scholarly journals Comparative study on pharmacokinetics and toxicity of intravitreal and sub-Tenon injection of triamcinolone acetonide in ocular tissues

2020 ◽  
Vol 13 (12) ◽  
pp. 1864-1871
Author(s):  
Yuko Arie ◽  
Ayako Suzuki ◽  
Takeshi Okabe ◽  
Mitsuyo Takashima ◽  
Mayumi Takata ◽  
...  
Keyword(s):  
Triamcinolone Acetonide ◽  
Aqueous Humor ◽  
Species Difference ◽  
Clinical Signs ◽  
Vitreous Body ◽  
Systemic Circulation ◽  
Ocular Tissues ◽  
Optical Discharge ◽  
Ocular Symptoms ◽  
Injection Methods

AIM: To compare the differences in kinetics, distribution, and toxicity of triamcinolone acetonide (TA) between the injection methods, sub-Tenon and intravitreal injections in rabbit ocular tissues. METHODS: TA was injected into the vitreous or the sub-Tenon in rabbits. For pharmacokinetic study, rabbits were sacrificed periodically and then TA in blood and ocular tissues (retina/choroids, vitreous, and aqueous humor) were measured over 91d. For toxicological study, clinical signs, slit-lamp microscopic examination, ophthalmological test were performed. The eyeballs and surrounding tissues were collected and fixed with glutaraldehyde-formalin solution, and then paraffin embedded for histological investigation. RESULTS: Higher levels of TA were distributed in the intraocular tissues when injected into the vitreous compared to the sub-Tenon. Conversely, TA level was remarkably lower in the rabbits which received intravitreal TA injections than those treated with sub-Tenon injection throughout the study period in plasma. Optical discharge probably caused by systemic circulation of TA was observed by receiving sub-Tenon TA injection. Meanwhile, technic-associated toxicological ocular symptoms and findings were more frequently observed in intravitreal injection than in sub-Tenon injection. CONCLUSION: There are significant differences in kinetics and distribution of TA in vitreous body, aqueous humor and plasma, between the two injection methods. Although further study is needed to explain the species difference between human and rabbit, it is assumed that the difference in the frequency of intraocular pressure elevation and cataract formation by TA between the two injection methods are directly related to the TA concentrations in aqueous humor and vitreous body in each injection methods. Systemic toxicity and technic-associated toxicity are also closely related to kinetics of TA in plasma and each injection method itself, respectively.

scholarly journals Melt-Cast Films Significantly Enhance Triamcinolone Acetonide Delivery to the Deeper Ocular Tissues

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 158
Author(s):  
Akshaya Tatke ◽  
Narendar Dudhipala ◽  
Karthik Janga ◽  
Bhavik Soneta ◽  
Bharathi Avula ◽  
...  
Keyword(s):  
Triamcinolone Acetonide ◽  
Polymer Matrix ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Invasive Technique ◽  
Content Uniformity ◽  
Scanning Calorimetry ◽  
Ocular Tissues

Delivering an effective drug load to the posterior section of the ocular tissues, while using a non-invasive technique, has always been a challenge. In this regard, the goal of the present study was to develop sustained release triamcinolone acetonide (TA) loaded polymeric matrix films for ocular delivery. The TA-films were prepared in two different polymer matrices, with drug loadings of 10% and 20% w/w, and they were evaluated for ocular distribution in vivo in a conscious rabbit model. A 4% w/v TA suspension (TA-C) was used as a control for in vitro and in vivo studies. The TA-films, prepared with melt-cast technology, used polyethylene oxide (PEO) and Soluplus® as the polymer matrix. The films were evaluated with respect to assay, content uniformity, excipient interaction, and permeability across isolated rabbit sclera. The distribution of TA in the ocular tissues, post topical administration, was determined in New Zealand male albino rabbits as a function of dose, and was compared against TA-C. The assay of the 10% and 20% w/w film was in the range from 70–79% and 92–94% for the Soluplus® and PEO films, respectively, and content uniformity was in the range of 95–103% for both the films. The assay of the TA from Soluplus® films was less compared with the PEO films and showed an interaction with TA, as revealed by Differential Scanning Calorimetry (DSC). Hence, Soluplus® films were not selected for further studies. No interaction was observed between the drug and PEO polymer matrix. The enhancement of trans-scleral flux and permeability of TA was about 1.16 and 1.33-folds, respectively, from the 10% w/w PEO and 3.5 and 2.12-folds, respectively, from the 20% w/w PEO films, as compared with TA-C formulations. The in vivo studies demonstrate that significantly higher TA levels were observed in the anterior and posterior segments of the eye at the end of 6h with the PEO films. Therefore, the PEO based polymeric films were able to deliver TA into the back of the eye efficiently and for prolonged periods.

scholarly journals Morphological Changes in the Bone Marrow of the Dogs with Visceral Leishmaniasis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Claudia Momo ◽  
Ana Paula Prudente Jacintho ◽  
Pamela Rodrigues Reina Moreira ◽  
Danísio Prado Munari ◽  
Gisele Fabrino Machado ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Morphological Changes ◽  
Clinical Signs ◽  
Parasite Load ◽  
Systemic Circulation ◽  
Clinical Group ◽  
Leishmania Chagasi ◽  
Control Center ◽  
A Site

The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected byLeishmania (Leishmania) chagasi.Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL), were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eosin. The lesion intensity was classified as mild, moderate, or severe. The parasite load was determined using immunohistochemistry. The most important lesions consisted of multifocal to diffuse granulomas, megakaryocytic dysplasia, and medullary aplasia. There were no statistical differences between the three clinical groups regarding parasite load and lesion intensity. Asymptomatic dogs also presented high parasitism in the bone marrow as dogs with clinical signs of VL. It was concluded that, regardless of clinical group, the bone marrow is a site for multiplication ofLeishmania chagasi. Possibly, the bone marrow dysplasia may arise from the presence of many parasitized and activated macrophages in this organ. Consequently, it affects the profile of hematopoietic cells in the bone marrow and systemic circulation.

scholarly journals In Situ Gel of Triamcinolone Acetonide-Loaded Solid Lipid Nanoparticles for Improved Topical Ocular Delivery: Tear Kinetics and Ocular Disposition Studies

Nanomaterials ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 33 ◽  
Author(s):  
Akshaya Tatke ◽  
Narendar Dudhipala ◽  
Karthik Janga ◽  
Sai Balguri ◽  
Bharathi Avula ◽  
...  
Keyword(s):  
Rheological Properties ◽  
Triamcinolone Acetonide ◽  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
Gellan Gum ◽  
Ocular Tissues ◽  
In Situ Gel ◽  
Solid Lipid ◽  
Transcorneal Permeability

Triamcinolone acetonide (TA), an intermediate acting corticosteroid, is used in the treatment of posterior ocular diseases, such as inflammation, posterior uveitis, and diabetic macular edema. The objective of this investigation was to prepare TA-loaded solid lipid nanoparticles (TA-SLNs) and in situ gel (TA-SLN-IG) formulations for delivery into the deeper ocular tissues through the topical route. TA-SLNs were prepared by hot homogenization and ultrasonication method using glyceryl monostearate and Compritol® 888ATO as solid lipids and Tween®80 and Pluronic® F-68 as surfactants. TA-SLNs were optimized and converted to TA-SLN-IG by the inclusion of gellan gum and evaluated for their rheological properties. In vitro transcorneal permeability and in vivo ocular distribution of the TA-SLNs and TA-SLN-IG were studied using isolated rabbit corneas and New Zealand albino rabbits, respectively, and compared with TA suspension, used as control (TA-C). Particle size, PDI, zeta potential, assay, and entrapment efficiency of TA-SLNs were in the range of 200–350 nm, 0.3–0.45, −52.31 to −64.35 mV, 70–98%, and 97–99%, respectively. TA-SLN-IG with 0.3% gellan gum exhibited better rheological properties. The transcorneal permeability of TA-SLN and TA-SLN-IG was 10.2 and 9.3-folds higher compared to TA-C. TA-SLN-IG showed maximum tear concentration at 2 h, indicating an improved pre-corneal residence time, as well as higher concentrations in aqueous humor, vitreous humor and cornea at 6 h, suggesting sustained delivery of the drug into the anterior and posterior segment ocular tissues, when compared to TA-SLN and TA-C. The results, therefore, demonstrate that the lipid based nanoparticulate system combined with the in situ gelling agents can be a promising drug delivery platform for the deeper ocular tissues.

scholarly journals Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 805
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Inflammatory Responses ◽  
Clinical Signs ◽  
Systemic Circulation ◽  
Cell Responses ◽  
Pituitary Adenylate Cyclase ◽  
Gastrointestinal Colonization ◽  
First Time

Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of C. jejuni-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae.

Diffusive Transport in the Vitreous Humor: Experimental and Analytical Studies

2019 ◽  
Vol 141 (5) ◽  
Author(s):  
Anita Penkova ◽  
Rex Moats ◽  
Mark S. Humayun ◽  
Scott Fraser ◽  
Satwindar Singh Sadhal
Keyword(s):  
Diffusion Coefficient ◽  
Drug Transport ◽  
Initial Conditions ◽  
Imaging Techniques ◽  
Vitreous Body ◽  
Vitreous Humor ◽  
Ocular Tissues ◽  
Intravitreal Drug Delivery ◽  
Magnetic Resonance Imaging Mri ◽  
Diffusive Movement

In relation to intravitreal drug delivery, predictive mathematical models for drug transport are being developed, and to effectively implement these for retinal delivery, the information on biophysical properties of various ocular tissues is fundamentally important. It is therefore necessary to accurately measure the diffusion coefficient of drugs and drug surrogates in the vitreous humor. In this review, we present the studies conducted by various researchers on such measurements over the last several decades. These include imaging techniques (fluorescence and magnetic resonance imaging (MRI)) that make use of introducing a contrast agent or a labeled drug into the vitreous and tracking its diffusive movement at various time points. A predictive model for the same initial conditions when matched with the experimental measurements provides the diffusion coefficient, leading to results for various molecules ranging in size from approximately 0.1 to 160 kDa. For real drugs, the effectiveness of this system depends on the successful labeling of the drugs with suitable contrast agents such as fluorescein and gadolinium or manganese so that fluorescence or MR imagining could be conducted. Besides this technique, some work has been carried out using the diffusion apparatus for measuring permeation of a drug across an excised vitreous body from a donor chamber to the receptor by sampling assays from the chambers at various time intervals. This has the advantage of not requiring labeling but is otherwise more disruptive to the vitreous. Some success with nanoparticles has been achieved using dynamic light scattering (DLS), and presently, radioactive labeling is being explored.

scholarly journals Cytomegalovirus Uveitis with Hypopyon Mimicking Bacterial Endophthalmitis

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Atsushi Yoshida ◽  
Hiroto Obata ◽  
Hidetoshi Kawashima
Keyword(s):  
Anterior Chamber ◽  
Aqueous Humor ◽  
Vitreous Body ◽  
Corneal Endothelial Cell ◽  
Bacterial Endophthalmitis ◽  
Fungus Culture ◽  
Corrected Visual Acuity ◽  
One Year ◽  
Systemic Infections ◽  
Measurable Range

We report an 83-year-old immune-competent female with unilateral endophthalmitis extraordinarily caused by cytomegalovirus (CMV). Since she was suspected of suffering possible bacterial endophthalmitis, she was referred to our hospital. At the first visit, hypopyon in the anterior chamber and the opacity of vitreous body were observed in the left eye. The best-corrected visual acuity (BCVA) of the left eye was counting fingers and the intraocular pressure (IOP) was 20 mmHg. Bacterial and fungus culture of the aqueous humor revealed no infection. However, the density of corneal endothelial cell was less than the measurable range and CMV was detected by PCR of the aqueous humor. She was immune-competent and the data indicated neither systemic infections nor diseases. Systemic valganciclovir and corticosteroid were administered. After that, hypopyon in the anterior chamber and the opacity of vitreous body of the left eye were improved, and the BCVA of the left eye was 20/200 one year after the first visit. However, the inflammation of the anterior chamber recurred accompanied by elevated IOP after the discontinuance of administering valganciclovir. CMV-induced uveitis accompanied with hypopyon is quite rare. Therefore, it can be easily misdiagnosed as bacterial endophthalmitis.

Extravascular foci ofTrypanosoma vivaxin goats: the central nervous system and aqueous humor of the eye as potential sources of relapse infections after chemotherapy

Parasitology ◽  
1988 ◽  
Vol 97 (1) ◽  
pp. 51-61 ◽  
Author(s):  
D. D. Whitelaw ◽  
P. R. Gardiner ◽  
M. Murray
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Choroid Plexus ◽  
Aqueous Humor ◽  
Acute Infection ◽  
Clinical Signs ◽  
Central Nervous System Involvement ◽  
Severe Illness ◽  
Diminazene Aceturate ◽  
The Central Nervous System

SUMMARYRelapse of parasitaemia after drug treatment of trypanosome infections is normally attributed to drug-resistance on the part of the parasite, under-dosage of the drug or reinfection of the host. In addition, inaccessibility of parasites to drug through sequestration in privileged extravascular sites has been shown in the past to occur withTrypanosoma brucei, and we have obtained evidence that extravascular foci ofT. vivaxcan also serve as a source of relapsing infections. Infection of goats with a West African stock ofT. vivaxresulted in severe illness, which was fatal if untreated. During the terminal stage of an acute infection, clinical signs of central nervous system involvement were apparent. Histologically, the choroid plexus was swollen and oedematous, and in some cases meningitis or meningoencephalitis was seen. Trypanosomes could be detected in the cerebrospinal fluid, and also extravascularly in the choroid plexus and meninges. In three cases they were present in the aqueous humor, associated with corneal cloudiness or opacity. Treatment of 2 goats with the trypanocidal drug diminazene aceturate eliminated parasitaemia, but infections in both relapsed about 6 weeks later, despite trypanosomes being undetectable in the bloodstream during the intervening period. We conclude that the relapse infections were caused by re-emergence of trypanosomes from the CNS and/or the eye, where sequestered parasites may have been inaccessible to the trypanocide.

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