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Article ; Online: Novel Microemulsion Containing Benzocaine and Fusidic Acid Simultaneously: Formulation, Characterization, and In Vitro Evaluation for Wound Healing.

Arpa, Muhammet Davut / Çağlar, Emre Şefik / Güreşçi, Dilara / Sipahi, Hande / Üstündağ Okur, Neslihan

2024 Volume 25, Issue 3, Page(s) 53

Abstract: Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion ... ...

Abstract	Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with -3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile (p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream (p < 0.001). The microemulsion presented lower drug permeation (p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations.
MeSH term(s)	Benzocaine ; Fusidic Acid/pharmacology ; Anesthetics, Local ; Wound Healing ; Water
Chemical Substances	Benzocaine (U3RSY48JW5) ; Fusidic Acid (59XE10C19C) ; Anesthetics, Local ; Water (059QF0KO0R)
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2052070-0
ISSN	1530-9932 ; 1530-9932
ISSN (online)	1530-9932
ISSN	1530-9932
DOI	10.1208/s12249-024-02762-5
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Article ; Online: Improvement of dissolution profile of eplerenone with solidified self-emulsifying drug delivery systems (S-SEDDS).

Ranna, Rawan / Uner, Burcu / Ustundag Okur, Neslihan / Tas, Cetin

Drug development and industrial pharmacy

2023 Volume 49, Issue 4, Page(s) 305–315

Abstract: Context: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug.: Objective: Increasing the solubility of eplerenone by using both ... ...

Abstract	Context: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug. Objective: Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product. Methods: Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. Results: The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow. Conclusion: Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (
MeSH term(s)	Solubility ; Eplerenone ; Emulsions/chemistry ; Drug Delivery Systems/methods ; Drug Liberation ; Surface-Active Agents/chemistry ; Biological Availability
Chemical Substances	Eplerenone (6995V82D0B) ; Emulsions ; Surface-Active Agents
Language	English
Publishing date	2023-05-10
Publishing country	England
Document type	Journal Article
ZDB-ID	751874-2
ISSN	1520-5762 ; 0363-9045
ISSN (online)	1520-5762
ISSN	0363-9045
DOI	10.1080/03639045.2023.2209636
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Zs.A 1335: Show issues

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Article ; Online: The Application of Nanogels as Efficient Drug Delivery Platforms for Dermal/Transdermal Delivery.

Siafaka, Panoraia I / Özcan Bülbül, Ece / Okur, Mehmet Evren / Karantas, Ioannis D / Üstündağ Okur, Neslihan

Gels (Basel, Switzerland)

2023 Volume 9, Issue 9

Abstract: The delivery of active molecules via the skin seems to be an efficient technology, given the various disadvantages of oral drug administration. Skin, which is the largest human organ of the body, has the important role of acting as a barrier for ... ...

Abstract	The delivery of active molecules via the skin seems to be an efficient technology, given the various disadvantages of oral drug administration. Skin, which is the largest human organ of the body, has the important role of acting as a barrier for pathogens and other molecules including drugs; in fact, it serves as a primary defense system blocking any particle from entering the body. Therefore, to overcome the skin barriers and poor skin permeability, researchers implement novel carriers which can effectively carry out transdermal delivery of the molecules. Another significant issue which medical society tries to solve is the effective dermal delivery of molecules especially for topical wound delivery. The application of nanogels is only one of the available approaches offering promising results for both dermal and transdermal administration routes. Nanogels are polymer-based networks in nanoscale dimensions which have been explored as potent carriers of poorly soluble drugs, genes and vaccines. The nanogels present unique physicochemical properties, i.e., high surface area, biocompatibility, etc., and, importantly, can improve solubility. In this review, authors aimed to summarize the available applications of nanogels as possible vehicles for dermal and transdermal delivery of active pharmaceutical ingredients and discuss their future in the pharmaceutical manufacturing field.
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2813982-3
ISSN	2310-2861 ; 2310-2861
ISSN (online)	2310-2861
ISSN	2310-2861
DOI	10.3390/gels9090753
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Article ; Online: Preparation, characterization, and toxicity evaluation of microemulsion formulation containing prunetin for potential oral applications.

Köksal Karayıldırım, Çinel / Üstündağ Okur, Neslihan / Okur, Mehmet Evren / Caglar, Emre Şefik / Nalbantsoy, Ayşe / Alsakını, Karar Ali Mohammed Hasan / Karabay Yavasoglu, Nefise Ülkü

Drug and chemical toxicology

2024 Volume 47, Issue 2, Page(s) 235–242

Abstract: Phytochemicals as therapeutic alternatives can have a fundamental impact on the various stages of inflammation and its resolution. Prunetin is a naturally occurring isoflavone and has been claimed to have numerous therapeutic potentials. The objective of ...

Abstract	Phytochemicals as therapeutic alternatives can have a fundamental impact on the various stages of inflammation and its resolution. Prunetin is a naturally occurring isoflavone and has been claimed to have numerous therapeutic potentials. The objective of this study is preparation, characterization, and toxicity evaluation of microemulsion formulation containing prunetin (PMF) for potential oral applications. With this research, it was targeted to emphasize the way of improving the therapeutic efficacy of natural biomolecules with a nontoxic and effective formulation. In the study, the pseudo-ternary phase diagram was developed and PMF was characterized by conductivity, droplet size, viscosity and pH. Effects against to cytokines (IL-1β and IL-6) and TNF-α levels of the PMF were determined by ELISA technique. Genotoxicity and acute oral toxicity tests were carried out according to OECD guidelines. The results showed that PMF is a colloid system that reduced proinflammatory cytokine levels in LPS-induced macrophage cells compared to the control group. PMF demonstrated no mutagenic activity against TA98, TA100, TA1535, and TA1537
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Isoflavones/pharmacology ; Cytokines ; Mutagens
Chemical Substances	prunetin (1TG4H5H11J) ; Anti-Inflammatory Agents ; Isoflavones ; Cytokines ; Mutagens
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	548368-2
ISSN	1525-6014 ; 0148-0545
ISSN (online)	1525-6014
ISSN	0148-0545
DOI	10.1080/01480545.2023.2282373
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Article ; Online: Novel Ocular Drug Delivery Systems: An Update on Microemulsions.

Üstündağ Okur, Neslihan / Çağlar, Emre Şefik / Siafaka, Panoraia I

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics

2020 Volume 36, Issue 6, Page(s) 342–354

Abstract: Sufficient ophthalmic drug delivery is still challenging for pharmaceutical technologists, despite various scientific efforts. Several ocular drug carriers have been designed to enhance bioavailability by prolonging the drug retention time. One of the ... ...

Abstract	Sufficient ophthalmic drug delivery is still challenging for pharmaceutical technologists, despite various scientific efforts. Several ocular drug carriers have been designed to enhance bioavailability by prolonging the drug retention time. One of the current encouraging approaches is the utilization of colloidal carriers with the characteristic submicron-nanometer size. Microemulsions (MEs) are such colloid systems that present sizes between 5 and 200 nm with significant thermodynamic stability and low surface tension. In addition, MEs as topical ocular carriers can lead to great ocular drug adsorption due to their enhanced retention time. Furthermore, considering that MEs are stable for long time and various temperatures, their ocular application is of great interest. The aim of this study is to cover basic physicochemical principals of ocular MEs such as their possible size, stability, and therapeutic efficacy against various eye disorders. Thus, a comprehensive review for ocular drug delivery systems in the form of MEs that show promising characteristics as their stability and therapeutic efficiency is performed.
MeSH term(s)	Administration, Ophthalmic ; Biological Availability ; Delayed-Action Preparations/administration & dosage ; Delayed-Action Preparations/pharmacokinetics ; Drug Carriers/chemistry ; Drug Compounding/methods ; Drug Compounding/statistics & numerical data ; Drug Delivery Systems/methods ; Drug Design ; Emulsions/administration & dosage ; Emulsions/chemistry ; Emulsions/therapeutic use ; Eye Diseases/drug therapy ; Humans ; Ophthalmic Solutions/administration & dosage ; Ophthalmic Solutions/pharmacokinetics ; Ophthalmic Solutions/therapeutic use ; Particle Size
Chemical Substances	Delayed-Action Preparations ; Drug Carriers ; Emulsions ; Ophthalmic Solutions
Language	English
Publishing date	2020-04-07
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	1237021-6
ISSN	1557-7732 ; 1080-7683
ISSN (online)	1557-7732
ISSN	1080-7683
DOI	10.1089/jop.2019.0135
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Zs.A 2099: Show issues

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Article ; Online: Azelaic acid loaded chitosan and HPMC based hydrogels for treatment of acne: formulation, characterization,

Arpa, Muhammet Davut / Seçen, İkbal Merve / Erim, Ümit Can / Hoş, Ayşegül / Üstündağ Okur, Neslihan

Pharmaceutical development and technology

2022 Volume 27, Issue 3, Page(s) 268–281

Abstract: In this study, hydrogels containing azelaic acid were developed using chitosan or HPMC (1-7%) for local treatment of acne vulgaris. Physicochemical properties such as viscosity, pH and mechanical properties were evaluated. ...

Abstract	In this study, hydrogels containing azelaic acid were developed using chitosan or HPMC (1-7%) for local treatment of acne vulgaris. Physicochemical properties such as viscosity, pH and mechanical properties were evaluated.
MeSH term(s)	Acne Vulgaris/drug therapy ; Chitosan ; Dicarboxylic Acids/chemistry ; Humans ; Hydrogels
Chemical Substances	Dicarboxylic Acids ; Hydrogels ; Chitosan (9012-76-4) ; azelaic acid (F2VW3D43YT)
Language	English
Publishing date	2022-02-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1331774-x
ISSN	1097-9867 ; 1083-7450
ISSN (online)	1097-9867
ISSN	1083-7450
DOI	10.1080/10837450.2022.2038620
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Article ; Online: Enhancing Oral Bioavailability of Domperidone Maleate: Formulation, In-Vitro Permeability Evaluation, In-Caco-2 cell Monolayers and In-Situ Rat Intestinal Permeability Studies.

Üstündağ Okur, Neslihan / Çağlar, Emre Şefik / Kaynak, Mustafa Sinan / Diril, Mine / Özcan, Saniye / Karasulu, Hatice Yeşim

Current drug delivery

2023

Abstract: Background: The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ... ...

Abstract	Background: The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs. Objective: This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and via single-pass intestinal perfusion method. Method: Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, etc. Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for in situ single-pass intestinal perfusion investigations. Results: Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from in situ intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802±0.418×10-4 cm/s). Conclusion: To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.
Language	English
Publishing date	2023-02-14
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2185284-4
ISSN	1875-5704 ; 1567-2018
ISSN (online)	1875-5704
ISSN	1567-2018
DOI	10.2174/1567201820666230214091509
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Article: Current Status of Pediatric Formulations for Chronic and Acute Children' Diseases: Applications and Future Perspectives.

Siafaka, Panoraia / Ipekci, Esra / Caglar, Emre Şefik / Ustundag Okur, Neslihan / Buyukkayhan, Derya

Medeniyet medical journal

2021 Volume 36, Issue 2, Page(s) 152–162

Abstract: Infants and other children can be affected by various acute, chronic and many of them rare illnesses. Developing drugs for children is very challenging since they cannot intake tablets or hard oral solid dosage forms. Besides, most of the prescribed ... ...

Abstract	Infants and other children can be affected by various acute, chronic and many of them rare illnesses. Developing drugs for children is very challenging since they cannot intake tablets or hard oral solid dosage forms. Besides, most of the prescribed pediatric medications are unlicensed. The biggest issue that clinicians have to solve is that dosing in children is not based on weight or surface area of the body, as it happened in adults but is related to age variations in drug absorption, distribution, metabolism, and elimination. Thus, for pediatric patients, various therapeutic approaches have been proposed so as to develop suitable formulations such as liquid dosage forms, flexible capsules, milk-based products, etc. In addition, the administration of current pharmaceutical products to children might lead to some serious side effects which can also happen in adults but with a lower risk. Especially, infants are at high risk of getting poisoned by taking drugs used for adults. Moreover, children are very sensitive to the taste and smell of some pharmaceutical vehicles and can resist to intake them and this situation leads parents to search for tasteless and odorless medications. In this study, the current formulations for various diseases intended to be used in pediatric patients as well as various chronic and acute diseases of childhood are summarized. Authors believe that this review can help professionals who want to work with pediatric formulations to design more efficient and child-friendly drug delivery systems.
Language	English
Publishing date	2021-06-18
Publishing country	Turkey
Document type	Journal Article ; Review
ZDB-ID	3035195-9
ISSN	2149-4606 ; 2149-2042
ISSN (online)	2149-4606
ISSN	2149-2042
DOI	10.5222/MMJ.2021.78476
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Article ; Online: Ocular microemulsion of brinzolamide: Formulation, physicochemical characterization, and in vitro irritation studies based on EpiOcular™ eye irritation assay.

Siafaka, Panoraia I / Çağlar, Emre Şefik / Sipahi, Hande / Charehsaz, Mohammad / Aydın, Ahmet / Üstündağ Okur, Neslihan

Pharmaceutical development and technology

2021 Volume 26, Issue 7, Page(s) 765–778

Abstract: In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of ... ...

Abstract	In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components.
MeSH term(s)	Animals ; Chromatography, High Pressure Liquid ; Emulsions/administration & dosage ; Emulsions/adverse effects ; Emulsions/chemistry ; Eye/drug effects ; Fibroblasts/drug effects ; Mice ; Myristates ; Ophthalmic Solutions/administration & dosage ; Ophthalmic Solutions/adverse effects ; Ophthalmic Solutions/chemistry ; Spectroscopy, Fourier Transform Infrared ; Sulfonamides/administration & dosage ; Sulfonamides/adverse effects ; Sulfonamides/chemistry ; Thiazines/administration & dosage ; Thiazines/adverse effects ; Thiazines/chemistry
Chemical Substances	Emulsions ; Myristates ; Ophthalmic Solutions ; Sulfonamides ; Thiazines ; isopropyl myristate (0RE8K4LNJS) ; brinzolamide (9451Z89515)
Language	English
Publishing date	2021-06-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1331774-x
ISSN	1097-9867 ; 1083-7450
ISSN (online)	1097-9867
ISSN	1083-7450
DOI	10.1080/10837450.2021.1944206
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Article ; Online: Promising nanogels loaded with usnic acid for oral ulcer treatment: development, characterization, and

Coşkunmeriç, Nesrin / Üstündağ Okur, Neslihan / Okur, Mehmet Evren / Ayla, Şule / Yoltaş, Ayşegül / Karavana, Sinem Yaprak

Pharmaceutical development and technology

2021 Volume 26, Issue 4, Page(s) 431–443

Abstract: This study aimed to present an effective formulation targeting oral ulcers that will remain in the application site for a longer period, reducing the frequency of administration. As a candidate formulation, usnic acid (UA) was loaded into the optimum ... ...

Abstract	This study aimed to present an effective formulation targeting oral ulcers that will remain in the application site for a longer period, reducing the frequency of administration. As a candidate formulation, usnic acid (UA) was loaded into the optimum nanogels. The characterization studies included physical, rheological, and bioadhesive properties as well as
MeSH term(s)	Adhesiveness ; Animals ; Anti-Infective Agents/administration & dosage ; Anti-Infective Agents/pharmacology ; Bacillus cereus/drug effects ; Benzofurans/administration & dosage ; Benzofurans/pharmacology ; Delayed-Action Preparations ; Disease Models, Animal ; Drug Liberation ; Male ; Nanogels ; Oral Ulcer/drug therapy ; Oral Ulcer/pathology ; Particle Size ; Rabbits ; Rheology ; Wound Healing/drug effects
Chemical Substances	Anti-Infective Agents ; Benzofurans ; Delayed-Action Preparations ; Nanogels ; usnic acid (0W584PFJ77)
Language	English
Publishing date	2021-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1331774-x
ISSN	1097-9867 ; 1083-7450
ISSN (online)	1097-9867
ISSN	1083-7450
DOI	10.1080/10837450.2021.1885441
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