scholarly journals Sodium glycodeoxycholate and sodium deoxycholate as epithelial permeation enhancers: in vitro and ex vivo intestinal and buccal bioassays

2021 ◽  
Vol 159 ◽  
pp. 105737
Author(s):  
David J. Brayden ◽  
Vivien Stuettgen
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naresh Polisetti ◽  
Anke Schmid ◽  
Ursula Schlötzer-Schrehardt ◽  
Philip Maier ◽  
Stefan J. Lang ◽  
...  

AbstractAllogenic transplants of the cornea are prone to rejection, especially in repetitive transplantation and in scarred or highly vascularized recipient sites. Patients with these ailments would particularly benefit from the possibility to use non-immunogenic decellularized tissue scaffolds for transplantation, which may be repopulated by host cells in situ or in vitro. So, the aim of this study was to develop a fast and efficient decellularization method for creating a human corneal extracellular matrix scaffold suitable for repopulation with human cells from the corneal limbus. To decellularize human donor corneas, sodium deoxycholate, deoxyribonuclease I, and dextran were assessed to remove cells and nuclei and to control tissue swelling, respectively. We evaluated the decellularization effects on the ultrastructure, optical, mechanical, and biological properties of the human cornea. Scaffold recellularization was studied using primary human limbal epithelial cells, stromal cells, and melanocytes in vitro and a lamellar transplantation approach ex vivo. Our data strongly suggest that this approach allowed the effective removal of cellular and nuclear material in a very short period of time while preserving extracellular matrix proteins, glycosaminoglycans, tissue structure, and optical transmission properties. In vitro recellularization demonstrated good biocompatibility of the decellularized human cornea and ex vivo transplantation revealed complete epithelialization and stromal repopulation from the host tissue. Thus, the generated decellularized human corneal scaffold could be a promising biological material for anterior corneal reconstruction in the treatment of corneal defects.


2020 ◽  
Author(s):  
Naresh Polisetti ◽  
Anke Schmid ◽  
Ursula Schlötzer-Schrehardt ◽  
Philip Maier ◽  
Stefan Lang ◽  
...  

Abstract Allogenic transplants of the cornea are prone to rejection, especially in repetitive transplantation and in scarred or highly vascularized recipient sites. Patients with these ailments would particularly benefit from the possibility to use non-immunogenic decellularized tissue scaffolds for transplantation, which may be repopulated by host cells in situ or in vitro. So, the aim of this study was to develop a fast and efficient decellularization method for creating a human corneal extracellular matrix scaffold suitable for repopulation with human cells from the corneal limbus. To decellularize human donor corneas, sodium deoxycholate, deoxyribonuclease I, and dextran were assessed to remove cells and nuclei and to control tissue swelling, respectively. We evaluated the decellularization effects on the ultrastructure, optical, mechanical, and biological properties of the human cornea. Scaffold recellularization was studied using primary human limbal epithelial cells, stromal cells, and melanocytes in vitro and a lamellar transplantation approach ex vivo. Our data strongly suggest that this approach allowed the effective removal of cellular and nuclear material in a very short period of time while preserving extracellular matrix proteins, glycosaminoglycans, tissue structure, and optical transmission properties. In vitro recellularization demonstrated good biocompatibility of the decellularized human cornea and ex vivo transplantation revealed complete epithelialization and stromal repopulation from the host tissue. Thus, the generated decellularized human corneal scaffold could be a promising biological material for anterior corneal reconstruction in the treatment of corneal defects.


2012 ◽  
Vol 48 (2) ◽  
pp. 335-345 ◽  
Author(s):  
Appa Rao Potu ◽  
Naresh Pujari ◽  
Shashidher Burra ◽  
Prabhakar Reddy Veerareddy

The aim of present study was to develop and evaluate buccoadhesive Quetiapine Fumarate (QF) tablets, which is extensively metabolised by liver. Buccoadhesive tablets of QF were prepared using HPMC K4M, HPMC K15M and combination of carbopol and HPC as mucoadhesive polymers by direct compression method. Sodium deoxycholate was added to formulation to improve the permeation of drug. The formulations were tested for bioadhesion strength, ex vivo residence time, swelling time and in vitro dissolution studies and ex vivo permeation studies. Optimized formulation (F3) showed 92% in vitro release in 8 h and 67% permeation of drug through porcine buccal mucosa and followed fickian release mechanism with zero order kinetics. FTIR studies of optimized formulation showed no evidence of interaction between the drug and polymers. In vivo mucoadhesive behaviour of optimized formulation was performed and subjective parameters were evaluated.


Author(s):  
Vipulbhai Mandli ◽  
Shailesh T. Prajapati

The purpose of this research was to prepare and evaluate monolithic drug-in-adhesive type patches of Rasagiline Mesylate (RM) containing penetration enhancer and having seven day wear property. Preformulation studies like solubility in permeation enhancers, compatibility study, transmission study, uptake study and crystallization study of Rasagiline Mesylate in various pressure sensitive adhesive polymers were performed. Transdermal system was prepared by solvent casting method. The effects of various permeation enhancers (Propylene Glycol, Oleic Acid, Isopropyl Palmitate, and lauryl lactate) on the ex-vivo transcutaneous absorption of Rasagiline Mesylate through human cadaver skin were evaluated by modified Franz diffusion cell system. Ex-vivo transcutaneous absorption of prepared transdermal patch was performed using different concentration of Lauryl lactate (3%, 5%, and 7%). In-vitro Adhesion testing (Peel, tack shear etc.) was performed on different dry GSM (Grams per Square Meter) of patch like 80GSM, 100 GSM and 150 GSM. The final transdermal patches were tested for appearance, weight of matrix, thickness, % assay of drug content, in-vitro adhesion testing, cold flow study and ex-vivo skin permeation studies. Based on crystallization study and adhesion testing, Durotak-4098 (14% drug concentration) was selected as pressure sensitive adhesive. Patch containing Lauryl lactate showed highest cumulative permeation compared to other permeation enhancers. The patch containing 5% laurel lactate showed greater transdermal flux (2.36 µg/cm2 /hr). Patch with 150 dry GSM showing promising adhesion properties. Backing film Scotchpak 9723 and release liner Saint Gobain 8310 was selected based on transmission and uptake study of Rasagiline Mesylate. Stability study indicates that developed formulation remains stable. In conclusion, the present research confirms the practicability of developing Rasagiline Mesylate transdermal system.


2021 ◽  
Vol 22 (18) ◽  
pp. 10067
Author(s):  
Naresh Polisetti ◽  
Benjamin Roschinski ◽  
Ursula Schlötzer-Schrehardt ◽  
Philip Maier ◽  
Günther Schlunck ◽  
...  

The transplantation of ex vivo expanded limbal epithelial progenitor cells (LEPCs) on amniotic membrane or fibrin gel is an established therapeutic strategy to regenerate the damaged corneal surface in patients with limbal stem cell deficiency (LSCD), but the long-term success rate is restricted. A scaffold with niche-specific structure and extracellular matrix (ECM) composition might have the advantage to improve long-term clinical outcomes, in particular for patients with severe damage or complete loss of the limbal niche tissue structure. Therefore, we evaluated the decellularized human limbus (DHL) as a biomimetic scaffold for the transplantation of LEPCs. Corneoscleral tissue was decellularized by sodium deoxycholate and deoxyribonuclease I in the presence or absence of dextran. We evaluated the efficiency of decellularization and its effects on the ultrastructure and ECM composition of the human corneal limbus. The recellularization of these scaffolds was studied by plating cultured LEPCs and limbal melanocytes (LMs) or by allowing cells to migrate from the host tissue following a lamellar transplantation ex vivo. Our decellularization protocol rapidly and effectively removed cellular and nuclear material while preserving the native ECM composition. In vitro recellularization by LEPCs and LMs demonstrated the good biocompatibility of the DHL and intrastromal invasion of LEPCs. Ex vivo transplantation of DHL revealed complete epithelialization as well as melanocytic and stromal repopulation from the host tissue. Thus, the generated DHL scaffold could be a promising biological material as a carrier for the transplantation of LEPCs to treat LSCD.


Gels ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 26
Author(s):  
Miroslava Špaglová ◽  
Mária Čuchorová ◽  
Martina Čierna ◽  
Silvester Poništ ◽  
Katarína Bauerová

Micro- and nanoemulsions are potential drug solubilizers and penetration enhancers through the high surfactant/co-surfactant content. This study aimed to evaluate the influence of minoxidil (MXD) solubilized in the microemulsions (MEs) on drug release by in vitro/ex vivo diffusion through the semi-permeable membrane Spectra/Por® (Spectrum Laboratory, Gardena, CA, USA) and porcine ear skin. Moreover, a residual amount of drug in the skin after ex vivo diffusion was evaluated. The reference MER, lecithin-containing MEL, and gelatin-containing MEG were characterized in terms of their size, polydispersity index, density, viscosity, electrical conductivity and surface tension. Based on the in vitro diffusion, it can be argued that MEL slowed down the drug release, while MER and MEG have no significant effect compared to the sample, in which propylene glycol (PG) was used as a solubilizer. Determination of the residual drug amount in the skin after 6 h of the ex vivo permeation was demonstrated as the most valuable method to evaluate the effectiveness of the ME’s application. The results indicate that the most optimal MXD permeation enhancers in alginate gel were the natural surfactants containing MEs. MXD solubilization in MEG and MEL had caused more than 5% of the drug remaining in the skin, which is almost a 1.5-fold higher amount compared to the reference gel.


2014 ◽  
Vol 2 (02) ◽  
pp. 07-13 ◽  
Author(s):  
Preeti . ◽  
Murugesan Senthil Kumar

The aim of the present study was to investigate the potential of Transfersomal gel formulations for transdermal delivery of Celecoxib and to evaluate the effect of concentration of Soya PC and Sodium deoxycholate. Transfersomal vesicles containing Soya PC mixed with Sodium deoxycholate and Celecoxib were prepared by conventional rotatory evaporation (Film hydration method) and characterized for various parameters including vesicle shape, size and size distribution, surface morphology, entrapment efficiency, in-vitro and ex-vivo drug release and in-vivo anti-inflammatory activity. Vesicles were also evaluated for skin irritation study and permeation studies.Results of all the studies suggested that CelecoxibTransfersomal gel formulation was therapeutically effective drug delivery system for treatment of Rheumatoid Arthritis.


Author(s):  
Himabindu Peddapalli ◽  
Anjaneyulu Rajagoni ◽  
Preethi Pagilla ◽  
Jerusha Perumala ◽  
Shilpa Puppala ◽  
...  

The purpose of the present research work was to design, assess, and estimate the developed transdermal matrix-type formulation comprising levosulpiride hydrochloride with the objective of enhancing the bioavailability and compliance of the patient. Transdermal films of levosulpiride were developed using a solvent casting method by hydroxypropyl methylcellulose (HPMC) E 15, Eudragit RL 100, and Eudragit RS100. In current research work, propylene glycol and oleic acid was used as plasticizer and permeation enhancers in different fractions. Among the batches, drug content uniformity with all formulations was perceived between 91.6 to 98%. Folding endurance of patches was good and indicates satisfactory flexibility. Developed transdermal films had the necessary physicochemical properties, for example, uniformity of drug content, weight, thickness, folding endurance, and dampness content. Franz diffusion cell was used for in vitro diffusion studies utilizing dialysis membrane as a pervasion boundary. Formulation F5 (Eudragit RL 100-1%, HPMC E15-9%) was found to be best among all batches of its consistent release rate for 12 hours and the extent of drug release 97.76%. F5 was the most palatable formulation as it firmly meets the standards and continuously permeated drugs for 12 hours that can keep up desired therapeutic concentration in plasma. The patches were exposed to transient stability studies and were observed to be constant and stable.


VASA ◽  
2005 ◽  
Vol 34 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Brunner-La Rocca ◽  
Schindler ◽  
Schlumpf ◽  
Saller ◽  
Suter

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.


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