Penetration Of Triamcinolone Acetonide Research Articles

Deep eutectic solvent self-assembled reverse nanomicelles for transdermal delivery of sparingly soluble drugs

BackgroundTransdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity.ResultsWe fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility.ConclusionsThe present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.

Design, optimization and characterization of novel topical formulations containing Triamcinolone Acetonide

Triamcinolone Acetonide (TA), a lipid-soluble molecule, is a synthetic glucocorticosteroid with anti-scarring, immunosuppressive and anti-inflammatory activity. The penetration of TA through the hypertrophic scar is challenging due to the scar tissue is thicker than the normal skin tissue. To overcome this problem, it was planned to prepare liposomal systems which are using for their penetration enhancer effect in topical use. So, in the present study, TA loaded liposome and liposomal film formulations were prepared and optimized to increase release and also stability. For the optimization of liposome formulations, response surface methodology (RSM) was used and the selected independent variables were the amounts of phospholipon 90g (PH) and cholesterol (CH). Encapsulation efficiency, particle size and zeta potential which were selected as dependent variables for liposome were found as 85.18% ± 2.01%, 185.2 ± 2.15 nm and −7.48 ± 0.42 mV, respectively. By using optimum liposome formulation, liposomal film formulations were prepared. The percentage of PVA ad PG were chosen as independent variables of liposomal film formulation. The dependent variables of the liposomal film formulations which were thickness, puncture strength and puncture deformation values were found to be 0.24 ± 0.02 mm, 5.53 ± 2.43 N/mm2 and 8.65% ± 1.45%, respectively. Spherical and uniform shapes of liposomes were confirmed by electron microscopy. The in-vitro bioadhesion work value of the optimum liposomal film formulation indicated that the films provide sufficient adhesion on the skin. In vitro release studies showed that the release behavior of TA from the optimized formulations fitted well with the Higuchi kinetic model. Physical stability tests demonstrated that optimized liposome and liposomal film were convenient for storage at 5 ± 3 °C for at least 90 days. In conclusion, optimized liposome and liposomal film formulations of TA could be offered as a promising strategy regarding their release, particle size, high encapsulation efficiency and stability for the treatment of hypertrophic scars.

Targeted intracorneal delivery—Biodistribution of triamcinolone acetonide following topical iontophoresis of cationic amino acid ester prodrugs

The aim was to investigate intracorneal iontophoresis of biolabile triamcinolone acetonide (TA) amino acid ester prodrugs (TA-AA). Arginine and lysine esters of TA (TA-Arg and TA-Lys, respectively) were synthesized and characterized; quantification was performed by HPLC-UV and UHPLC–MS/MS. The aqueous solubility of the prodrugs (at pH 5.5) was ∼1000-fold greater than TA. Anodal iontophoresis (10min at 3mA/cm2) of TA-AA was investigated using isolated porcine cornea. Although no statistically significant difference was observed in total intracorneal delivery of TA (468.25±59.70 and 540.85±79.16nmolTA/cm2, for TA-Arg and TA-Lys, respectively), the different susceptibilities of the prodrugs to hydrolysis influenced intracorneal biodistribution. Quantification of TA in twenty-five 40μm thick corneal lamellae revealed significantly deeper penetration of TA following TA-Lys iontophoresis. Its superior resistance to hydrolysis enabled sustained electromigration into the deeper cornea suggesting judicious prodrug selection might enable targeted regioselective drug delivery. The intracorneal biodistribution following anodal iontophoresis of TA-Arg (2.3mM; 10min, 3mA/cm2) was visualized by full field optical coherence tomography providing qualitative confirmation of the extensive intracorneal penetration of TA. Short duration iontophoresis of TA-AA prodrugs may improve deep corneal bioavailability and efficacy in vivo, constituting a “single-shot” treatment option for corneal allograft rejection.

Effect of intraocular pressure (IOP) and choroidal circulation on controlled episcleral drug delivery to retina/vitreous

Transscleral drug delivery may become a safe alternative to the intravitreal injection for chronic retinal diseases such as age-related macular degeneration or diabetic macular edema. However, the drug delivered onto the sclera subjects to vigorous clearance by episcleral and choroidal circulation; in addition, the penetration from episclera to retina needs to overcome counter-directional ocular fluid current driven by intraocular pressure (IOP) as well as unfavorable drug disposition exerted by drug transporters before the drug reach retina. It is imperative to understand these processes and quantitate their influence for efficient designing of a sustained formulation or device to achieve efficient transscleral drug delivery. The current study was focused on the effects of intraocular pressure (IOP) and choroidal circulation on transscleral drug delivery using triamcinolone acetonide (TA) as a model drug. Rabbit eye IOP was modulated through cannulation in ex vivo study or through cryopexy of ciliary body in vivo studies before subtenon TA injection or episcleral TA-film implantation. In a subgroup of the rabbit eyes, localized choroid atrophy was induced by cryopexy before TA-film implantation. Each condition had a concurrent control group. The vitreous TA concentration was quantitated by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS/MS). The vitreous TA concentration was compared between the study and control groups for effect of IOP or choroid circulation. For ex vivo studies, higher IOP was a significant effect against TA penetration from episclera towards vitreous. TA was 8.5±5ng/mL in receptor chamber with a cross pressure of 50mmHg versus 15.9±10ng/mL with the cross pressure of 5mmHg; p=0.001, t-test. A multivariate regression demonstrated each mmHg of IOP increase would result in 3ng/mL lower concentration in the receptor chamber. Similar IOP effect was also identified in a 3-hour study using euthanized rabbit eyes whose IOP was controlled at 10 or 40mmHg by cannulation (3261±1821ng/mL vs. 755±763ng/mL; p=0.013, Wilcoxon test). However, the effect of IOP was not significant in alive animal with the same IOP setting. In vivo chronic study using low IOP (7.7mmHg) versus normal IOP (14.4mmHg), vitreous TA was not statistically significant (154±200ng/mL vs. 80±130ng/mL, p=0.17, Wilcoxon test). However, removing of choroidal circulation by local cryopexy significantly enhanced the TA penetration from episclera to vitreous (mean 163±129.8ng/mL for choroidal cryopexy vs. 81.8±37.2ng/mL for ciliary cryopexy or 75.5±36ng/mL for control group, p=0.007, regression analysis). In conclusion, the effect of IOP on transscleral drug delivery was not a significant effect in alive rabbit eyes; however, choroidal circulation seems to be a significant effect to affect TA penetration from episclera towards retina and vitreous.

The effect of ocular pigmentation on transscleral delivery of triamcinolone acetonide.

To determine the capacity and kinetics of the binding between triamcinolone acetonide (TA) and the ocular pigment for a better understanding of the transscleral delivery. In the in vitro study, natural melanin (sepia officinalis, Sigma-Aldrich) was incubated at 37°C with different concentrations of TA and the binding capacity/binding affinity was measured. The TA releasing profile from the melanin was also studied through repeated incubation of TA-melanin in fresh phosphate-buffed saline. In the ex vivo study, the effect of the choroidal pigment on the trans sclera/choroid permeability of TA was investigated through Franz-type vertical diffusion cells using both a TA suspension and a saturated TA solution. The amount of TA bound to melanin increases with the increase of the TA concentration and with an increase in the incubation time. A Scatchard analysis revealed that the maximum number of moles of TA bound to melanin is predicted to be 22.43 nmol/mg, with a binding affinity of K=2.4×10(-5) nM(-1). TA released from a pigment showed a fast phase within the first 24 h and a slow phase thereafter. About 40% of the bound TA released in the first day and 73.94% of accumulative release was observed after 5 days. The TA suspension showed more TA penetration through the scleral-choroid complex than the saturated solution (P=0.0104). The apparent permeability coefficients for the suspension across the sclera-choroid of pigmented and albino rabbits are 7.48±1.53×10(-6) cm/s and 10.78±2.49×10(-6) cm/s, respectively. TA can bind to and release from the ocular pigment, which may extend the TA ocular half-life and therapeutic duration when TA is delivered through a subtenon injection. A further in vivo study is warranted to validate the findings and to quantitate the magnitude of the difference between pigmented and albino animals.

Topical Bioavailability of Triamcinolone Acetonide: Effect of Occlusion

Background/Aims: Occlusion by covering the skin with an impermeable wrap enhances skin hydration, affects drug absorption and can induce the formation of a drug reservoir within the stratum corneum. This is desired in local therapy with topical corticosteroids. The aim of the study was to investigate the effect of occlusion before (experiment 1) and after (experiment 2) application on the penetration of triamcinolone acetonide (TACA) into the stratum corneum. Methods: The experiments were conducted on the forearms of 10 healthy volunteers. In experiment 1, 100 µg/cm² TACA in acetone were applied on 3 sites per arm, one arm having been pre-occluded for 16 h. In experiment 2, the same dose was applied on 2 sites per arm, and one arm was occluded after application until skin sampling. Stratum corneum samples were removed by tape stripping at 0.5, 4 and 24 h (experiment 1) and 4 and 24 h (experiment 2) after application. Corneocytes and TACA were quantified by ultraviolet-visible spectroscopy and HPLC, respectively. The total TACA amount penetrated into the stratum corneum was evaluated by multifactor ANOVA. Results: TACA penetration into the stratum corneum with and without pre-occlusion (experiment 1) showed no significant difference and decreased with time. Occlusion after application (experiment 2) produced a marked TACA accumulation within the stratum corneum, which persisted for 24 h. Conclusion: Pre-occlusion showed no effect on the topical bioavailability of TACA in the stratum corneum. In contrast, post-occlusion enhanced the TACA penetration by a factor of 2, favouring the development of a drug reservoir.

Topical bioavailability of triamcinolone acetonide: effect of dose and application frequency

The application frequency of topical corticosteroids is a recurrently debated topic. Multiple-daily applications are common, although a superior efficacy compared to once-daily application is not unequivocally proven. Only few pharmacokinetic studies investigating application frequency exist. The aim of the study was to investigate the effect of dose (Experiment 1) and application frequency (Experiment 2) on the penetration of triamcinolone acetonide (TACA) into human stratum corneum (SC) in vivo. The experiments were conducted on the forearms of 15 healthy volunteers. In Experiment 1, single TACA doses (300 microg/cm(2) and 100 microg/cm(2)) dissolved in acetone were applied on three sites per arm. In experiment 2, single (1 x 300 microg/cm(2)) and multiple (3 x 100 microg/cm(2)) TACA doses were similarly applied. SC samples were harvested by tape stripping after 0.5, 4 and 24 h (Experiment 1) and after 4, 8 and 24 h (Experiment 2). Corneocytes and TACA were quantified by UV/VIS spectroscopy and HPLC, respectively. TACA amounts penetrated into SC were statistically evaluated by a paired-sample t-test. In Experiment 1, TACA amounts within SC after application of 1 x 300 microg/cm(2) compared to 1 x 100 microg/cm(2) were only significantly different directly after application and similar at 4 and 24 h. In Experiment 2, multiple applications of 3 x 100 microg/cm(2) yielded higher TACA amounts compared to a single application of 1 x 300 microg/cm(2) at 4 and 8 h. At 24 h, no difference was observed. In conclusion, using this simple vehicle, considerable TACA amounts were retained within SC independently of dose and application frequency. A low TACA dose applied once should be preferred to a high dose, which may promote higher systemic exposure.

Delivery of triamcinolone acetonide through human epidermis: Effect of actiderm, a new hydrocolloid dermatological patch

The penetration of triamcinolone acetonide (TACA) through human epidermis following the evaporation of a finite dose of a hydroalcoholic tincture correlates positively with the applied volume and the penetrated amount of ethanol. The incorporation of salicylic acid into such a tincture extends the lag time and linear region of the TACA penetration curve. Covering with Actiderm following evaporation of a hydroalcoholic vehicle increases 2–3-fold the TACA flux with respect to uncovered skin or to occlusion with Saran Wrap. Solubility and partition coefficient determinations indicate similar thermodynamic activities for the drug in the three tinctures tested; however, diffusion experiments under in vivo mimic conditions show a higher TACA flux for the vehicle composed of isopropyl palmitate and ethanol. This phenomenon probably arises from different kinetics of the diffusion process in circumstances mimicking the in vivo conditions where vehicle components evaporate.