Release Of Dexamethasone Research Articles

Dexamethasone-loaded keratin films for ocular surface reconstruction

Amniotic membrane (AM) is often applied as a substitute material during ocular surface reconstruction. However, since AM has several disadvantages, alternative materials must be considered for this application. Keratin films made from human hair (KFs) have previously been presented as a promising option; they exhibited suitable characteristics and satisfactory biocompatibility in an in vivo rabbit model. Nevertheless, dexamethasone (DEX) eye drops are necessary after surgery to suppress inflammation. Since eye drops must be administered frequently, this might result in poor patient compliance, and the release of DEX at the transplant site would be clinically beneficial. Therefore, we aimed to incorporate DEX into KFs without hindering the positive film characteristics. Drug-loaded KFs were generated either by suspension technique or by the addition of solubilizing agents. The resulting specimens were analyzed regarding appearance, loading capacity, transparency, mechanical characteristics, swelling behavior and in vitro release. Furthermore, biocompatibility was assessed in vitro by determining the cell viability, seeding efficiency and growth behavior of corneal epithelial cells. The amount of incorporated DEX influenced the transparency and biomechanical properties of the films, but even highly loaded films showed properties similar to those of AM. The suspension technique was identified as the best incorporation approach regarding chemical stability and prolonged DEX release. Moreover, suspended DEX in the films did not negatively impact cell seeding efficiencies, and the cell-growth behaviors on the specimens with moderate DEX loads were satisfactory. This suggest that these films could comprise a suitable alternative material with additional anti-inflammatory activity for ocular surface reconstruction.Graphical

Simultaneous Release of Aflibercept and Dexamethasone from an Ocular Drug Delivery System

Purpose Intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) are the current standard of care for patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). There is a growing subset of patients that does not respond to anti-VEGF monotherapy treatment. Some patients, however, do respond to combination therapy of corticosteroids and anti-VEGF. This treatment requires monthly/bimonthly injections of anti-VEGF and semi-annual injections of corticosteroid. A drug delivery system (DDS) that simultaneously releases multiple drugs could benefit these patients by reducing the number of injections. The purpose of this study was to characterize the simultaneous release of aflibercept and dexamethasone from a biodegradable microparticle- and nanoparticle-hydrogel DDS. Methods Dexamethasone-loaded nanoparticles and aflibercept-loaded microparticles were created using modified single- and double-emulsion techniques, respectively. Then, microparticles and nanoparticles were embedded into a thermoresponsive, biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate (PEG-PLLA-DA)-N-isopropylacrylamide (NIPAAm) hydrogel DDS. Drug release studies and characterization of DDS were conducted with varying doses of microparticles and nanoparticles. Results The combination aflibercept-loaded microparticle- and dexamethasone-loaded nanoparticle- hydrogel (Combo-DDS) achieved a total release time of 224 days. Small decreases were seen in swelling ratio and equilibrium water content for Combo-DDS compared to monotherapy aflibercept-loaded microparticle-hydrogel DDS (AFL-DDS) and monotherapy dexamethasone-loaded nanoparticle-hydrogel DDS (DEX-DDS). Bioactivity of aflibercept was maintained in Combo-DDS compared to AFL-DDS. Conclusions The Combo-DDS was able to extend and control the release of both aflibercept and dexamethasone simultaneously from a single DDS. This may eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for wet AMD patients.

PLLA Coating of Active Implants for Dual Drug Release

Cochlear implants, like other active implants, rely on precise and effective electrical stimulation of the target tissue but become encapsulated by different amounts of fibrous tissue. The current study aimed at the development of a dual drug release from a PLLA coating and from the bulk material to address short-term and long-lasting release of anti-inflammatory drugs. Inner-ear cytocompatibility of drugs was studied in vitro. A PLLA coating (containing diclofenac) of medical-grade silicone (containing 5% dexamethasone) was developed and release profiles were determined. The influence of different coating thicknesses (2.5, 5 and 10 µm) and loadings (10% and 20% diclofenac) on impedances of electrical contacts were measured with and without pulsatile electrical stimulation. Diclofenac can be applied to the inner ear at concentrations of or below 4 × 10−5 mol/L. Release of dexamethasone from the silicone is diminished by surface coating but not blocked. Addition of 20% diclofenac enhances the dexamethasone release again. All PLLA coatings serve as insulator. This can be overcome by using removable masking on the contacts during the coating process. Dual drug release with different kinetics can be realized by adding drug-loaded coatings to drug-loaded silicone arrays without compromising electrical stimulation.

Understanding dexamethasone kinetics in the rabbit tear fluid: Drug release and clearance from solution, suspension and hydrogel formulations

Rapid precorneal loss of topically applied eye drops limits ocular drug absorption. Controlling release and precorneal residence properties of topical formulations may improve ocular drug bioavailability and duration of action. In this study, we evaluated in vivo ocular pharmacokinetics of dexamethasone in rabbits after application of a drug solution (0.01%), suspension (Maxidex® 0.1%), and hydrogels of 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AAc) copolymers. The rabbits received a single eyedrop (solution or suspension) or dexamethasone-loaded hydrogel topically. Dexamethasone in tear fluid was sampled with glass capillaries and quantitated by LC-MS/MS. Higher dexamethasone exposure (AUC) in the tear fluid was observed with the suspension (≈3.6-fold) and hydrogel (12.8-fold) as compared to the solution. During initial 15 min post-application, the highest AUC of dissolved dexamethasone was seen after hydrogel application (368 min*µg/mL) followed by suspension (109.9 min*µg/mL) and solution (28.7 min*µg/mL. Based on kinetic simulations, dexamethasone release from hydrogels in vivo and in vitro is comparable. Our data indicate that prolonged exposure of absorbable dexamethasone in tear fluid is reached with hydrogels and suspensions. Pharmacokinetic understanding of formulation behavior in the lacrimal fluid helps in the design of dexamethasone delivery systems with improved ocular absorption and prolonged duration of action.

Design and optimization of ROS-reactive nanocarriers for controlled release of dexamethasone and real-time inhibition of mast cell activation

Upon activation, mast cells release many mediators, including reactive oxygen species (ROS) and tumor necrosis factor (TNF) orchestrating allergic inflammation. Nanocarriers (NCs) that can detect mast cell activation and respond by releasing anti-inflammatory compounds in real-time, would and effective therapy.

Drug infused Al2O3-bioactive glass coatings toward the cure of orthopedic infection

A unique implant coated substrate with dual-drug-eluting system exhibiting antibacterial, anti-inflammatory, and bone regenerative capacity has been fabricated using spray pyrolysis deposition (SPD) method. Bioglass (BG) and BG-alumina (BG-Al) composites coatings with different concentrations of Al incorporated on BG network over the Cp-Ti substrate were fabricated using SPD technique. Phase purity of BG and BG-Al composites were analyzed by XRD in which Na2Ca2Si3O9 and β-Na2Ca4(PO4)2SiO4) and Na7.15(Al7.2Si8.8O32) phases were formed. Surface morphology of the coated substrates was analyzed by SEM. Uniformity of the coatings were evaluated by surface profilometer and the uniform distribution the nanoparticles were confirmed with Elemental mapping. Systematically, each apatite layer formation on coated substrate was confirmed by immersing the samples for 1, 3, and 7days in simulated body fluid and the needle-like structure was characterized using SEM. Cumulative release of Tetracycline hydrochloride (Tet) antibiotic and Dexamethasone (Dex) anti-inflammatory drug-loaded BG-Al and BG-Al composite-coated substrate were studied for 24h. Antibacterial activity of the coated substrates were evaluated by time-dependent growth inhibition and minimal inhibitory concentration (MIC) assays in which BG-Al and BG-Al composite loaded with Tet showed considerable growth inhibition against S. aureus. Osteoblast-like cells (MG-63) exhibited profound proliferation with no cytotoxic effects which was due to release of Dex drug-coated substrates. Thus, surface modification of Cp-Ti substrate with BG, BG-Al composites coatings loaded with Tet and Dex drug can be considered for post-operative orthopedic implant infection application.

Long-Term Release of Dexamethasone With a Polycaprolactone-Coated Electrode Alleviates Fibrosis in Cochlear Implantation.

Cochlear implantation (CI) is the major treatment for severe sensorineural hearing loss. However, the fibrotic tissue forming around the electrodes reduces the treatment effectiveness of CI. Dexamethasone (DEX) is usually applied routinely in perioperative treatment of cochlear implantation (CI), but its diffusion in the inner ear after systemic administration is limited. In the present study, an electrode coated with polycaprolactone (PCL) loaded with dexamethasone was developed with a simple preparation process to maintain the stability of the electrode itself. The DEX-loaded PCL coating has good biocompatibility and does not change the smoothness, flexibility, or compliance of the implant electrode. Stable and effective DEX concentrations were maintained for more than 9 months. Compared with the pristine electrode, decreasing intracochlear fibrosis, protection of hair cells and spiral ganglion cells, and better residual hearing were observed 5 weeks after PCL-DEX electrode implantation. The PCL-DEX electrode has great potential in preventing hearing loss and fibrosis by regulating macrophages and inhibiting the expression of the fibrosis-related factors IL-1β, TNF-α, IL-4, and TGF-β1. In conclusion, the PCL-DEX electrode coating shows promising application in CI surgery.

A hydrogel based quasi-stationary test system for in vitro dexamethasone release studies for middle ear drug delivery systems

Abstract For the investigation of in vitro drug release, methods have been used in which samples of drug delivery systems are immersed in release medium. The medium is used to measure drug concentration via chromatography or photometry. These systems are suitable to investigate the drug release of different systems or to simulate tissue environments. When considering predominantly humid regions, e.g. for drug release into the cochlea through the round window membrane by a drug delivery system placed at that membrane, reproducible in vitro determination of drug release becomes particularly challenging. In this study the development of a system is reported that allows the investigation of the in vitro drug release simulating such conditions. The presented test system consists of an alginate hydrogel in glass vials simulating the biological membrane, which separates the drug delivery system from the medium filled compartment. Saline is used as release medium and injected under the hydrogel. The samples are placed on top of the hydrogel, which slightly contacts the medium surface. The drug concentration in the release medium was determined by HPLC measurements. This system allows for testing the release of dexamethasone without the samples being completely surrounded by medium. The hydrogel mediates the diffusion of the drug by ensuring the contact with the medium. Release was monitored for more than 23 days. The presented concept was successfully designed and manufactured. The system is inexpensive and can be duplicated easily. In this study, it was used to monitor the drug release of dexamethasone from PEGDA700 derived polymer. One challenge that remains to be considered is the low mechanical stability of the hydrogel, which results in a need for repeated manufacturing during the handling of the system.

Porous silicon nitride–based drug delivery carrier

AbstractTetracalcium phosphate/monetite biocement was modified with the addition of 30 wt% highly porous silicon nitride/α‐tricalcium phosphate (α‐TCP) microgranules. The volume ratio of Si3N4 and α‐TCP in microgranules was 1:1 and showed good in vitro simulated body fluid bioactivity with precipitation of hydroxyapatite particles. The intention of addition of microgranules to the biocement was to have a carrier of drug, which can be released into the body in due time. Granules prepared by the freeze granulation of starting mixture of silicon nitride and calcium phosphate and subsequent sintering at 1100°C have a suitable pore structure for the foreseen use. The pore volume was almost 1000 mm3/g with the open porosity of 77 vol%. This porosity and the biocompatible composition of silicon nitride–based granules gave a chance to fabricate a suitable composite cement for dexamethasone (DMZ) drug release into the human body. An accelerated release of dexamethasone from composite cement was observed and the full amount of DMZ was released from the composite biocement after 10 days. The presented results are a good base to adjust the total drug release time by the mixing of an appropriate amount of drug infiltrated ceramic granules with the tetracalcium phosphate/monetite cement.

Influence of sterilization on the drug release behaviour of drug coated silicone

Abstract Sterilization processes ensure sterility of drug delivery systems, but may negatively affect the properties of biomaterials and incorporated drugs by changing their physical, chemical, mechanical properties and drug release behaviour. Therefore, it is important to investigate their influence. In this study, the influence of ethylene oxide (EtO) sterilization on the drug loading and release behaviour of incorporated Diclofenac (DCF) in a Poly-L-lactide (PLLA) coating and Dexamethasone (DMS) in the silicone carrier is presented. Silicone samples containing DMS were coated with PLLA containing DCF varying in layer thickness (5, 10, and 20 μm). Half of the samples underwent EtO sterilization, the other half was not sterilized. All un-/sterilized sample surfaces were in view of the morphology and hydrophilicity examined. Furthermore, in vitro release studies of DMS and DCF were conducted. The sterilized sample surfaces showed no morphological and hydrophilicity changes. The DCF and DMS loadings were similar for the sterile and untreated samples. This also applied to the in vitro DMS release profiles apart from the end of the studies where slight differences were evident. The results indicate that both drugs loaded in the polymer coating and the silicone were not impaired by the sterilization process. Thus, EtO sterilization appears suitable for DMS containing silicone and DCF incorporated PLLA coatings as a dual drug delivery system.

3D Printed Punctal Plugs for Controlled Ocular Drug Delivery.

Dry eye disease is a common ocular disorder that is characterised by tear deficiency or excessive tear evaporation. Current treatment involves the use of eye drops; however, therapeutic efficacy is limited because of poor ocular bioavailability of topically applied formulations. In this study, digital light processing (DLP) 3D printing was employed to develop dexamethasone-loaded punctal plugs. Punctal plugs with different drug loadings were fabricated using polyethylene glycol diacrylate (PEGDA) and polyethylene glycol 400 (PEG 400) to create a semi-interpenetrating network (semi-IPN). Drug-loaded punctal plugs were characterised in terms of physical characteristics (XRD and DSC), potential drug-photopolymer interactions (FTIR), drug release profile, and cytocompatibility. In vitro release kinetics of the punctal plugs were evaluated using an in-house flow rig model that mimics the subconjunctival space. The results showed sustained release of dexamethasone for up to 7 days from punctal plugs made with 20% w/w PEG 400 and 80% w/w PEGDA, while punctal plugs made with 100% PEGDA exhibited prolonged releases for more than 21 days. Herein, our study demonstrates that DLP 3D printing represents a potential manufacturing platform for fabricating personalised drug-loaded punctal plugs with extended release characteristics for ocular administration.

Assessment of structural, biological and drug release properties of electro-sprayed poly lactic acid-dexamethasone coating for biomedical applications.

The efficacy of an implant is highly depends on its coating characteristics mainly determined by polymer properties and coating technique. Electro-spraying is an inexpensive and versatile coating technique with various advantages for biomedical application. In this study, the efficacy of electro-sprayed (ES) poly lactic acid (PLA)-dexamethasone (DEX) coatings for medical implants was evaluated and compared with spin-coated samples as control. Structural properties of coatings were investigated using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Confocal and scanning electron microscopy (SEM), contact angle measurement and nanoindentation tests were used to study surface properties. Coating degradation rate and drug release profile were studied for 40days. Cell viability experiments were also performed on human endothelial (HUVEC) and smooth muscle cells (HUASMC) using MTT assay and SEM. XRD and DSC analysis showed electro-spraying significantly reduce PLA and DEX crystallinity. Surface studies showed ES coatings has significantly higher hydrophobicity and roughness with microbead-nanofiber morphology vs. micro-nanoporous structure of spin-coated samples. Initial burst release of DEX was 22% and 10% after 6h and total release was 71% and 46% after 40days for ES and spin-coated samples, respectively. HUVEC viability of ES samples was higher than spin-coated ones after 1 and 4days. However, dexamethasone release profile reduced HUASMC proliferation in ES PLA-DEX samples in comparison to spin-coated after 1 and 3days. In conclusion, in vitro results showed potential of ES PLA-DEX as a biocompatible and efficient anti-inflammatory coating with suitable drug release profile for future applications such as coronary drug eluting stents.

Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments.

Engineering multifunctional hydrogel systems capable of amplifying the regenerative capacity of endogenous progenitor cells via localized presentation of therapeutics under tissue inflammation is central to the translation of effective strategies for hard tissue regeneration. Here, we loaded dexamethasone (DEX), a pleotropic drug with anti-inflammatory and mineralizing abilities, into aluminosilicate clay nanotubes (halloysite clay nanotubes (HNTs)) to engineer an injectable multifunctional drug delivery system based on photo-cross-linkable gelatin methacryloyl (GelMA) hydrogel. In detail, a series of hydrogels based on GelMA formulations containing distinct amounts of DEX-loaded nanotubes was analyzed for physicochemical and mechanical properties and kinetics of DEX release as well as compatibility with mesenchymal stem cells from human exfoliated deciduous teeth (SHEDs). The anti-inflammatory response and mineralization potential of the engineered hydrogels were determined in vitro and in vivo. DEX conjugation with HNTs was confirmed by FTIR analysis. The incorporation of DEX-loaded nanotubes enhanced the mechanical strength of GelMA with no effect on its degradation and swelling ratio. Scanning electron microscopy (SEM) images demonstrated the porous architecture of GelMA, which was not significantly altered by DEX-loaded nanotubes' (HNTs/DEX) incorporation. All GelMA formulations showed cytocompatibility with SHEDs (p < 0.05) regardless of the presence of HNTs or HNTs/DEX. However, the highest osteogenic cell differentiation was noticed with the addition of HNT/DEX 10% in GelMA formulations (p < 0.01). The controlled release of DEX over 7 days restored the expression of alkaline phosphatase and mineralization (p < 0.0001) in lipopolysaccharide (LPS)-stimulated SHEDs in vitro. Importantly, in vivo data revealed that DEX-loaded nanotube-modified GelMA (5.0% HNT/DEX 10%) led to enhanced bone formation after 6 weeks (p < 0.0001) compared to DEX-free formulations with a minimum localized inflammatory response after 7 days. Altogether, our findings show that the engineered DEX-loaded nanotube-modified hydrogel may possess great potential to trigger in situ mineralized tissue regeneration under inflammatory conditions.

Targeted-lung delivery of dexamethasone using gated mesoporous silica nanoparticles. A new therapeutic approach for acute lung injury treatment

Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage. TNFR-Dex-MSNs nanoparticles are preferentially internalized by pro-inflammatory macrophages, which overexpressed the TNFR1 receptor, with the subsequent cargo release upon the enzymatic hydrolysis of the capping peptide in lysosomes. Moreover, TNFR-Dex-MSNs are able to reduce the levels of TNF-α and IL-1β cytokines in activated pro-inflammatory M1 macrophages. The anti-inflammatory effect of TNFR-Dex-MSNs is also tested in an in vivo ALI mice model. The administered nanodevice (intravenously by tail vein injection) accumulated in the injured lungs and the controlled dexamethasone release reduces markedly the inflammatory response (TNF-α IL-6 and IL-1β levels). The attenuation in lung damage, after treatment with TNFR-Dex-MSNs, is also confirmed by histopathological studies. Besides, the targeted-lung dexamethasone delivery results in a decrease of dexamethasone derived side-effects, suggesting that targeted nanoparticles can be used for therapy in ALI and could help to overcome the clinical limitations of current treatments.

Shape-Defined microPlates for the Sustained Intra-articular Release of Dexamethasone in the Management of Overload-Induced Osteoarthritis.

Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 μm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (μPLs) are created and intra-articularly deposited for the sustained release of DEX. Under confined conditions, DEX release is projected to persist for several months, with only ∼20% released in the first month. In a highly rigorous murine knee overload injury model (post-traumatic osteoarthritis), a single intra-articular injection of Cy5-μPLs is detected in the cartilage surface, infrapatellar fat pad/synovium, joint capsule, and posterior joint space up to 30 days. One intra-articular injection of DEX-μPL (1 mg kg–1) decreased the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and matrix metalloproteinase (MMP)-13 by approximately half compared to free DEX at 4 weeks post-treatment. DEX-μPL also reduced load-induced histological changes in the articular cartilage and synovial tissues relative to saline or free DEX. In sum, the μPLs provide sustained drug release along with the capability to precisely control particle geometry and mechanical properties, yielding long-lasting benefits in overload-induced OA. This work motivates further study and development of particles that provide combined pharmacological and mechanical benefits.

Sequential drug release of co-assembled supramolecular hydrogel as synergistic therapy against Staphylococcus aureus endophthalmitis

Although endophthalmitis is a serious sight-threatening disorder, combining anti-inflammatory agents and antibiotics has provided new methods for effectively controlling it. This paper reports that the co-assembly of a sparingly soluble antibiotic (levofloxacin; Lev) and dexamethasone-peptide amphiphile (Dex-SA-RGD) instantly generates a macroscopically supramolecular hydrogel (Lev/Dex-SA-RGD) without any external stimulus under physiological conditions, which could be used in synergistic therapy to cure endophthalmitis induced by Staphylococcus aureus (i.e., S. aureus). The resulting co-assembled supramolecular hydrogel was thoroughly characterized using rheology, circular dichroism, and transmission electron microscopy. An in vitro drug release study showed that Lev was rapidly released from the supramolecular hydrogel within 6 h, while Dex-SA-RGD escaped from the supramolecular hydrogel as a result of matrix erosion, and then acted as a prodrug to provide the sequentially slow release of active dexamethasone via the hydrolytic route. The Lev/Dex-SA-RGD supramolecular hydrogel showed high antibacterial activities against both gram-negative and gram-positive strains. Moreover, a rabbit endophthalmitis model induced by S. aureus showed that the intravitreal injection of the Lev/Dex-SA-RGD supramolecular hydrogel resulted in excellent therapeutic efficacy with no apparent damage or destruction of the retina, and dramatically suppressed inflammatory responses (e.g., leukocyte and lymphocyte infiltration, microglial activation, cytokine production, and retinal cell death). As a rational approach to investigate and apply the co-assembled hydrogel, this work presents the potential of synergistic intervention to prevent retinal tissue damage and vision impairment, and ultimately shows the clinical benefits of using supramolecular hydrogels for ocular drug delivery.

Kaempferol loaded albumin nanoparticles and dexamethasone encapsulation into electrospun polycaprolactone fibrous mat – Concurrent release for cartilage regeneration

Sustained release of bioactive molecules promoting proliferation of chondrocytes, differentiation and deposition of collagen and glycosaminoglycans is advantageous for cartilage tissue engineering. In this study, Kaempferol was encapsulated into albumin nanoparticle, which was added to polycaprolactone solution containing dexamethasone and electrospun to obtain nanofibrous mats. Herein, three different concentrations of kaempferol loaded albumin nanoparticles (KNP) (2 mg/ml, 4 mg/ml, 6 mg/ml) were added to fixed concentration of dexamethasone (2 mg/ml). Field emission scanning electron microscopic (FESEM) images implied a decrease in fiber diameter range with an increase in weight of KNP. XRD analysis revealed amorphization of both the drugs which is beneficial for drug delivery applications. Further, drug release study showed sustained release of kaempferol and dexamethasone for 15 days with initial burst release. Also, increased release of kaempferol from the mats was observed in dexamethasone added groups compared to KNP added groups. In addition, in vitro evaluation of fabricated mats with human chondrocytes induced increased deposition of glycosaminoglycans showing non cytotoxicity as well as pro chondrogenic property. To summarize, this model of nanofibrous mat releasing sustained concentrations of kaempferol and dexamethasone seems to be beneficial for cartilage regeneration.

Simultaneous quantification of dexamethasone and 6β-hydroxydexamethasone in rabbit plasma, aqueous and vitreous humor, and retina by UHPLC-MS/MS.

Aim: To develop and validate a fit for purpose method for the simultaneous determination of dexamethasone and its major metabolite, 6β-hydroxydexamethasone, in rabbit plasma and ocular matrices to measure the in vivo release and distribution profile of dexamethasone from intravitreal implants. Materials & methods: An UHPLC-MS/MS system was employed to perform the bioanalysis. The method was validated according to the USFDA Bioanalytical Method Validation Guidance for Industry. Results & conclusion: The method was found to be fit-for-purpose for the described biological matrices and had a LLOQ of 0.1ng/ml.

The Development of Polylactic Acid/Multi-Wall Carbon Nanotubes/Polyethylene Glycol Scaffolds for Bone Tissue Regeneration Application.

Composite electrospun fibers were fabricated to develop drug loaded scaffolds to promote bone tissue regeneration. Multi-wall carbon nanotubes (MWCNTs) were incorporated to polylactic acid (PLA) to strengthen electrospun nanofibers. To modulate drug release behavior, different ratios of hydrophilic polyethylene glycol (PEG) were added to composite fibers. Glass transition temperature (Tg) can be reduced by the incorporated PEG to enhance the ductility of the nanofibers. The SEM images and the MTT results demonstrated that composite fibers are suitable scaffolds for cell adhesion and proliferation. Dexamethasone (DEX), an osteogenic inducer, was loaded to PLA/MWCNT/PEG fibers. The surface element analysis performed by XPS showed that fluorine of DEX in pristine PLA fibers was much higher than those of the MWCNT-containing fibers, suggesting that the pristine PLA fibers mainly load DEX on their surfaces, whereas MWCNTs can adsorb DEX with evenly distribution in nanofibers. Drug release experiments demonstrated that the release profiles of DEX were manipulated by the ratio of PEG, and that the more PEG in the nanofibers, the faster DEX was released. When rat bone marrow stromal cells (rBMSCs) were seeded on these nanofibers, the Alizarin Red S staining and calcium quantification results demonstrated that loaded DEX were released to promote osteogenic differentiation of rBMSCs and facilitate mineralized tissue formation. These results indicated that the DEX-loaded PLA/MWCNT/PEG nanofibers not only enhanced mechanical strength, but also promoted osteogenesis of stem cells via the continuous release of DEX. The nanofibers should be a potential scaffold for bone tissue engineering application.

Preparation and in-vitro evaluation of β-CD/HA nanocomposite as a potential carrier for hydrophobic drugs.

This study aimed to provide a new drug delivery system for hydrophobic compounds. Dexamethasone (DEX) was employed as a hydrophobic model drug, which incorporated into the network of hydroxyapatite (HA)/Cyclodextrin (β-CD) nanocomposite. Phase analysis, chemical bonding, morphology, and drug release was evaluated using XRD, FTIR, FESEM, and UV-vis spectroscopy, respectively. XRD patterns showed the formation of the crystalline structure and FTIR analysis showed the chemical bonding between organic and inorganic phases. FESEM images accompanied by EDX analysis confirmed the presence of HA nano-flakes. Release of DEX loaded β-CD/HA was measured to be around 4.6% and 18.7% in pH5.3 and pH 7.4, respectively. In conclusion, the prepared system could be a potential pH sensitive carrier for sustainable release of water-insoluble drugs.