DM/CM/Gel suppressed the release of inflammatory cytokines (TNF-α and IL-6) after 21 d of treatment. In addition, a histological evaluation revealed that DM/CM/Gel interrupted the progression of cartilage surface denudation and matrix loss. Therefore, DM/CM/Gel provides a prospective strategy for reforming traditional therapy for chronic articular disease.

Engineered PD-1/TIGIT dual-activating cell-membrane nanoparticles with dexamethasone act synergistically to shape the effector T cell/Treg balance and alleviate systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease that is characterized by alterations in the balance between effector and regulatory CD4+ T cells. We observed the upregulation of the immune checkpoints (ICs) PD-1 and TIGIT in pathogenic CD4+ T cells during disease progression, and downregulation of their ligands PD-L1 and CD155. Inspired by biomimetic nanotechnology, we fabricated dexamethasone (DXM)-loaded IFN-γ-treated MHC class I deficient cancer membrane-coated nanoparticles (IM-MNPs/DXM) to safely harness the immunosuppressive power of tumor cells for the treatment of SLE. The IM-MNPs inherited the membrane functions, which allowed these particles to evade immune clearance and accumulate in inflammatory organs. The IM-MNPs specifically targeted SLE CD4+ T cells and agonist PD-1/TIGIT signaling to inhibit effector T cell function while enhancing the immunosuppressive function of regulatory T cells (Tregs). The sustained release of DXM inhibited the production of proinflammatory cytokines in the inflammatory microenvironment to further promote Treg-mediated immune homeostasis. The IM-MNPs/DXM showed significant therapeutic efficacy in ameliorating lupus nephritis (LN) and decreasing side effects in vivo. Therefore, the particle represents a promising platform to improve current SLE treatment efficacy while minimizing systemic side effects of DXM and ICs agonist therapy.

Evaluation and Optimization of Prolonged Release Mucoadhesive Tablets of Dexamethasone for Wound Healing: In Vitro-In Vivo Profiling in Healthy Volunteers.

The aim of the projected study was to design and develop a novel strategy for evaluating the mucoadhesive potential of polymeric tablets of dexamethasone (DXM) for local delivery against wounds. Therefore, formulations (Q1–Q7) were synthesized via direct compression method by varying the concentrations of polymers, i.e., ethyl cellulose (EC) and agar extract (AG). Moreover, the mucoadhesive polymeric tablets were characterized via physicochemical, in vitro, ex vivo and in vivo experiments. However, physicochemical characteristics such as FTIR showed no interaction with different polymeric combination. Surface pH of all formulations was normal to slightly alkaline. Highest hydration of up to 6.22% and swelling index was comprehended with maximum concentration of AG (50% of total tablet weight). Whereas, ex vivo and in vivo residence time and mucoadhesion were attributed to the increased concentrations of polymers. Moreover, Q7, (optimized formulation), containing 10% of EC and 40% of AG, exhibited maximum release of DXM (100%) over 8 h, along with sufficient mucoadhesive strength up to 11.73 g, following first-order kinetics having r2 value of 0.9778. Hemostatic effects and epithelialization for triggering and promoting wound healing were highly pronounced in cases of Q7. Furthermore, in vivo residence time was 7.84 h followed by salivary drug concentration (4.2 µg/mL). However, mucoadhesive buccal tablets showed stability for 6 months, thus following the standardization (ICH-Iva) stability zone. In summary, DXM mucoadhesive tablets seem to be an ideal candidate for eradication of wound infections via local targeted delivery.

Mesoporous Silk-Bioactive Glass Nanocomposites as Drug Eluting Multifunctional Conformal Coatings for Improving Osseointegration and Bactericidal Properties of Metal Implants.

Endowing metal implants with multifunctional traits to prevent implant-associated infections and improve osseointegration has become a pivotal facet in orthopedics and dental fixation. Herein, we report the synthesis of mesoporous 70S bioactive glass-silk fibroin nanocomposites inspired by the biomimetic organo-apatites of mineralized collagen. The mesoporous, biomimetic nanocomposites enabled loading of antibiotics (gentamicin and doxycycline) and favored their release in a rapid manner while preserving their bioactivity. Ease in modification of the mesoporous nanocomposites enabled tailoring of 3-(aminopropyl)-triethoxysilane to the silanol network of bioactive glass, which improved the loading capacity of the hydrophobic drug (dexamethasone). The modification favored the slow and sustained release of dexamethasone from the modified mesoporous nanocomposites, which is desired for mediating osteogenesis and immunomodulation. Conformal coatings of these drug-loaded nanocomposites were materialized on stainless-steel implants through a facile electrophoretic deposition (EPD) technique, wherein the deposition yield can be controlled by applied parameters. Antibiotic coatings exhibited antibacterial efficacy with bioactivity retained up to 28 days, while dexamethasone-loaded coatings favored mesenchymal stem cell adhesion and osteoinduction. The immunomodulatory roles were also ascertained, wherein M2 macrophage biasness was favored in dexamethasone-loaded coatings. The versatility of these mesoporous biomimetic nanocomposites guarantee the loading of scenario-specific drugs to aid their local delivery through the conformal EPD coatings developed over metal implants toward improving implant patency.

Transdermal Reservoir-Type Patch Loaded with a Pluronic F-127 Gel with Dexamethasone: Design, Development, and Characterization

The purpose of the present study was the development and characterization of a reservoir-type transdermal patch loaded with dexamethasone gel through physicochemical and biopharmaceutical tests to generate an innovative pharmaceutical form. The reservoir-type transdermal patch consists of three parts: i) the adhesive film, ii) an impermeable film with a reservoir function, and iii) dexamethasone formulated in a PF-127 gel. The patch was evaluated based on area, thickness, resistance to fracture, bioadhesion, and post-wetting bioadhesion of the adhesive film. In addition, release studies were conducted on the reservoir-type transdermal patch. The characterization tests were for i) an impermeable film with an area of 247 ± 0.19 cm2, a thickness of 0.22 ± 0.01 mm, and tensile strength of 1463.9 ± 300.30 gf; ii) an adhesive film with a tensile strength of 64.21± 18.74 gf, bio-adhesion of 879.71±205.67 gf, and a post-wetting bio-adhesion of 505.10±34.39 gf; and finally, iii) dexamethasone gel with a relative density value of 0.938±0.01, non-Newtonian fluid, 99.06% of drug content, dexamethasone release test adjusted to the zero-order kinetic model and skin permeation studies with a Flux (Jss) =140.98 μg/cm2*h. As a result of these tests, the reservoir type transdermal patch presents adequate characteristics for dexamethasone transdermal administration.

3D-Printed Polypyrrole Microneedle Arrays for Electronically Controlled Transdural Drug Release

After the spinal cord injury, inflammation and cytotoxicity cause further damage to neural cells. The progression of this secondary injury might be reduced by the administration of anti-inflammatory drugs. To allow the local delivery of such drugs while minimizing dural opening, we have created a polypyrrole (PPy)-coated microneedle array using a microscale three-dimensional (3D) printing technology that facilitates electronically controlled encapsulation and the transdural release of drugs. PPy microneedles demonstrated an electronically controlled release of steroid dexamethasone (Dexa) in a novel in vitro transdural model and in vivo. The biological activity of the device was then tested by the electronic release of Dexa into an in vitro model of neuroinflammation, using activated microglia. Following electrically activated Dexa release, inflammation was reduced, as demonstrated by a decrease in nitric oxide and proinflammatory cytokines Il-6 and MCP-1. These results demonstrate the feasibility of PPy-coated microneedles for the transdural delivery of anti-inflammatory drugs to the central nervous system.