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Article ; Online: Enhanced delivery of naproxen to the viable epidermis from an activated poly N-isopropylacrylamide (PNIPAM) Nanogel: Skin penetration, modulation of COX-2 expression and rat paw oedema.

Yurdasiper, Aysu / Ertan, Gokhan / Heard, Charles M

Nanomedicine : nanotechnology, biology, and medicine

2018 Volume 14, Issue 7, Page(s) 2051–2059

Abstract: Stimulus-responsive drug-loaded poly (N-isopropylacrylamide) nanogels were examined as a means of enhancing the delivery of naproxen into skin ex vivo. Following massaging into skin, the epidermis was probed (with and without base activation) for depth ... ...

Abstract	Stimulus-responsive drug-loaded poly (N-isopropylacrylamide) nanogels were examined as a means of enhancing the delivery of naproxen into skin ex vivo. Following massaging into skin, the epidermis was probed (with and without base activation) for depth penetration and transdermal delivery of drug, and anti-inflammatory activity in the relative levels of COX-2 expression. Rat paw oedema testing was used to determine anti-inflammatory effects in vivo. When activated by sodium carbonate, particle size reduced by 19%. Tape stripping revealed significantly greater delivery of naproxen into the epidermis for the activated nanogel and the steady state flux was enhanced 2.8-fold. With base-activation COX-2 was 50% lower than non-activated, and this trend was confirmed by immunostaining, and by the reduction of rat paw swelling which provided ex vivo - in vivo corroboration. A mechanism of action is proposed. In conclusion, stimulus-responsive nanogels have potential for enhancing dermal drug delivery and therapeutic outcomes in inflammatory skin diseases.
MeSH term(s)	Acrylamides/chemistry ; Administration, Cutaneous ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Carrageenan/toxicity ; Cyclooxygenase 2/genetics ; Cyclooxygenase 2/metabolism ; Drug Delivery Systems ; Edema/chemically induced ; Edema/drug therapy ; Epidermal Cells ; Epidermis/drug effects ; Epidermis/metabolism ; Gene Expression Regulation/drug effects ; Male ; Naproxen/administration & dosage ; Naproxen/chemistry ; Naproxen/pharmacology ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/chemistry ; Polyethyleneimine/administration & dosage ; Polyethyleneimine/chemistry ; Polymers/chemistry ; Rats ; Rats, Wistar ; Skin/cytology ; Skin/drug effects ; Skin/metabolism
Chemical Substances	Acrylamides ; Anti-Inflammatory Agents, Non-Steroidal ; NanoGel ; Polymers ; Polyethylene Glycols (3WJQ0SDW1A) ; Naproxen (57Y76R9ATQ) ; Carrageenan (9000-07-1) ; Polyethyleneimine (9002-98-6) ; N-isopropylacrylamide (B7GFF17L9U) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Ptgs2 protein, rat (EC 1.14.99.1)
Language	English
Publishing date	2018-06-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2018.05.017
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Article: Drug transport mechanism of oral antidiabetic nanomedicines.

Gundogdu, Evren / Yurdasiper, Aysu

International journal of endocrinology and metabolism

2014 Volume 12, Issue 1, Page(s) e8984

Abstract: Context: Over the last few decades, extensive efforts have been made worldwide to develop nanomedicine delivery systems, especially via oral route for antidiabetic drugs. Absorption of insulin is hindered by epithelial cells of gastrointestinal tract, ... ...

Abstract	Context: Over the last few decades, extensive efforts have been made worldwide to develop nanomedicine delivery systems, especially via oral route for antidiabetic drugs. Absorption of insulin is hindered by epithelial cells of gastrointestinal tract, acidic gastric pH and digestive enzymes. Evidence acquisition: Recent reports have identified and explained the beneficial role of several structural molecules like mucoadhesive polymers (polyacrylic acid, sodium alginate, chitosan) and other copolymers for the efficient transport and release of insulin to its receptors. Results: Insulin nanomedicines based on alginate-dextran sulfate core with a chitosan-polyethylene glycol-albumin shell reduced glycaemia in a dose dependent manner. Orally available exendin-4 formulations exerted their effects in a time dependent manner. Insulin nanoparticles formed by using alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin showed a threefold increase of the hypoglycemic effect in comparison to free insulin in animal models. Solid lipid nanoparticles showed an enhancement of the bioavailability of repaglinide (RG) within optimized solid lipid nanoparticle formulations when compared with RG alone. Conclusions: Nanoparticles represent multiparticulate delivery systems designed to obtain prolonged or controlled drug delivery and to improve bioavailability as well as stability. Nanoparticles can also offer advantages like limiting fluctuations within therapeutic range, reducing side effects, protecting drugs from degradation, decreasing dosing frequency, and improving patient compliance and convenience.
Language	English
Publishing date	2014-01-01
Publishing country	Iran
Document type	Journal Article ; Review
ZDB-ID	2744447-8
ISSN	1726-9148 ; 1726-913X
ISSN (online)	1726-9148
ISSN	1726-913X
DOI	10.5812/ijem.8984
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Article ; Online: Modification of solid lipid nanoparticles loaded with nebivolol hydrochloride for improvement of oral bioavailability in treatment of hypertension: polyethylene glycol versus chitosan oligosaccharide lactate.

Üstündağ-Okur, Neslihan / Yurdasiper, Aysu / Gündoğdu, Evren / Gökçe, Evren Homan

Journal of microencapsulation

2016 Volume 33, Issue 1, Page(s) 30–42

Abstract: Nebivolol (NB)-loaded solid lipid nanoparticles (SLNs) were prepared and modified with chitosan oligosaccharide lactate (COL) and polyethylene glycol (PEG) stearate for improvement of its oral bioavailability. Compritol, poloxamer and lecithin were used ... ...

Abstract	Nebivolol (NB)-loaded solid lipid nanoparticles (SLNs) were prepared and modified with chitosan oligosaccharide lactate (COL) and polyethylene glycol (PEG) stearate for improvement of its oral bioavailability. Compritol, poloxamer and lecithin were used for the preparation of SLNs by homogenisation method. After in vitro characterisation effect of lipase, pepsin, or pancreatin on degradation and release rate were investigated. Cytotoxicity and permeation were studied on Caco-2 cells. As COL concentration increased in SLNs, size and zeta potential increased. PEG concentration was reversely proportional to particle size with no change in zeta potential. Encapsulation efficiencies (EEs) were determined as 84-98%. DSC confirmed solubilisation of NB in lipid matrix. A sustained release with no burst effect was determined. The presence of enzymes affected the release. SLNs did not reveal cytotoxicity and highest permeability was obtained with PEG modification. PEG-modified SLNs could be offered as a promising strategy for oral delivery of NB.
MeSH term(s)	Administration, Oral ; Caco-2 Cells ; Chitosan/chemistry ; Chitosan/pharmacokinetics ; Chitosan/pharmacology ; Humans ; Hypertension/drug therapy ; Nanoparticles/chemistry ; Nebivolol/chemistry ; Nebivolol/pharmacokinetics ; Nebivolol/pharmacology ; Oligosaccharides/chemistry ; Oligosaccharides/pharmacokinetics ; Oligosaccharides/pharmacology ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/pharmacokinetics ; Polyethylene Glycols/pharmacology
Chemical Substances	Oligosaccharides ; Nebivolol (030Y90569U) ; Polyethylene Glycols (30IQX730WE) ; Chitosan (9012-76-4) ; polyethylene glycol 1000 (U076Q6Q621)
Language	English
Publishing date	2016-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	843632-0
ISSN	1464-5246 ; 0265-2048
ISSN (online)	1464-5246
ISSN	0265-2048
DOI	10.3109/02652048.2015.1094532
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Article ; Online: A novel preparation method for organogels: high-speed homogenization and micro-irradiation.

Gökçe, Evren Homan / Yurdasiper, Aysu / Korkmaz, Emrah / Özer, Özgen

AAPS PharmSciTech

2013 Volume 14, Issue 1, Page(s) 391–397

Abstract: The aim of this work was to prepare organogels of Carbopol 974P NF (C974) in PEG 400 by using a novel technique, high-speed homogenization followed by microwave heating. Triclosan (TCS) was used as a model drug. C974, at concentrations ranging between 2% ...

Abstract	The aim of this work was to prepare organogels of Carbopol 974P NF (C974) in PEG 400 by using a novel technique, high-speed homogenization followed by microwave heating. Triclosan (TCS) was used as a model drug. C974, at concentrations ranging between 2% and 4%, was dispersed in 25 ml of PEG 400, and the dispersion was homogenised for 5 min at 24,000 rpm. The dispersion was either heated at 80°C in water bath under mechanic stirring at 200 rpm or exposed to micro-irradiation (1,200 W/1 h) for 2 min. The formulations prepared with both methods performed a well-structured gel matrix characteristic at 3% and 4% of C974 concentrations. As the concentrations of the polymer increased, the elastic properties also increased. The viscosity profiles indicated a shear-thinning system. DSC data revealed that TCS was dissolved in gel. Skin accumulation ability of TCS had been improved by these novel organogels regardless of the preparation method. TCS was still microbiologically effective after the microwave process was applied. It was determined that microwave heating is a suitable method to obtain C974 organogels. This novel production technique developed might be promising especially in industrial scale when the dramatic reduction in the preparation time and energy were considered.
MeSH term(s)	Calorimetry, Differential Scanning ; Gels ; Magnetic Resonance Spectroscopy ; Organic Chemicals ; Rheology ; Skin/metabolism
Chemical Substances	Gels ; Organic Chemicals
Language	English
Publishing date	2013-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2052070-0
ISSN	1530-9932 ; 1530-9932
ISSN (online)	1530-9932
ISSN	1530-9932
DOI	10.1208/s12249-013-9922-8
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Article ; Online: Enhanced topical delivery and anti-inflammatory activity of methotrexate from an activated nanogel.

Singka, Gillian S Leslie / Samah, Nor Abu / Zulfakar, Mohd H / Yurdasiper, Aysu / Heard, Charles M

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

2010 Volume 76, Issue 2, Page(s) 275–281

Abstract: This work examined the effect of sodium carbonate (Na(2)CO(3)) on the topical delivery of methotrexate (MTX) from a loaded nanogel in vitro and the modulation of prostaglandin E(2) (PGE(2)) production in skin ex vivo. A nanogel based on co-polymerised N- ... ...

Abstract	This work examined the effect of sodium carbonate (Na(2)CO(3)) on the topical delivery of methotrexate (MTX) from a loaded nanogel in vitro and the modulation of prostaglandin E(2) (PGE(2)) production in skin ex vivo. A nanogel based on co-polymerised N-isopropylacrylamide (NIPAM) and butylacrylate (BA) was synthesized, characterized and loaded with MTX. Finite doses were then applied to excised porcine epidermal membranes mounted in Franz diffusion cells, followed by the addition of saturated aqueous Na(2)CO(3). For comparison, the addition of half-saturated Na(2)CO(3) was examined along with loaded nanogel alone. The same treatments were applied to Silastic membrane and full-thickness porcine ear skin ex vivo, which was then treated with radioimmunoprecipitation buffer and probed for levels of PGE(2) using a commercial enzyme immunoassay kit. The MTX-loaded nanogel, which demonstrated de-swelling by 7% over the range 25-37°C, provided a MTX flux of 1.4±0.3ngcm(-2)h(-1); this increased to 3.1±0.22ngcm(-2)h(-1) upon the addition of saturated aqueous Na(2)CO(3) (p<0.05). Lag times were 6 and ∼0h, respectively. Similar results were obtained using half-saturated aqueous Na(2)CO(3). No permeation was detected across Silastic membrane. PGE(2) levels for water (control) and saturated aqueous Na(2)CO(3) were similar, but reduced by 33% when the MTX-loaded nanogel was applied, and by 57% when this was followed by the application of saturated aqueous Na(2)CO(3) (p<0.01). A novel mechanism is proposed whereby the change in temperature experienced by the nanogel as it penetrated skin induced de-swelling and expulsion of MTX in situ. The added Na(2)CO(3) lead to further solubilisation and MTX release, hence increasing the concentration gradient, flux and reducing PGE(2) production.
MeSH term(s)	Acrylamides/chemistry ; Acrylates/chemistry ; Administration, Cutaneous ; Animals ; Carbonates/chemistry ; Dermatologic Agents/administration & dosage ; Dermatologic Agents/pharmacokinetics ; Dermatologic Agents/pharmacology ; Dinoprostone/biosynthesis ; Excipients/chemistry ; Gels ; Methotrexate/administration & dosage ; Methotrexate/pharmacokinetics ; Methotrexate/pharmacology ; Nanoparticles ; Permeability ; Skin Absorption ; Swine ; Temperature ; Time Factors
Chemical Substances	Acrylamides ; Acrylates ; Carbonates ; Dermatologic Agents ; Excipients ; Gels ; sodium carbonate (45P3261C7T) ; n-butyl acrylate (705NM8U35V) ; N-isopropylacrylamide (B7GFF17L9U) ; Dinoprostone (K7Q1JQR04M) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2010-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1065368-5
ISSN	1873-3441 ; 0939-6411
ISSN (online)	1873-3441
ISSN	0939-6411
DOI	10.1016/j.ejpb.2010.06.014
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Zs.B 1651: Show issues

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Article ; Online: Studies on mefenamic acid microparticles: formulation, in vitro release, and in situ studies in rats.

Sevgi, Ferhan / Yurdasiper, Aysu / Kaynarsoy, Buket / Turunç, Ezgi / Güneri, Tamer / Yalçin, Ayfer

AAPS PharmSciTech

2009 Volume 10, Issue 1, Page(s) 104–112

Abstract: In this study, we investigated the in vitro characteristics of mefenamic acid (MA) microparticles as well as their effects on DNA damage. MA-loaded chitosan and alginate beads were prepared by the ionotropic gelation process. Microsponges containing MA ... ...

Abstract	In this study, we investigated the in vitro characteristics of mefenamic acid (MA) microparticles as well as their effects on DNA damage. MA-loaded chitosan and alginate beads were prepared by the ionotropic gelation process. Microsponges containing MA and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method. The microparticles were characterized in terms of particle size, surface morphology, encapsulation efficiency, and in vitro release profiles. Most of the formulation variables manifested an influence on the physical characteristics of the microparticles at varying degrees. We also studied the effects of MA, MA-loaded microparticles, and three different polymers on rat brain cortex DNA damage. Our results showed that DNA damage was higher in MA-loaded Eudragit microsponges than MA-loaded biodegradable chitosan or alginate microparticles.
MeSH term(s)	Acrylic Resins/chemistry ; Alginates/chemistry ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Cerebral Cortex/drug effects ; Cerebral Cortex/pathology ; Chemistry, Pharmaceutical ; Chitosan/chemistry ; DNA Damage ; Dosage Forms ; Drug Carriers ; Drug Compounding ; Excitatory Amino Acid Agonists/toxicity ; Glucuronic Acid/chemistry ; Hexuronic Acids/chemistry ; Kainic Acid/toxicity ; Kinetics ; Mefenamic Acid/chemistry ; Mefenamic Acid/pharmacology ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Solubility ; Technology, Pharmaceutical/methods
Chemical Substances	Acrylic Resins ; Alginates ; Anti-Inflammatory Agents, Non-Steroidal ; Dosage Forms ; Drug Carriers ; Excitatory Amino Acid Agonists ; Hexuronic Acids ; Neuroprotective Agents ; Eudragit RS (33434-24-1) ; Mefenamic Acid (367589PJ2C) ; Glucuronic Acid (8A5D83Q4RW) ; Chitosan (9012-76-4) ; Kainic Acid (SIV03811UC)
Language	English
Publishing date	2009-01-29
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/s12249-008-9183-0
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Article: Acceleration of in vitro dissolution studies of sustained release dosage form of theophylline and in vitro-in vivo evaluations in terms of correlations.

Ertan, Gökhan / Karasulu, Ercüment / Ozgüney, Işık / Karasulu, Yeşim / Apaydın, Sebnem / Kantarcı, Gülten / Yurdasiper, Aysu / Ege, Mehmet Ali

European journal of drug metabolism and pharmacokinetics

2011 Volume 36, Issue 4, Page(s) 243–248

Abstract: The aim of the study was to accelerate the dissolution of the sustained release dosage forms using both elevated temperature and high rpm rates. Teokap(®) SR 200 mg pellets were tested by in vitro sustained and accelerated dissolution studies using USP ... ...

Abstract	The aim of the study was to accelerate the dissolution of the sustained release dosage forms using both elevated temperature and high rpm rates. Teokap(®) SR 200 mg pellets were tested by in vitro sustained and accelerated dissolution studies using USP XXIII rotating paddle method. Sustained dissolution studies were carried out for 12 h in phosphate buffer at 37 ± 0.5°C and 50 rpm. Accelerated dissolution studies were performed for 48 min in distilled water at 90 ± 1°C and 250 rpm. The results obtained from accelerated and sustained dissolution studies were correlated using both linear and linear kinetic correlation methods by a computer program. While r (2) and maximum error between calculated and observed drug release rates were found to be 0.9129 and 15.9%, respectively, in linear correlation method, these values were observed as 0.9938 and 3.6%, respectively, in linear kinetic correlation method. In vivo plasma concentration data were obtained from six New Zealand rabbits after administration of a single dose of Teokap(®) SR 200 mg pellet. Then, the results of in vivo study were evaluated with in vitro accelerated and sustained dissolution results by applying them to in vitro-in vivo linear correlations. As a result of these correlations, it was shown that the in vitro correlation plots were very similar to the plot which was obtained by the in vivo study (f (2) = 73.81-77.11). This study suggested a way to prevent the loss of time for routine dissolution studies of sustained release preparations for quality control procedures using in vitro accelerated dissolution tests. The storage and quarantine periods of the product in process and process controls in the manufactories could be shortened by this method. Calculation of the in vivo performance of sustained release dosage forms using the results of the accelerated dissolution studies may be counted as another advantage of the method.
MeSH term(s)	Animals ; Delayed-Action Preparations ; Male ; Rabbits ; Solubility ; Theophylline/administration & dosage ; Theophylline/chemistry
Chemical Substances	Delayed-Action Preparations ; Theophylline (C137DTR5RG)
Language	English
Publishing date	2011-07-08
Publishing country	France
Document type	Journal Article
ZDB-ID	196729-0
ISSN	2107-0180 ; 0378-7966 ; 0398-7639
ISSN (online)	2107-0180
ISSN	0378-7966 ; 0398-7639
DOI	10.1007/s13318-011-0049-6
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Article ; Online: Enhanced delivery of naproxen to the viable epidermis from an activated poly N-isopropylacrylamide (PNIPAM) Nanogel: Skin penetration, modulation of COX-2 expression and rat paw oedema.

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Article: Drug transport mechanism of oral antidiabetic nanomedicines.

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Article ; Online: Modification of solid lipid nanoparticles loaded with nebivolol hydrochloride for improvement of oral bioavailability in treatment of hypertension: polyethylene glycol versus chitosan oligosaccharide lactate.

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Article ; Online: A novel preparation method for organogels: high-speed homogenization and micro-irradiation.

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Article ; Online: Enhanced topical delivery and anti-inflammatory activity of methotrexate from an activated nanogel.

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Article ; Online: Studies on mefenamic acid microparticles: formulation, in vitro release, and in situ studies in rats.

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Article: Acceleration of in vitro dissolution studies of sustained release dosage form of theophylline and in vitro-in vivo evaluations in terms of correlations.

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