scholarly journals Biological Evaluation of Oil-in-Water Microemulsions as Carriers of Benzothiophene Analogues for Dermal Applications

Biomimetics ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 10
Author(s):  
Ioanna Theochari ◽  
Tanja Ilic ◽  
Ines Nicolic ◽  
Vladimir Dobricic ◽  
Alia Tenchiou ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Drug Carrier ◽  
Tween 80 ◽  
Biological Evaluation ◽  
Hair Follicles ◽  
Bioactive Molecules ◽  
Transdermal Administration ◽  
Thiazolyl Blue Tetrazolium Bromide ◽  
Oil In Water

During the last decade, many studies have been reported on the design and formulation of novel drug delivery systems proposed for dermal or transdermal administration. The efforts focus on the development of biocompatible nanodispersions that can be delivered to the skin and treat severe skin disorders, including cancer. In this context, oil-in-water (O/W) microemulsions have been developed to encapsulate and deliver lipophilic bioactive molecules for dermal application. An O/W biocompatible microemulsion composed of PBS buffer, Tween 80, and triacetin was assessed for its efficacy as a drug carrier of DPS-2, a lead compound, initially designed in-house to inhibit BRAFV600E oncogenic kinase. The system was evaluated through both in vitro and ex vivo approaches. The cytotoxic effect, in the presence and absence of DPS-2, was examined through the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay using various cell lines. Further investigation through Western blotting revealed that cells died of necrosis. Porcine ear skin was used as a skin model to evaluate the degree of permeation of DPS-2 through skin and assess its retention. Through the ex vivo experiments, it was clarified that encapsulated DPS-2 was distributed within the full thickness of the stratum corneum (SC) and had a high affinity to hair follicles.

scholarly journals PSMA-D4 Radioligand for Targeted Therapy of Prostate Cancer: Synthesis, Characteristics and Preliminary Assessment of Biological Properties

2021 ◽  
Vol 22 (5) ◽  
pp. 2731
Author(s):  
Piotr Garnuszek ◽  
Urszula Karczmarczyk ◽  
Michał Maurin ◽  
Arkadiusz Sikora ◽  
Jolanta Zaborniak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapy ◽  
Ex Vivo ◽  
Specific Binding ◽  
Biological Evaluation ◽  
In Vitro Assays ◽  
The Novel ◽  
Distribution Profile ◽  
System L

A new PSMA ligand (PSMA-D4) containing the Glu-CO-Lys pharmacophore connected with a new linker system (L-Trp-4-Amc) and chelator DOTA was developed for radiolabeling with therapeutic radionuclides. Herein we describe the synthesis, radiolabeling, and preliminary biological evaluation of the novel PSMA-D4 ligand. Synthesized PSMA-D4 was characterized using TOF-ESI-MS, NMR, and HPLC methods. The novel compound was subject to molecular modeling with GCP-II to compare its binding mode to analogous reference compounds. The radiolabeling efficiency of PSMA-D4 with 177Lu, 90Y, 47Sc, and 225Ac was chromatographically tested. In vitro studies were carried out in PSMA-positive LNCaP tumor cells membranes. The ex vivo tissue distribution profile of the radioligands and Cerenkov luminescence imaging (CLI) was studied in LNCaP tumor-bearing mice. PSMA-D4 was synthesized in 24% yield and purity >97%. The radio complexes were obtained with high yields (>97%) and molar activity ranging from 0.11 to 17.2 GBq mcmol−1, depending on the radionuclide. In vitro assays confirmed high specific binding and affinity for all radiocomplexes. Biodistribution and imaging studies revealed high accumulation in LNCaP tumor xenografts and rapid clearance of radiocomplexes from blood and non-target tissues. These render PSMA-D4 a promising ligand for targeted therapy of prostate cancer (PCa) metastases.

scholarly journals Synthesis, gallium-68 radiolabelling and biological evaluation of a series of triarylphosphonium-functionalized DO3A chelators

2018 ◽  
Vol 47 (43) ◽  
pp. 15448-15457 ◽  
Author(s):  
Adam J. Smith ◽  
Peter J. Gawne ◽  
Michelle T. Ma ◽  
Philip J. Blower ◽  
Richard Southworth ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Biological Evaluation ◽  
Tumour Cells ◽  
Isolated Hearts ◽  
Gallium 68

Gallium-68 chelators with tunable lipophilicities were synthesised, and assessed in both in vitro tumour cells and ex vivo isolated hearts.

scholarly journals Fabrication of Transgelosomes for Enhancing the Ocular Delivery of Acetazolamide: Statistical Optimization, In Vitro Characterization, and In Vivo Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 465 ◽  
Author(s):  
Eman A. Mazyed ◽  
Abdelaziz E. Abdelaziz
Keyword(s):  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Tween 80 ◽  
Ocular Delivery ◽  
Ethanol Injection ◽  
In Vitro Characterization ◽  
Span 60 ◽  
In Vivo Characterization

Acetazolamide (ACZ) is a potent carbonic anhydrase inhibitor that is used for the treatment of glaucoma. Its oral administration causes various undesirable side effects. This study aimed to formulate transgelosomes (TGS) for enhancing the ocular delivery of ACZ. ACZ-loaded transfersomes were formulated by the ethanol injection method, using phosphatidylcholine (PC) and different edge activators, including Tween 80, Span 60, and Cremophor RH 40. The effects of the ratio of lipid to surfactant and type of surfactant on % drug released after 8 h (Q8h) and entrapment efficiency (EE%) were investigated by using Design-Expert software. The optimized formula was formulated as TGS, using poloxamers as gelling agents. In vitro and in vivo characterization of ACZ-loaded TGS was performed. According to optimization study, F8 had the highest desirability value and was chosen as the optimized formula for preparing TGS. F8 appeared as spherical elastic nanovesicles with Q8h of 93.01 ± 3.76% and EE% of 84.44 ± 2.82. Compared to a free drug, TGS exhibited more prolonged drug release of 71.28 ± 0.46% after 8 h, higher ex vivo permeation of 66.82 ± 1.11% after 8 h and a significant lowering of intraocular pressure (IOP) for 24 h. Therefore, TGS provided a promising technique for improving the corneal delivery of ACZ.

scholarly journals ENHANCING THE SUNSCREEN EFFICACY OF BEMOTRIZINOL MICROPIGMENT BY USING O/W NANOEMULSION TOPICAL PREPARATIONS

2019 ◽  
pp. 47-56
Author(s):  
Dina Medhat Hashim ◽  
Nermin Mohamed Sheta ◽  
Vivian Samir Elwazzan ◽  
Wedad Saed Sakran
Keyword(s):  
Ex Vivo ◽  
In Vitro Release ◽  
Tween 80 ◽  
Size Analysis ◽  
Isopropyl Myristate ◽  
Tape Stripping ◽  
Protection Factor ◽  
Potential Measurement ◽  
Optimum Formula

Objective: Bemotrizinol (BEMT) is the most efficient broad-spectrum UV-absorber having a dual mechanism of action in absorbing and reflecting photons. The main objective of this work was to develop successful oil in water (o/w) nanoemulsion for improving the solubility of BEMT and its protective characteristics. Methods: Pseudo-ternary phase diagrams were constructed using labrafac PG and isopropyl myristate as oil phase, tween 80 as surfactant (S) and cremophor EL as cosurfactant (CoS) the ratio of S/CoS was determined according to highest percent of water incorporation to the system. Full factorial study design (24) using Design-Expert® software was adopted to study the effect of four independent variables namely: oil type, oil concentration, S/CoSmix (3:1) concentrations and BEMT concentration on the particle size and the in vitro release at 2 h (Q2h) of the prepared nanoemulsion formulae. Two systems each of eight formulae were developed and evaluated through droplet size analysis, zeta potential measurement, refractive index, in vitro drug release and according to the desirability value two formulae (F6 and F14) were used for further evaluations including in vitro sun protection factor (SPF), ex-vivo deposition by tape stripping technique, permeation test and photostability study. Results: Formula (F14) was chosen as the optimum formula having an in vitro SPF of 16.08±0.39, lowest permeation of 140±0.06 μg/cm2after six h and highest photostability (t90% = 168.02) after 120 min. Conclusion: Despite the poor solubility of bemotrizinol, it could be enhanced by novel drug delivery systems with good SPF value while maintaining its photostability.

FORMULATION AND OPTIMIZATION OF TOPICAL NANOEMULSION BASED GEL OF MOMETASONE FUROATE USING 32 FULL FACTORIAL DESIGN

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (06) ◽  
pp. 19-29
Author(s):  
Bhupendra G. Prajapati ◽  
◽  
Malay Jivani ◽  
Himanshu Paliwal ◽  
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
In Vitro Release ◽  
Tween 80 ◽  
Stability Study ◽  
Mometasone Furoate ◽  
Gelling Agent ◽  
Topical Formulation ◽  
Topical Gel

Mometasone furoate (MF) is a glucocorticoid prodrug that faces the problem of poor aqueous solubility. Nanoemulsion-based topical gel of MF was formulated to enhance its solubility and potential of treating skin conditions. The selection of oil, surfactant and co-surfactant was done based on their solubility with the drug. The nanoemulsion was prepared using rose oil as the oil phase. Tween 80 and Transcutol P were used as surfactant and co-surfactant and they were blended in different ratios (1:0, 1:1, 2:1 and 3:1 w/w). The pseudo ternary diagrams were developed using these excipients and formulations exhibiting considerable nanoemulsion region were selected. The formulations were optimized by using Design Expert software for the globule size and cumulative percent release. The nanoemulsion formulations were characterized for in vitro release and stability study. The optimized nanoemulsions consisting of 2 % w/w oil, 30 % w/w Smix (Surfactant: Co-surfactant) and 67.9 % w/w water were consolidated into Carbopol 940 gelling agent to prepare three nanoemulsion-based gel formulations or nanoemulgels (NEG1-NEG3). Nanoemulgels were evaluated for their stability and ex vivo permeation of MF. The outcomes suggested that skin permeation of MF from all the nanoemulgel formulations was significantly enhanced as compared to the marketed mometasone furoate topical formulation.

Synthesis and biological evaluation of α-sulfonamido-N-adamantanecarboxamide derivatives as 11β-HSD1 inhibitors

MedChemComm ◽  
2015 ◽  
Vol 6 (7) ◽  
pp. 1360-1369
Author(s):  
Young Hoon Kim ◽  
Seung Kyu Kang ◽  
Gwi Bin Lee ◽  
Kyu Myung Lee ◽  
Jaladi Ashok Kumar ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Biological Evaluation ◽  
Synthesis And Biological Evaluation

A series of α-sulfonamido-N-adamantanecarboxamide derivatives was synthesized and shown to have good in vitro and ex vivo efficacy.

scholarly journals 5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3747
Author(s):  
Oumaima Jaouadi ◽  
Inès Limam ◽  
Mohamed Abdelkarim ◽  
Emna Berred ◽  
Ahlem Chahbi ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Potential Role ◽  
Cholesterol Metabolism ◽  
Ex Vivo ◽  
Myeloma Cell ◽  
Bioactive Molecules ◽  
Myeloma Cells ◽  
Acquired Drug Resistance ◽  
Anti Tumor Activity

Multiple myeloma (MM) is an incurable plasma cell malignancy with frequent patient relapse due to innate or acquired drug resistance. Cholesterol metabolism is reported to be altered in MM; therefore, we investigated the potential anti-myeloma activity of two cholesterol derivatives: the 5,6 α- and 5,6 β-epoxycholesterol (EC) isomers. To this end, viability assays were used, and isomers were shown to exhibit important anti-tumor activity in vitro in JJN3 and U266 human myeloma cell lines (HMCLs) and ex vivo in myeloma patients’ sorted CD138+ malignant cells. Moreover, we confirmed that 5,6 α-EC and 5,6 β-EC induced oxiapoptophagy through concomitant oxidative stress and caspase-3-mediated apoptosis and autophagy. Interestingly, in combination treatment a synergistic interaction was observed between 5,6 α-EC and 5,6 β-EC on myeloma cells. These data highlight a striking anti-tumor activity of 5,6 α-EC and 5,6 β-EC bioactive molecules against human myeloma cells, paving the way for their potential role in future therapeutic strategies in MM.

scholarly journals Vegetable Oil-Based Self-Microemulsifying Drug Delivery System of Eprosartan Mesylate: in vitro and ex vivo Evaluation

2021 ◽  
Vol 33 (9) ◽  
pp. 2182-2190
Author(s):  
Sabitri Bindhani ◽  
Snehamayee Mohapatra ◽  
Rajat Kumar Kar
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Delivery System ◽  
Intestinal Permeability ◽  
Delivery System ◽  
Ex Vivo ◽  
Tween 80 ◽  
Stability Study ◽  
Potent Drug

This study was planned to increase the intestinal permeability and thereby bioavailability of eprosartan mesylate (EPM) by designing a self-microemulsifying drug delivery system (SMEDDS) by the use of vegetable oils. Various SMEDDS-based formulations were prepared with oleic acid and peppermint oil. Tween 80 was used as surfactant and PEG 400 as co-surfactant. Pseudo ternary phase diagrams were constructed for identifying emulsification region between 1:1, 1:2, 2:1, 3:1 ratio of SCOS mix. Eight batches of SMEDDS were found to be thermodynamically stable and from which SMEDDSOF9 and PF5 were best formulations due to their highest drug content, minimum particle size. They have shown highest release of drug in vitro and higher in vitro drug diffusion and ex vivo permeation analysis than pure drug. FTIR study ascertained no incompatibility between drug and excipients present in formulation. From the accelerated stability study, slight effect on particle size and zeta potential, assay content along with cumulative % of drug release was found. The results demonstrated the SMEDDS of EPM are potent drug delivery system to increase dissolution rate and bioavailability of drug via increased intestinal permeability and consequently improving the therapeutic efficacy of eprosartan mesylate.

scholarly journals Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lupeng Zeng ◽  
Huaying Wang ◽  
Wanhua Shi ◽  
Lingfan Chen ◽  
Tingting Chen ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Retention Rate ◽  
Drug Carrier ◽  
Heating System ◽  
Melanoma Cells ◽  
Transdermal Administration ◽  
Promising Perspective ◽  
And Storage

Abstract Background Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. Results Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. Conclusions Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system. Graphical Abstract

scholarly journals DEVELOPMENT AND CHARACTERIZATION OF INDOMETHACIN-LOADED MUCOADHESIVE NANOSTRUCTURED LIPID CARRIERS FOR TOPICAL OCULAR DELIVERY

2018 ◽  
Vol 10 (2) ◽  
pp. 91 ◽  
Author(s):  
Pattravee Niamprem ◽  
S. P. Srinivas ◽  
Waree Tiyaboonchai
Keyword(s):  
Ex Vivo ◽  
In Vitro Release ◽  
Tween 80 ◽  
Nanostructured Lipid Carriers ◽  
Burst Release ◽  
Prolonged Release ◽  
Polyethylene Glycol 400 ◽  
Safe Delivery ◽  
Vitro Release

Objective: To develop and characterize indomethacin loaded-nanostructured lipid carriers (IND-NLCs) for topical ophthalmic delivery with different particle sizes and polymer coating to improve the mucoadhesive property on the ocular surface.Methods: Nanostructured lipid carriers (NLCs) with different solid lipids and surfactants were prepared by the high-pressure homogenization technique. The optimized IND-NLCs was coated with polyethylene glycol 400 (PEG). The physicochemical properties and entrapment efficacy (EE) were examined. In vitro release studies were investigated using the shake-flask method. Ex vivo mucoadhesive studies were assessed by the wash-off test. In addition, the cytotoxicity was assessed by the short time exposure test.Results: IND-NLCs of ~300 and ~40 nm in diameter were successfully produced with a zeta potential of -30 mV and EE of 60–70 %. IND-NLCs prepared with Tween 80 as surfactant could be sterilized by autoclaving. The PEG coating of IND-NLCs did not affect either the particle size or EE. In vitro release showed a prolonged release for 360 min with a burst release of 50-60% occurring within 5 min. The smaller-sized IND-NLCs showed slightly faster release rates and better mucoadhesion to cornea compared to the larger IND-NLCs. PEG-coated IND-NLCs showed the highest mucoadhesion. In addition, IND-NLCs showed less cytotoxicity compared to IND alone. Conclusion: The small and PEG-coated NLCs represents a potentially useful carrier for safe delivery of indomethacin to the ocular surface with increased residence time.

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