scholarly journals In Situ Gel Incorporating Disulfiram Nanoparticles Rescues the Retinal Dysfunction via ATP Collapse in Otsuka Long–Evans Tokushima Fatty Rats

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2171
Author(s):  
Saori Deguchi ◽  
Fumihiko Ogata ◽  
Mizuki Yamaguchi ◽  
Misa Minami ◽  
Hiroko Otake ◽  
...  
Keyword(s):  
Therapeutic Approaches ◽  
In Situ Gel ◽  
Retinal Dysfunction ◽  
Atp Production ◽  
Oletf Rats ◽  
Bead Mill ◽  
Long Evans ◽  
The Right ◽  
In Situ Gelling

We attempted to design an ophthalmic in situ gel formulation incorporating disulfiram (DIS) nanoparticles (Dis-NPs/ISG) and demonstrated the therapeutic effect of Dis-NPs/ISG on retinal dysfunction in 15-month-old Otsuka Long–Evans Tokushima Fatty (OLETF) rats, a rat model of diabetes. The DIS particles were crushed using a bead mill to prepare the nanoparticles, and the Dis-NPs/ISG was prepared using a combination of the DIS nanoparticles and an in situ gelling system based on methylcellulose (MC). The particle size of the Dis-NPs/ISG was 80–250 nm, and there was no detectable precipitation or aggregation for 1 month. Moreover, the Dis-NPs/ISG was gelled at 37 °C, and the drug was delivered into the retina by instillation. Only diethyldithiocarbamate (DDC) was detected in the retina (DIS was not detected) when the Dis-NPs/ISG was instilled in the right eye, and the DDC levels in the right retina were significantly higher than those in the left retina. In addition, the retinal residence time of the drug was prolonged by the application of the in situ gelling system, since the DDC levels in the retinas of rats instilled with Dis-NPs/ISG were higher than those in DIS nanoparticles without MC. Furthermore, repetitive instillation of the Dis-NPs/ISG attenuated the deterioration of electroretinograms (ERGs) in 15-month-old OLETF rats by preventing the collapse of ATP production via excessive nitric oxide and recovered the decrease in retinal function. These findings provide important information for the development of novel therapeutic approaches to diabetic retinopathy.

DEVELOPMENT AND INVESTIGATION OF TIMOLOL MALEATE AND TRAVOPROST COMBINATION NIOSOMAL IN SITU GELLING SYSTEM FOR THE TREATMENT OF GLAUCOMA

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (07) ◽  
pp. 33-35
Author(s):  
A Dubey ◽  
◽  
P Prabhu ◽  
N Nair ◽  
K Beladiya ◽  
...  
Keyword(s):  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Timolol Maleate ◽  
In Situ Gel ◽  
Vesicle Size ◽  
Gelling Time ◽  
In Situ Gelling ◽  
Vitro Release

The aim of the present investigation was to develop a combination of timolol maleate and travoprost niosomal in situ gelling system for the treatment of glaucoma. Niosomes were prepared by thin film hydration technique using rotary flash evaporator. A 32 factorial design was utilized to study the effect of the molar ratio of Span 60 (X1) and cholesterol (X2) on vesicle size, drug entrapment efficiency and in vitro release study. On the basis of vesicle size, maximum entrapment efficiency and in vitro release of drug, best formulations were selected for the preparation of niosomal in situ gel (Drop). On the basis of gelling time and viscosity, optimized ratio of the polymers was selected for the desired preparation. Selected niosomal batches were dispersed in carbopol 940 and HPMC K4M polymer solution (combination IF6) to form in situ gel niosomal formulations (Drop). The gelling time of the niosomal in situ gel (NIF1) was found to be the best (+++) and the viscosity was found to be 1190 cP. Zeta potential, average size analysis, polydispersibility index value was found to be -45.1 mV, 256.5 nm, 0.228 respectively. In vitro drug release was found to be within the range of 50.23 ± 0.54 to 60.23 ± 0.33% over the period of 6 h. IOP lowering activity of best formulation (NIF1) showed more significant and sustained effect than the marketed eye drops. Best formulation (NIF1) was found to be stable, sterile, non irritant and isotonic. Hence niosomal in situ gelling combination system may have the potential of bringing better application than the conventional ocular therapy with improved ocular bioavailability and increased patient compliance.

scholarly journals Ocular in situ gel: An overview

2019 ◽  
Vol 9 (1) ◽  
pp. 337-347 ◽  
Author(s):  
Asmat Majeed ◽  
Nisar Ahmad Khan
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Ocular Drug Delivery ◽  
The Body ◽  
Drug Bioavailability ◽  
In Situ Gel ◽  
In Situ Gelling ◽  
Gel System

Eye is the most sensitive organ of the body. Designing of ocular drug delivery system is the  most challenging field for pharmaceutical scientists as less than 5% of administered drug enters the eye due to the complicated anatomical structure of the eye, small absorptive surface and low transparency of the cornea, lipophilicity of corneal epithelium, pre corneal loss (due to nasolacrimal drainage), bonding of the drug with proteins contained in tear fluid, blinking, low capacity of conjunctival sac, that restricts the entry of drug molecule at the site of action and ultimately leads to poor ocular therapy. To improve ophthalmic drug bioavailability, there are considerable efforts directed towards newer drug delivery systems for ophthalmic administration. These novel drug delivery systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. A lot of research going on in this area proves the fact that in situ gelling systems can be beneficial in the ocular drug delivery. In situ gel forming systems are drug delivery systems that are in solution form before administration in the body but once administered, undergo  in situ gelation, to form a gel triggered by external stimulus such as temperature, pH etc.  This review is to Specify a brief summary about in situ gels, various approaches for in situ gelling systems, different types of polymers used in in situ gels, their mechanisms of gel formation and evaluation of polymeric in situ gel. Keywords: in situ gel, polymers, Temperature induced in situ gel system, pH induced in situ gel system, Ion activated systems.

scholarly journals Nasal In Situ Gel: Novel Approach for Nasal Drug Delivery

2020 ◽  
Vol 10 (2-s) ◽  
pp. 183-197
Author(s):  
Anjali Sunil Sabale ◽  
Abhijeet D Kulkarni ◽  
Ajay Sunil Sabale
Keyword(s):  
Drug Delivery ◽  
Patient Compliance ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Nasal Drug Delivery ◽  
In Situ Gel ◽  
Reduced Frequency ◽  
Conventional Drug ◽  
In Situ Gelling

Nasal delivery is an alternative to oral or parenteral administration due to certain limitations such as absorption of the drug, drug targeting to particular organs can cause a problem for administration through oral route.  The nasal route has also been successfully used for bypassing the blood-brain barrier and afterword delivering drug molecules to the central nervous system. Also, lag time related to oral drug delivery is reduces by this route and offers noninvasiveness, self-medication, patient comfort, and patient compliance. Extend drug delivery can be attained by different new dosage forms like in situ gel. In situ formulations are drug delivery systems. The in-situ gelling system is a process in which the solution forms of a gel before administration in the body, but once administrated, it undergoes gelation in-situ, to form a gel. In situ gelling system becomes very popular nowadays because of their several advantages over conventional drug delivery systems like a sustained and prolonged release of a drug, reduced Frequency of administration, improved patient compliance and comfort. Approaches towards the various formulation of in-situ gel concerning temperature, pH, and physicochemical conditions. The in situ gel-forming polymeric formulations offer several advantages like sustained and prolonged action reduced Frequency of administration, in comparison to conventional drug delivery systems.  From a manufacturing point of view, the production of such systems is less complex and thus lowers the investment and manufacturing cost. Various evaluation parameters are considered during the preparation of In-Situ gel. Keywords: Nasal Drug Delivery, In Situ gel, gelation, polymers, etc

scholarly journals A Recent Overview: In Situ Gel Smart Carriers for Ocular Drug Delivery

2021 ◽  
Vol 11 (6-S) ◽  
pp. 195-205
Author(s):  
Mandeep Singh ◽  
Dhruv Dev ◽  
D.N. Prasad
Keyword(s):  
Drug Delivery ◽  
Delivery Systems ◽  
Eye Drops ◽  
Adhesive Properties ◽  
In Situ Gel ◽  
Temperature Changes ◽  
Polymeric Systems ◽  
Protective Layers ◽  
In Situ Gelling

Delivery of the drug to the ocular area is blocked by the protective layers covering the eyes; it has always been a major problem to find effective bioavailability of the active drug in the ocular area due to the short duration of precorneal majority ocular stay. Direct delivery systems combine as well as oil, solution, and suspension, as a result, many delivery systems are not able to effectively treat eye diseases. Many works have been done and are being done to overcome this problem one of which is to use in-situ to build polymeric systems. Ocular In-situ gelling systems are a new class of eye drug delivery systems that are initially in solution but are quickly transformed into a viscous gel when introduced or inserted into an ocular cavity where active drugs are released continuously. This sol-to-gel phase conversion depends on a variety of factors such as changes in pH, ion presence, and temperature changes. Post-transplanting gel selects viscosity and bio-adhesive properties, which prolongs the gel's stay in the ocular area and also releases the drug in a long and continuous way unlike conventional eye drops and ointments. This review is a brief overview of situ gels, the various methods of in situ gelling systems, the different types of polymers used in situ gels, their gel-based methods, and the polymeric testing of situ gel. Keywords: In-situ gel, Polymers, and ion triggered in-situ gel, Mechanism, Evaluation parameters

Nasal In-situ Gel: An Approach to Enhance Therapeutic Benefits of the Drug

2020 ◽  
Vol 10 (2) ◽  
pp. 85-95
Author(s):  
Kapil Khatri ◽  
Shikha Jain ◽  
Satish Shilpi
Keyword(s):  
Drug Delivery ◽  
Physicochemical Characterization ◽  
Systemic Circulation ◽  
Nasal Administration ◽  
Nasal Drug Delivery ◽  
In Situ Gel ◽  
Therapeutic Benefits ◽  
The Central Nervous System ◽  
In Situ Gelling

Objective:: Drug delivery through the nasal route is emerging as a promising approach due to its capability to transport the drug to the systemic circulation and the central nervous system for therapeutic benefits. Methods: In-situ gelling formulations comprising polymeric substances are emerging as preferential nasal drug delivery systems. When exposed to biological stimuli, they have the ability to undergo a solgel conversion. Result: Such mucoadhesive in-situ gel formulations designed and developed for the nasal administration have the ability to prolong the residence time of formulation in the nasal cavity, thereby serving better for complete uptake of the drug across the nasal mucosa. Conclusion: Thus, this review focuses on temperature-responsive, pH-responsive and ion responsive polymers utilized in the nasal in-situ gels together with their physicochemical characterization, evaluation and pharmaceutical applications.

Floating In Situ Gel based on Alginate as Carrier for Stomach-Specific Drug Delivery of Famotidine

2010 ◽  
Vol 3 (3) ◽  
pp. 1092-1104 ◽  
Author(s):  
Jayvadan K. Patel Patel ◽  
Jayant R. Chavda ◽  
Moin K Modasiya
Keyword(s):  
Drug Release ◽  
Sodium Alginate ◽  
Calcium Chloride ◽  
Sodium Citrate ◽  
Sustained Drug Release ◽  
In Situ Gel ◽  
In Vivo Testing ◽  
In Situ Gelling

Alginate based floating in situ gelling systems of famotidine (FIGF) were prepared by dissolving varying concentrations of alginate in deionized water containing sodium citrate, to which varying concentrations of drug and calcium chloride was added and dissolved by stirring. Results of preliminary trials indicate that concentrations of sodium alginate, calcium chloride and sodium citrate affected the characteristics of in situ gel. A 32 full factorial design was employed to study the effect of independent variables, concentration of sodium alginate (X1) and concentration of calcium chloride (X2) on dependent variables, i.e. viscosity, drug content, drug release at 4 hrs (Q50) and drug release at 8 hrs (Q80). A sustained drug release was obtained for more than 8 hrs. In vivo testing of FIGF to albino Wistar rats demonstrated significant anti-ulcer effect of famotidine.

scholarly journals Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type II diabetic rats

2004 ◽  
Vol 183 (1) ◽  
pp. 183-194 ◽  
Author(s):  
Dae Ryong Cha ◽  
Young Sun Kang ◽  
Sang Youb Han ◽  
Yi Hwa Jee ◽  
Kum Hyun Han ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Immunohistochemical Staining ◽  
Early Stage ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Oletf Rats ◽  
Long Evans ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression

Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetic nephropathy. We investigated serial changes of VEGF in the kidney and assessed whether glomerular and urinary VEGF levels are related to the severity of diabetic nephropathy. Furthermore, we examined the relationship between urinary VEGF levels and the urinary albumin excretion (UAE) rate in Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats. Glomerular VEGF mRNA expression and protein synthesis were evaluated by the reverse transcription-polymerase chain reaction, immunohistochemical staining and in situ hybridization. Urinary levels of VEGF were determined by enzyme-linked immunosorbent assay. UAE was significantly higher in OLETF rats than in control Long-Evans-Tokushima-Fatty (LETO) rats throughout the study period. Urinary VEGF levels were significantly higher from 25 to 37 weeks, and then gradually reduced until 55 weeks, although the levels were still higher than those in control rats. Urinary VEGF levels also showed a significant positive correlation with UAE (r=0.262, P=0.045) and serum creatinine (r=0.398, P=0.044), and were found to be independently correlated with UAE by Spearman’s rank correlation. By immunohistochemical staining and in situ hybridization, VEGF was mainly detected in the podocytes in the glomeruli. Interestingly, a significant increase in VEGF mRNA expression was observed in the early period of diabetic nephropathy, and this was associated with increased urinary VEGF excretion. Thus, the overproduction of VEGF in the diabetic kidney may participate in the pathogenesis of early-stage diabetic nephropathy.

scholarly journals In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals

2020 ◽  
Vol 21 (19) ◽  
pp. 7083
Author(s):  
Noriaki Nagai ◽  
Takumi Isaka ◽  
Saori Deguchi ◽  
Misa Minami ◽  
Mizuki Yamaguchi ◽  
...  
Keyword(s):  
Pluronic F127 ◽  
Significant Information ◽  
Corneal Permeability ◽  
Enhanced Absorption ◽  
Bead Mill ◽  
Resident Time ◽  
Energy Dependent ◽  
Corneal Permeation ◽  
In Situ Gelling

We previously designed an ophthalmic dispersion containing indomethacin nanocrystals (IMC-NCs), showing that multiple energy-dependent endocytoses led to the enhanced absorption of drugs from ocular dosage forms. In this study, we attempted to prepare Pluronic F-127 (PLF-127)-based in situ gel (ISG) incorporating IMC-NCs, and we investigated whether the instillation of the newly developed ISG incorporating IMC-NCs prolonged the precorneal resident time of the drug and improved ocular bioavailability. The IMC-NC-incorporating ISG was prepared using the bead-mill method and PLF-127, which yielded a mean particle size of 50–150 nm. The viscosity of the IMC-NC-incorporating ISG was higher at 37 °C than at 10 °C, and the diffusion and release of IMC-NCs in the IMC-NC-incorporating ISG were decreased by PLF-127 at 37 °C. In experiments using rabbits, the retention time of IMC levels in the lacrimal fluid was enhanced with PLF-127 in the IMC-NC-incorporating ISG, whereby the IMC-NC-incorporating ISG with 5% and 10% PLF-127 increased the transcorneal penetration of the IMCs. In contrast to the results with optimal PLF-127 (5% and 10%), excessive PLF-127 (15%) decreased the uptake of IMC-NCs after instillation. In conclusion, we found that IMC-NC-incorporating ISG with an optimal amount of PLF-127 (5–10%) resulted in higher IMC corneal permeation after instillation than that with excessive PLF-127, probably because of the balance between higher residence time and faster diffusion of IMC-NCs on the ocular surface. These findings provide significant information for developing ophthalmic nanomedicines.

Development of Thymol microsponges loaded In situ gel for the treatment of Periodontitis

2020 ◽  
Vol 17 ◽  
Author(s):  
Vinita C. Patole ◽  
Shilpa P. Chaudhari
Keyword(s):  
Antimicrobial Activity ◽  
Alveolar Bone ◽  
In Vitro Release ◽  
Bone Destruction ◽  
Fractional Factorial ◽  
Oral Disease ◽  
Tartrate Resistant Acid Phosphatase ◽  
In Situ Gel ◽  
In Situ Gelling

Objective: Periodontitis is an oral disease categorized by disturbance of periodontal tissue and creation of periodontal pockets. Thymol (TH) loaded microsponge in situ gelling system was formulated for local action in the periodontal cavity for the management of periodontitis. Method: Solvent evaporation technique was utilized for preparation of microsponges. A Fractional factorial design (FFD) was used to screen the high risk variables impacting the characteristics of the (TH) microsponges and further optimized using Box-Behnken design. The optimized microsponges were then characterized by DSC, SEM, antimicrobial activity, in– vitro release and then incorporated in the in situ gelling system. Ligature model was used to induce periodontitis in Sprague Dawley rats. Results: The microsponges showed good characteristics such as particle size, entrapment efficiency and mucoadhesiveness 45 µm, 92.99±0.2%, 96±0.26% respectively. SEM revealed the spherical morphology of the microsponges with sustained release of TH for 10h and antimicrobial activity against S.mutans and C.albicans. Treatment with thymol loaded in situ gel (THLMG) showed decrease in gingival inflammation and tooth mobility as well as in serum biochemical parameters like serum C-reactive proteins, leucocyte count, alkaline phosphatase and tartrate-resistant acid phosphatase when compared to disease group. The histopathological study of the periodontium confirmed significant reduction of inflammation and alveolar bone destruction (p<0.05) in rats. Conclusion: Thus THLMG decreased infiltration of inflammatory cells and prevented osteoclatogenesis and osteoblast apoptosis which further favored decrease in inflammation and alveolar bone loss in periodontitis. Thus THLMG could be a better alternative to synthetic antimicrobials and antibiotics to treat periodontitis.

Sustained ophthalmic delivery of pH triggered Cromolyn sodium in situ gel

2021 ◽  
pp. 6211-6215
Author(s):  
S. Subramanian ◽  
B. Prasanth
Keyword(s):  
Drug Release ◽  
Cromolyn Sodium ◽  
Fickian Diffusion ◽  
Molar Ratio ◽  
Eye Drops ◽  
In Vitro Drug Release ◽  
In Situ Gel ◽  
In Situ Gelling

The research study intends to formulate pH triggered in situ gel of Cromolyn sodium composed of Polyacrylic acid (carbopol 934) polymer in combination with Hydroxypropyl Methylcellulose (HPMC K4M) polymer at 1:1, 1.5:1, 2:1 molar ratio by utilizing pH trigger method. Formulations were evaluated for pH, viscosity, gelling capacity, drug content and in vitro drug release. Results of Carbopol 934 and HPMC K4M based in situ gelling systems at 1:1, 1.5:1, 2:1 shown that the formulations were fluid state at room temperature in a formulated pH (pH 4.5) and went through fast progress into the viscous gel phase at the pH of the tear fluid 7.4. The viscosity of formulated pH triggered in situ gel at 2:1 molar ratio shown excellent result compares to 1:1, 1.5:1 molar ratio. The in vitro drug release of the developed in situ gelling formulations at 1:1, 1.5:1, 2:1 molar ratios increases the contact time and showed a non – fickian diffusion type of release behavior with 94.45%, 83.26%, 70.48% respectively over 8 hours periods compared with that of marketed formulation that shows 99.4% over 4 hours. Thus, the developed system at 2:1 molar ratio acts as a viable alternative to conventional eye drops and also prevent the rapid drainage.

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