Permeability of triamcinolone acetonide, released from mucoadhesive films, through a buccal mucosa-mimetic barrier: Permeapad™.

OBJECTIVES: The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed. METHODS: Three TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer. RESULTS: 45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA's permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., ∼28 % for monolayer film to ∼10 % for bilayer film, F1). SIGNIFICANCE: The mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus.

In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye.

This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153 nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.

Nanodelivery of triamcinolone acetonide with PLGA-chitosan nanoparticles for the treatment of ocular inflammation.

Triamcinolone acetonide (TA) is widely indicated in the treatment of several ocular disorders, but the free drug suspension limits its clinical benefits and commercial compositions cause adverse ocular effects. In this study, TA was formulated in poly(d,l-lactide-co-glycolide) (PLGA)-chitosan (PLC) nanoparticles (NPs) for the treatment of ocular inflammatory diseases. TA-loaded PLC NPs exhibited excellent anti-inflammatory activity against human corneal epithelial (HCE) cells and significantly reduced the secretion of interleukin (IL)-6 in tumour necrosis factor (TNF)-α activated cells. In a rabbit model, TA-loaded PLC NPs did not show any typical clinical signs of eye inflammation and significantly alleviated inflammatory signs, compared with free TA suspension, at 24 h after a single dose. TA-loaded PLC NPs exhibited a greater aqueous humour transparency (%AHT), compared with that of normal saline (NS) or free TA suspension, indicating reduction in anterior chamber fogginess. Pharmacokinetic analysis of rabbit eyes revealed that TA-loaded PLC NPs peaked at 6 h. Substantial concentrations of TA were observed until 24 h, indicating the superiority of this PLC-based nanocarrier system. Overall, PLC-based NP formulations offer a new approach for the treatment of ocular inflammatory diseases.

Triamcinolone acetonide loaded-cationic nano-lipoidal formulation for uveitis: Evidences of improved biopharmaceutical performance and anti-inflammatory activity.

Topical administration of corticosteroids is the cornerstone treatment of anterior uveitis, but poor corneal penetration and retention cause hindrance in their therapeutic utility. The conventional eye drops are less valuable in conditions where inflammation reaches deeper regions of the eye. Therefore, there is a clear need for an effective drug delivery system, which can increase corticosteroid penetration after topical application. To address this, cationic nanostructured lipid carriers of the drug triamcinolone acetonide (cTA-NLC) were prepared. The cTA-NLC were prepared by a hot microemulsion method and evaluated for drug release, permeation, cell uptake, cytotoxicity, anti-inflammatory activity and ocular irritancy. The cTA-NLC are nanometric in size (< 200 nm), with a zeta potential of about +35 mv and % drug EE of 88 %. The nanocarriers exhibited slow and sustained release of around 84 % in 24 h and transcorneal drug permeation of 51 % in 8 h. The nanocarriers exhibited no cytotoxicity (% cell viability of>90 %). The cell uptake study showed that nanocarriers could retain inside the cells for 24 h. The developed formulation could significantly reduce the TNF-α level in LPS induced inflamed cells. The studies indicated that cTA-NLC could be a promising option for the topical treatment of uveitis.

Dilution and microfiltration of particulate corticosteroids for spinal epidural injections: impact on drug concentration and agglomerate formation.

Particulate corticosteroids have been described to lead to greater pain improvement compared with their non-particulate counterparts when used in epidural injections. It is hypothesised that filtering may significantly impact their concentration and long-term efficacy. We investigated if passing particulate suspensions through different commonly-used filters affects drug dosage. Two particulate corticosteroid formulations, triamcinolone acetonide and methylprednisolone acetate, were mixed at different concentrations with either bupivacaine hydrochloride or 0.9% sodium chloride. Solutions were passed through a 5-µm and a 0.2-µm filter. Mass spectroscopy results indicated a complete loss of corticosteroid from the solutions using both filters, and light microscopy imaging demonstrated agglomerate formation, suggesting that filtering interferes with drug dosage. The choice of diluents must also be considered to reduce large agglomerate formation. Clinicians should be aware of the consequences of filtering particulate suspensions and carefully consider the selection of diluent when considering treatment plans.

Kenalog modified by ionizing radiation induces intrinsic apoptosis mediated by elevated levels of reactive oxygen species in melanoma cancer.

Kenalog is a synthetic glucocorticoid drug used to treat various cancers including ocular and choroidal melanoma. However, the drug achieves rarely sustainable results for patients. To overcome this difficulty, the structure of Kenalog was altered by ionizing radiation (IR) to develop a more effective anticancer agent for treatment of various skin cancers. The anticancer effect of modified Kenalog (Kenalog­IR) was assessed in melanoma cancer cells in vitro. The assessment of mitochondrial functions by MTT assay revealed significant inhibition of melanoma cancer cell viability by Kenalog­IR compared to Kenalog. Moreover, Kenalog­IR­induced apoptotic cell death was associated with the intrinsic mitochondrial pathway by triggering the release of intrinsic apoptosis molecules through activation of caspase­related molecules in concentration and time­dependent manners. Furthermore, it was observed that Kenalog­IR­induced apoptosis was associated with the generation of reactive oxygen species (ROS) with increased G2/M cell cycle arrest. Collectively, Kenalog­IR may be a potential suppressor of skin­related cancer in particular melanoma cancer.

Microemulsion-based delivery of triamcinolone acetonide to posterior segment of eye using chitosan and butter oil as permeation enhancer: an in vitro and in vivo investigation.

The aim of the study was to formulate a microemulsion (ME) using chitosan (CH) and the butter oil (BO) as a permeation enhancer for targeting drug to the posterior segment of the eye, via topical route. Triamcinolone acetonide (TA) was selected as the model drug since it undergoes extensive first-pass metabolism, leading to poor oral bioavailability of 23%. For optimisation of BO concentration, different ratios of TA:BO were prepared by simple physical mixing in the ratio of 1:9 to 9:1 and diffusion study was performed. MEs containing TA, TA:BO and TA CH ME were formulated by water titration method. Globule sizes of TA ME, TA:BO ME and TA CH ME were found to be 66.06 ± 0.32 nm, 78.52 ± 1.50 nm and 97.30 ± 2.50 nm, respectively. In ex vivo diffusion studies using goats eye, TA:BO ME (31.33 ± 0.46 and 33.98 ± 0.23) and TA CH ME (24.10 ± 0.41 and 27.00 ± 0.18) showed higher percentage of drug diffusion in comparison to TA ME (13.29 ± 0.41and 15.56 ± 0.34) and TA solution (8.20 ± 1.04 and 10.39 ± 0.22) in presence and in absence of vitreous humour. Fluorescence intensity of coumarin-6 (as a marker) loaded ME with BO and CH was found to be higher, confirming their role in altering membrane permeability and facilitating coumarin-6 diffusion to the posterior chamber. Overall, it was concluded that BO enhances the bioavailability of TA across the retina, thereby proving its potential as permeation enhancer in facilitating drug delivery to the posterior segment of the eye.

A Comparison of Characteristic Properties and Qualitative Difference between Three Kinds of Triamcinolone Acetonide.

OBJECTIVE: To conduct a study comparing 3 triamcinolone acetonide preparations in terms of their particle surface observed with a scanning electron microscope, their particle size distribution, and sedimentation in order to discuss their ability to facilitate visualization during vitreous surgery and the clinical results. METHODS: Kenacort-A®, the newer form of MaQaid, and the older form of MaQaid® were used. A scanning electron microscope and a measuring device were used. Sedimentation was measured based on ultraviolet and visible light absorption spectra. RESULTS: Observation of the particle surface revealed that small particles of the older form of MaQaid® had clumped together, and they contained numerous voids. It had a small mean particle dia (almost the same size as the newer form of MaQaid® and Kenacort-A). Kenacort-A was dispersed while the older form of MaQaid® had numerous clumps and ascending particles, and a large sedimentation volume. Small sedimentation volume and few clumps were noted on the newer form of MaQaid®. CONCLUSION: The newer form of MaQaid® had a particle distribution like that of Kenacort-A®, so it should provide good visibility. Moreover, it is free of preservatives, so it may prove to be a useful aid to visualize the vitreous during vitreous surgery.

Polyamidoamine dendrimer-conjugated triamcinolone acetonide attenuates nerve injury-induced spinal cord microglia activation and mechanical allodynia.

Background Accumulating evidence on the causal role of spinal cord microglia activation in the development of neuropathic pain after peripheral nerve injury suggests that microglial activation inhibitors might be useful analgesics for neuropathic pain. Studies also have shown that polyamidoamine dendrimer may function as a drug delivery vehicle to microglia in the central nervous system. In this regard, we developed polyamidoamine dendrimer-conjugated triamcinolone acetonide, a previously identified microglial activation inhibitor, and tested its analgesic efficacy in a mouse peripheral nerve injury model. Result Polyamidoamine dendrimer was delivered selectively to spinal cord microglia upon intrathecal administration. Dendrimer-conjugated triamcinolone acetonide inhibited lipoteichoic acid-induced proinflammatory gene expression in primary glial cells. In addition, dendrimer-conjugated triamcinolone acetonide administration (intrathecal) inhibited peripheral nerve injury-induced spinal cord microglial activation and the expression of pain-related genes in the spinal cord, including Nox2, IL-1ß, TNF-α, and IL-6. Dendrimer-conjugated triamcinolone acetonide administration right after nerve injury almost completely reversed peripheral nerve injury-induced mechanical allodynia for up to three days. Meanwhile, dendrimer-conjugated triamcinolone acetonide administration 1.5 days post injury significantly attenuated mechanical allodynia. Conclusion Our data demonstrate that dendrimer-conjugated triamcinolone acetonide inhibits spinal cord microglia activation and attenuates neuropathic pain after peripheral nerve injury, which has therapeutic implications for the treatment of neuropathic pain.

Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

Validation of a cage implant system for assessing in vivo performance of long-acting release microspheres.

Here we describe development of a silicone rubber/stainless steel mesh cage implant system, much like that used to assess biocompatibility of biomaterials [1], for easy removal of injectable polymer microspheres in vivo. The sterile cage has a type 316 stainless steel mesh size (38 µm) large enough for cell penetration and free fluid flow in vivo but small enough for microsphere retention, and a silicone rubber shell for injection of the microspheres. Two model drugs, the poorly soluble steroid, triamcinolone acetonide, and the highly water-soluble luteinizing hormone-releasing hormone (LHRH) peptide superagonist, leuprolide, were encapsulated in PLGA microspheres large enough (63-90 µm) to be restrained by the cage implant in vivo. The in vitro release from both formulations was followed by ultra-performance liquid chromatography (UPLC) with and without the cage in a standard release media, PBS pH 7.4 + 0.02% Tween 80 + 0.05% sodium azide, at 37 °C. Pharmacokinetics (PK) in rats was assessed after SC injection or SC in-cage implantation of microspheres with plasma analysis by LC-MS/MS or EIA. Tr-A and leuprolide in vitro release was largely unaffected after the initial burst irrespective of the cage or test tube incubation vessel and release was much slower than observed in vivo for both drugs. Moreover, Tr-A and leuprolide pharmacokinetics with and without the cage were highly similar during the 2-3 week release duration before a significant inflammatory response was caused by the cage implant. Hence, the PK-validated cage implant provides a simple means to recover and evaluate the microsphere drug carriers in vivo during a time window of at least a few weeks in order to characterize the polymer microsphere release and erosion behavior in vivo. This approach may facilitate development of mechanism-based in vitro/in vivo correlations and enable development of more accurate and useful in vitro release tests.

Comparison of the cohesion-adhesion balance approach to colloidal probe atomic force microscopy and the measurement of Hansen partial solubility parameters by inverse gas chromatography for the prediction of dry powder inhalation performance.

The abilities of the cohesive-adhesive balance approach to atomic force microscopy (AFM) and the measurement of Hansen partial solubility parameters by inverse gas chromatography (IGC) to predict the performance of carrier-based dry powder inhaler (DPI) formulations were compared. Five model drugs (beclometasone dipropionate, budesonide, salbutamol sulphate, terbutaline sulphate and triamcinolone acetonide) and three model carriers (erythritol, α-lactose monohydrate and d-mannitol) were chosen, giving fifteen drug-carrier combinations. Comparison of the AFM and IGC interparticulate adhesion data suggested that they did not produce equivalent results. Comparison of the AFM data with the in vitro fine particle delivery of appropriate DPI formulations normalised to account for particle size differences revealed a previously observed pattern for the AFM measurements, with a slightly cohesive AFM CAB ratio being associated with the highest fine particle fraction. However, no consistent relationship between formulation performance and the IGC data was observed. The results as a whole highlight the complexity of the many interacting variables that can affect the behaviour of DPIs and suggest that the prediction of their performance from a single measurement is unlikely to be successful in every case.

Physicochemical characterization and in vivo evaluation of triamcinolone acetonide-loaded hydroxyapatite nanocomposites for treatment of rheumatoid arthritis.

The current study was aimed to investigate the anti-inflammatory effect of triamcinolone acetonide-loaded hydroxyapatite (TA-loaded HAp) nanocomposites in the arthritic rat model. The HAp nanocomposites were synthesized through a chemical precipitation method and the drug was subsequently incorporated into the nanocomposites using an impregnation method. The physicochemical properties as well as cytotoxicity of the prepared nanoformulation were examined as well. To evaluate the therapeutic efficacy of the prepared nanoformulation, the various parameters such as paw volume, haematological parameters and histological studies were assessed in the arthritic rats. The nanocomposites with the particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 41.94% were obtained in this study. The specific surface area (aBET) as well as the volume of nitrogen adsorbed on one gram of HAp to complete the monolayer adsorption (Vm) were decreased after the drug loading process. The prepared nanoformulation revealed the slower drug release profile compared to the pure drug. Furthermore, the obtained data from MTT assay showed that the TA-loaded nanocomposites had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines as compared to the pure drug. Furthermore, TA-loaded HAp nanocomposites demonstrated favorable effects on the paw volume as well as the haematological and histopathological abnormalities in the adjuvant-induced arthritic rats. Therefore, TA-loaded HAp nanocomposites are potentially suggested for treatment of rheumatoid arthritis after further required evaluations.

Derivatization Strategies for the Detection of Triamcinolone Acetonide in Cartilage by Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

Osteoarthritis (OA), characterized by degeneration of the cartilaginous tissue in articular joints, severely impairs mobility in many people worldwide. The degeneration is thought to be mediated by inflammatory processes occurring in the tissue of the joint, including the cartilage. Intra-articular administered triamcinolone acetonide (TAA) is one of the drug treatments employed to ameliorate the inflammation and pain that characterizes OA. However, the penetration and distribution of TAA into the avascular cartilage is not well understood. We employed matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which has been previously used to directly monitor the distribution of drugs in biological tissues, to evaluate the distribution of TAA in human cartilage after in vitro incubation. Unfortunately, TAA is not easily ionized by regular electrospray ionization (ESI) or MALDI. To overcome this problem, we developed an on-tissue derivatization method with Girard's reagent T (GirT) in human incubated cartilage being able to study its distribution and quantify the drug abundance (up to 3.3 ng/µL). Our results demonstrate the depth of penetration of a corticosteroid drug in human OA cartilage using MALDI-MSI.

Triamcinolone acetonide nanoparticles incorporated in thermoreversible gels for age-related macular degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the US affecting millions yearly. It is characterized by intraocular neovascularization, inflammation and retinal damage which can be ameliorated through intraocular injections of glucocorticoids. However, the complications that arise from repetitive injections as well as the difficulty posed by targeting the posterior segment of the eye make this interesting territory for the development of novel drug delivery systems (DDS). In the present study, we described the development of a DDS composed of triamcinolone acetonide-encapsulated PEGylated PLGA nanoparticles (NP) incorporated into PLGA-PEG-PLGA thermoreversible gel and its use against VEGF expression characteristic of AMD. We found that the NP with mean size of 208 ± 1.0 nm showed uniform size distribution and exhibited sustained release of the drug. We also demonstrated that the polymer can be injected as a solution and transition to a gel phase based on the biological temperature of the eye. Additionally, the proposed DDS was non-cytotoxic to ARPE-19 cells and significantly reduced VEGF expression by 43.5 ± 3.9% as compared to a 1.53 ± 11.1% reduction with triamcinolone. These results suggest the proposed DDS will contribute to the development of novel therapeutic strategies for AMD.

Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-ß3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration.

Articular cartilage repair remains a challenging problem. Based on a high-throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF-ß3) strongly potentiated chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF-ß3-treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF-ß3-induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates the mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to the glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed that the mTORC1/AKT pathway and the glucocorticoid receptor was highly activated with FA and TA, but to a lesser extent with DEX. Collectively, these results show a unique ability of FA to enhance TGF-ß3-associated chondrogenesis, and suggest that the FA/TGF-ß3 combination may be used as major inducer of chondrogenesis in vitro. Additionally, FA/TGF-ß3 could be potentially applied in a clinical setting to increase the efficiency of regenerative approaches based on chondrogenic differentiation of stem cells.

Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells.

Triamcinolone acetonide (TA) is a potent, intermediate-acting, steroid that has anti-inflammatory and anti-angiogenic activity. Intravitreal administration of TA has been used for diabetic macular edema, proliferative diabetic retinopathy and exudative age-related macular degeneration (AMD). However, the hydrophobicity, lack of solubility, and the side effects limit its effectiveness in the treatment of retinal diseases. In this study, we explore a PAMAM dendrimer-TA conjugate (D-TA) as a potential strategy to improve intracellular delivery and efficacy of TA to target cells. The conjugates were prepared with a high drug payload (∼ 21%) and were readily soluble in saline. Compared to free TA, D-TA demonstrated a significantly improved toxicity profile in two important target [microglial and human retinal pigment epithelium (RPE)] cells. The D-TA was ∼ 100-fold more effective than free TA in its anti-inflammatory activity (measured in microglia), and in suppressing VEGF production (in hypoxic RPE cells). Dendrimer-based delivery may improve the efficacy of TA towards both its key targets of inflammation and VEGF production, with significant clinical implications.

Hydroxyl PAMAM dendrimer-based gene vectors for transgene delivery to human retinal pigment epithelial cells.

Ocular gene therapy holds promise for the treatment of numerous blinding disorders. Despite the significant progress in the field of viral and non-viral gene delivery to the eye, significant obstacles remain in the way of achieving high-level transgene expression without adverse effects. The retinal pigment epithelium (RPE) is involved in the pathogenesis of retinal diseases and is a key target for a number of gene-based therapeutics. In this study, we addressed the inherent drawbacks of non-viral gene vectors and combined different approaches to design an efficient and safe dendrimer-based gene-delivery platform for delivery to human RPE cells. We used hydroxyl-terminated polyamidoamine (PAMAM) dendrimers functionalized with various amounts of amine groups to achieve effective plasmid compaction. We further used triamcinolone acetonide (TA) as a nuclear localization enhancer for the dendrimer-gene complex and achieved significant improvement in cell uptake and transfection of hard-to-transfect human RPE cells. To improve colloidal stability, we further shielded the gene vector surface through incorporation of PEGylated dendrimer along with dendrimer-TA for DNA complexation. The resultant complexes showed improved stability while minimally affecting transgene delivery, thus improving the translational relevance of this platform.

Impact on intraocular pressure after 20-mg decanted triamcinolone acetonide (kenalog) injection when using prophylactic antiglaucoma therapy.

PURPOSE: To analyze intraocular pressure (IOP) response after 20-mg decanted intravitreal triamcinolone acetonide followed by early prophylactic IOP-lowering therapy. METHODS: Overall, IOP results of 120 high-dose decanted intravitreal triamcinolone acetonide injections from 58 nonglaucomatous patients with macular edema, with antiglaucoma therapy prescribed from Week 1 regardless of baseline IOP were retrospectively reviewed. RESULTS: In cases of consistent compliance with IOP-lowering drugs (79.2%), IOP increased by 2 mmHg at 4 months (P = 0.300) and returned to baseline at 6 months. In cases of noncompliance (20.8%), IOP increased by 7 mmHg at 1 month (P < 0.001) and returned to baseline after starting treatment. Multivariate regression analysis showed that nonvitrectomized eyes and noncompliance with IOP-lowering drugs were independent predictors of increase in IOP greater than 21 mmHg (P = 0.0098 and P = 0.0019, respectively). Nonvitrectomized eyes had a 46% greater chance to experience increase in IOP compared with vitrectomized ones. Poor compliance with IOP-lowering drugs lead to a 45% greater likelihood of experiencing increase in IOP compared with compliant patients. Multiple injections were not associated with the increased risk for increase in IOP greater than 21 mmHg (P = 0.273). Of 120 cases, 2 eyes (1.7%) developed uncontrolled IOP and required glaucoma surgery by 4 months, with good final IOP outcome. CONCLUSION: Twenty milligram decanted intravitreal triamcinolone acetonide can be safely used to treat macular edema in nonglaucomatous patients; IOP elevation can be adequately controlled with prophylactic antiglaucoma drugs. Noncompliance with prophylactic therapy creates an early spike in IOP, and vitreous status can significantly impact increase in IOP. Compliance with IOP-lowering drugs should be stressed to patients receiving high-dose intravitreal triamcinolone acetonide especially in cases of nonvitrectomized eyes.