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Acyclovir-Loaded Chitosan Nanospheres from Nano-Emulsion Templating for the Topical Treatment of Herpesviruses Infections
(Mdpi, 2018) Donalisio, Manuela; Leone, Federica; Civra, Andrea; Spagnolo, Rita; Ozer, Ozgen; Lembo, David; Cavalli, Roberta
Acyclovir is not a good candidate for passive permeation since its polarity and solubility limit is partitioning into the stratum corneum. This work aims to develop a new topical formulation for the acyclovir delivery. New chitosan nanospheres (NS) were prepared by a modified nano-emulsion template method. Chitosan NS were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), and an in vitro release study. The in vitro skin permeation experiment was carried out using Franz cells and was equipped with porcine skin. Biological studies were performed on the Vero cell line infected by HSV-1 and HSV-2 strains. The acyclovir loaded chitosan NS appeared with a spherical shape, a size of about 200 nm, and a negative zeta potential of about 40.0 mV. The loading capacity of the drug was about 8.5%. In vitro release demonstrated that the percentage of acyclovir delivered from the nanospheres was approximately 30% after six hours. The in vitro skin permeation studies confirmed an improved amount of permeated acyclovir. The acyclovir-NS complex displayed a higher antiviral activity than that of free acyclovir against both the HSV-1 and the HSV-2 strain. The acyclovir-loaded NS showed no anti-proliferative activity and no signs of cytotoxicity induced by NS was detected. Confocal laser scanning microscopy confirmed that the NS are taken up by the cells.
Antioxidant properties evaluation of topical astaxanthin formulations as anti-aging products
(Wiley, 2019) Eren, Bilge; Tanriverdi, Sakine Tuncay; Kose, Fadime Aydin; Ozer, Ozgen
Background The reactive oxygen species lead to skin aging via oxidative damage that are induced by UV radiation. Therefore, topical formulations which have antioxidant effect could reduce aging level. Astaxanthin is an antioxidant substance. Aims The aim of this study was to investigate antioxidant activity and cytotoxicity potential of the astaxanthin-loaded gel formulations. Methods Astaxanthin-loaded oleoresin and algae extract were used as natural active materials. The lipogel and hydrogel of these natural materials were prepared as anti-aging formulations. The formulations were characterized via parameters such as, pH, rheological analysis, mechanical properties, and stability. And also in vitro release experiments of the formulations were carried out. The antioxidant activity and cytotoxicity test were performed. Results The results of characterization studies confirmed the formulations suitable for topical application. After 24 hours, 99 mu g, 88.3 mu g, 403 mu g, and 234.8 mu g of astaxanthin released through oleoresin lipogel, oleoresin hydrogel, algae extract lipogel, and algae extract hydrogel, respectively. It was found by the cytotoxicity tests that astaxanthin is more proliferative in lipogel formulations compared to hydrogel formulations. And finally, the highest antioxidant activity was found in the algae extract hydrogel and algae extract lipogel formulation, respectively (P < .05). Conclusions Topical formulations of astaxanthin-loaded oleoresin and algae extract were prepared successfully. At the same time, according to antioxidant activity and release studies, algae extract loaded could be suggested as topical anti-aging formulations.
Bio-based topical system for enhanced salicylic acid delivery: preparation and performance of gels
(Wiley, 2016) Langasco, Rita; Spada, Gianpiera; Tanriverdi, Sakine Tuncay; Rassu, Giovanna; Giunchedi, Paolo; Ozer, Ozgen; Gavini, Elisabetta
ObjectivesNew salicylic acid (SA)-loaded gels were developed using excipients made from renewable materials, and our goal was to improve drug permeation in the topical treatment of acne vulgaris. MethodsWe studied the preparation parameters to obtain suitable gel formulations. Only naturally occurring polymers were used as gelling agents. Two hydrogels and three lipogels were selected and characterized in terms of drug loading, pH, viability cells, rheology, mechanical properties and in vitro permeation; these hydrogels and lipogels were compared with the traditional ointment. We also evaluated skin parameters before and after gel application. Key findingsThe formulations that we studied are non-Newtonian fluids; they have high drug loading and suitable mechanical properties. Lipogels exhibit a slower and more linear in vitro permeation profile compared with hydrogels. The different vehicles that we used affected drug permeation and improve patient compliance. Cytotoxicity studies suggest that all of the formulations are non-toxic. ConclusionsLipogels demonstrate appropriate technological features and improved performance compared with the traditional ointment with regard to their composition. Lipogels may represent a new bio-based topical system for SA delivery. The use of green' excipients leads to skin-friendly' formulations that are able to satisfy environmental safety.
Combining dexamethasone and TNF-alpha siRNA within the same nanoparticles to enhance anti-inflammatory effect
(Elsevier, 2021) Gurcan, Serra; Tsapis, Nicolas; Reynaud, Franceline; Denis, Stephanie; Vergnaud, Juliette; Ozer, Ozgen; Fattal, Elias
We propose to combine two therapeutic anti-inflammatory approaches with different mechanisms of action in a single drug delivery system consisting of cationic dexamethasone palmitate nanoparticles (CDXP-NP) associated with TNF-alpha siRNA. The CDXP-NPs are obtained by the solvent emulsion evaporation technique using dexamethasone palmitate, a prodrug of dexamethasone, associated with a cationic lipid, DOTAP. Their physicochemical properties as well as their ability to bind siRNA were evaluated through gel electrophoresis and siRNA binding quantification. SiRNA cellular uptake was assessed by flow cytometry and confocal microscopy on RAW264.7 macrophages. TNF-alpha inhibition was determined on LPS-activated RAW264.7 macrophages. Stable and monodisperse nanoparticles around 100 nm with a positive zeta potential (+59 mV) were obtained with an encapsulation efficiency of the prodrug of 95%. A nitrogen/phosphate (N/P) ratio of 10 was selected that conferred the total binding of siRNA to the nanoparticles. Using these CDXP-siRNA-NPs, the siRNA was strongly internalized by RAW264.7 macrophage cells and localized within the cytoplasm. on the LPS-induced RAW264.7 macrophages, a larger inhibition of TNF-alpha was observed with CDXP-siRNA-NPs compared to CDXP-NPs alone. in conclusion, from these data, it is clear that a combination of DXP and TNF-alpha siRNA therapy could be a novel strategy and optimized alternative approach to cure inflammatory diseases.
Comparison of PLGA and lecithin/chitosan nanoparticles for dermal targeting of betamethasone valerate
(Informa Healthcare, 2013) Ozcan, Ipek; Azizoglu, Erkan; Senyigit, Taner; Ozyazici, Mine; Ozer, Ozgen
Poly(lactide-co-glycolide) (PLGA) and lecithin/chitosan (LC) nanoparticles were prepared to evaluate the difference in the behavior upon administration on skin, for steroidal treatment. For this purpose, betamethasone-17-valerate (BMV)-loaded nanoparticles with a narrow size distribution and high entrapment efficiency were prepared. Permeation studies showed that both polymeric nanoparticles enhanced the amount of BMV in epidermis, which is the target site of topical steroidal treatment, when compared with commercial formulation. 1.58-Fold increase was determined in the epidermis concentration of BMV by LC nanoparticles with respect to PLGA nanoparticles. Nanoparticles were diluted in chitosan gel (10%, w/w) to prepare suitable formulation for topical application. Accumulation from both gel formulations were found significantly higher than commercial formulation in skin layers (p<0.05). In addition, pharmacodynamic responses were also investigated as anti-inflammatory and skin-blanching parameters. Both formulations significantly improved these parameters although they contained 10 times less amount of BMV than commercial cream. Moreover, TEWL measurement exhibited no barrier function changes upon the application of nanoparticles on skin. Overall, both nanoparticles improved the localization of BMV within skin layers; but when compared with PLGA nanoparticles, the LC nanoparticles could be classified as a better candidate for topical delivery vehicle in the treatment of various dermatological inflammatory diseases.
Cosmeceuticals: Science to Practice
(Ortadogu Ad Pres & Publ Co, 2008) Ozer, Ozgen
The use of cosmeceuticals has significantly risen in recent years. They're topical cosmetic-pharmaceutical hybrids which contain ingredients that influence the skin's biological function. Cosmeceuticals have to be safe and meet consumer demands for high efficacy. In order to avoid undesired effects, the efficiency and possible reactions of skin care products composod of different ingredients must be tested and proven scientifically.
Deoxycholate hydrogels of betamethasone-17-valerate intended for topical use: In vitro and in vivo evaluation
(Elsevier Science Bv, 2011) Senyigit, Taner; Tekmen, Isil; Sonmez, Ulker; Santi, Patrizia; Ozer, Ozgen
The aim of this study was to evaluate the suitability of sodium-deoxycholate (Na-DOC) gels containing betamethasone-17-valerate (BMV) for topical application. The gels were characterized for rheological and textural properties. The in vitro flux of BMV from Na-DOC gels across rat skin was 2.5 (0.05% gel) and 8.5 times (0.1% gel) higher compared to the commercial cream (0.1%), respectively. The pharmacodynamic responses after in vivo topical application in rats were also determined. A significant correlation between anti-inflammatory activity and in vitro permeation of BMV was observed. Na-DOC gels produced significantly higher edema inhibition compared to commercial cream at all time intervals. Finally, according to the results of histology studies, Na-DOC gel has no irritant effect on the skin. In conclusion, Na-DOC gel formulation could be suggested as a promising alternative system for the topical application of BMV. (C) 2010 Elsevier B.V. All rights reserved.
Design and Evaluation of Topical Antioxidant Nanogel Formulations
(Soc Cosmetic Chemists, 2021) Tetik, Gokce; Rencber, Seda; Ozoglu, Ezgi T.; Yapar, Evren A.; Karavana, Sinem Y.; Ozer, Ozgen
Transdermal delivery of an active substance is promising, but a challenging option is available for local and systemic effects. The prolonged residence of formulation in the skin is important for topical delivery. in this study, it was aimed to develop a formulation that can overcome the stability and absorption problems of the vitamin C active substance by preparing nanogels. Nanogel-based materials have high drug loading capacity, biocompatibility, stability, and biodegradability, which are the key points to design a topical drug delivery system. Bovine serum albumin (BSA) and chitosan (CS) were used to prepare nanogels by a simple green self-assembly technique. Prepared nanogels were successfully used to entrap vitamin C, with an entrapment ratio between 86.08% +/- 1.29% and 107.93% +/- 1.04%. The studies started with vitamin C analysis and continued with characterization studies such as homogeneity, pH, viscosity, rheological properties, zeta potential, polydispersity index, particle size, and in vitro dissolution studies of nanogels. The antioxidant activities of the formulations were also tested by cell culture studies. The antioxidant activities of the nanogels were also tested by in vitro 2,2-diphenyl-1-picrylhydrazyl assay. Although topical vitamin C is effective in many ways, it has a risk of serious stability and absorption problems. The present work was aimed at developing pharmaceutically optimized topical nanogel formulations of vitamin C for antioxidant effect. An optimum nanogel formulation was composed of a 1:4 ratio of CS:BSA with (F19 formulation) in terms of entrapping vitamin C, formulation homogeneity, pH, viscosity, theological properties, zeta potential, PI, particle size, in vitro dissolution and cell culture studies. 'line optimized formulation showed higher antioxidant efficacy in vitro than vitamin C. in conclusion, prepared topical nanogel of vitamin C was stable and could be used with promising potential for topical application.
Design of polyethylene glycol-polyethylenimine nanocomplexes as non-viral carriers: mir-150 delivery to chronic myeloid leukemia cells
(Wiley, 2013) Avci, Cigir Biray; Ozcan, Ipek; Balci, Tugce; Ozer, Ozgen; Gunduz, Cumhur
MicroRNAs (miRNAs) are acknowledged as indispensable regulators relevant in many biological processes, and they have been pioneered as therapeutic targets for curing disease. miRNAs are single-stranded, small (19-22nt) regulatory non-coding RNAs whose deregulation of expression triggers human cancers, including leukemias, mainly through dysregulation of expression of leukemia genes. miRNAs can function as tumour suppressors (suppressing malignant potential) or oncogenes (activating malignant potential) like actors of complex diseases. To address the issue of overcoming instability and low transfection efficiency in vitro, the polyethylene glycol-polyethyleneimine (PEG-PEI) nanoparticle was used as non-viral vector carrier for miR-150 transfection, which is downregulated in chronic myeloid leukemia. PEG-PEI [PEG((550)3)-g-PEI(1800)]/miRNA nanocomplexes were synthesised and characterised by particle size distribution (PSD), polydispersity index (PDI) and zeta potential, surface charge, their cytotoxicity, and transfection efficiency. Interaction with human leukemia cells (K-562 and KU812) and control cells NCI-BL2347 with them has been investigated. The transfection efficiency of PEG-PEI/miRNA at N/P 26 rose 6.7-fold above the control by qRT-PCR. The size of homogenous nanocomplexes (PBI<0.5) was 160.8 +/- 11nm. The data indicate that PEG-PEI may be an encouraging non-viral carrier for altering miRNA expression in the treatment of chronic myeloid leukemia, with many advantages such as relatively high miRNA transfection efficiency and low cytotoxicity.
Design, optimization and characterization of novel topical formulations containing Triamcinolone Acetonide
(Elsevier, 2020) Sagiroglu, Ali Asram; Ozsoy, Yildiz; Ozer, Ozgen
Triamcinolone Acetonide (TA), a lipid-soluble molecule, is a synthetic glucocorticosteroid with anti-scarring, immunosuppressive and anti-inflammatory activity. the penetration of TA through the hypertrophic scar is challenging due to the scar tissue is thicker than the normal skin tissue. To overcome this problem, it was planned to prepare liposomal systems which are using for their penetration enhancer effect in topical use. So, in the present study, TA loaded liposome and liposomal film formulations were prepared and optimized to increase release and also stability. For the optimization of liposome formulations, response surface methodology (RSM) was used and the selected independent variables were the amounts of phospholipon 90g (PH) and cholesterol (CH). Encapsulation efficiency, particle size and zeta potential which were selected as dependent variables for liposome were found as 85.18% +/- 2.01%, 185.2 +/- 2.15 nm and -7.48 +/- 0.42 mV, respectively. By using optimum liposome formulation, liposomal film formulations were prepared. the percentage of PVA ad PG were chosen as independent variables of liposomal film formulation. the dependent variables of the liposomal film formulations which were thickness, puncture strength and puncture deformation values were found to be 0.24 +/- 0.02 mm, 5.53 +/- 2.43 N/mm(2) and 8.65% +/- 1.45%, respectively. Spherical and uniform shapes of liposomes were confirmed by electron microscopy. the in-vitro bioadhesion work value of the optimum lipo-somal film formulation indicated that the films provide sufficient adhesion on the skin. in vitro release studies showed that the release behavior of TA from the optimized formulations fitted well with the Higuchi kinetic model. Physical stability tests demonstrated that optimized liposome and liposomal film were convenient for storage at 5 +/- 3 degrees C for at least 90 days. in conclusion, optimized liposome and liposomal film formulations of TA could be offered as a promising strategy regarding their release, particle size, high encapsulation efficiency and stability for the treatment of hypertrophic scars.
Different approaches for improving skin accumulation of topical corticosteroids
(Elsevier Science Bv, 2009) Senyigit, Taner; Padula, Cristina; Ozer, Ozgen; Santi, Patrizia
The aim of this paper was to evaluate the effect of vehicle, chemical enhancer and iontophoresis on the skin accumulation of clobetasol propionate (CP) and mometasone furoate (MF). In vitro permeation experiments were performed using pig ear skin as barrier and HPLC as quantification method. The formulations tested were chitosan gels, sodium-deoxycholate gels and commercial creams of CP and ME The results obtained indicate that Na-DOC gel had an enhancing effect on the skin accumulation of both active agents. This effect was more evident with CP especially in the stratum corneum and epidermis which are the target sites of topical steroidal treatment. Two terpene derivatives (D-limonene and nerolidol) and Transcutol (R) P were evaluated as chemical penetration enhancers. Nerolidol produced considerable increase in the amount of CP and MF accumulated without any permeation across the skin. The application of electric current (anodal iontophoresis) to the gels improved the accumulation of MF while it did not effect the accumulation of CP. Due to the best accumulation results of nerolidol, the enhancement effect in combination with iontophoresis was also investigated. It was shown that, the combination of anodal iontophoresis and chemical enhancer (nerolidol) produced no further enhancement for both active agents. (C) 2009 Elsevier B.V. All rights reserved.
Different approaches for improving skin accumulation of topical corticosteroids
(Elsevier Science Bv, 2009) Senyigit, Taner; Padula, Cristina; Ozer, Ozgen; Santi, Patrizia
The aim of this paper was to evaluate the effect of vehicle, chemical enhancer and iontophoresis on the skin accumulation of clobetasol propionate (CP) and mometasone furoate (MF). In vitro permeation experiments were performed using pig ear skin as barrier and HPLC as quantification method. The formulations tested were chitosan gels, sodium-deoxycholate gels and commercial creams of CP and ME The results obtained indicate that Na-DOC gel had an enhancing effect on the skin accumulation of both active agents. This effect was more evident with CP especially in the stratum corneum and epidermis which are the target sites of topical steroidal treatment. Two terpene derivatives (D-limonene and nerolidol) and Transcutol (R) P were evaluated as chemical penetration enhancers. Nerolidol produced considerable increase in the amount of CP and MF accumulated without any permeation across the skin. The application of electric current (anodal iontophoresis) to the gels improved the accumulation of MF while it did not effect the accumulation of CP. Due to the best accumulation results of nerolidol, the enhancement effect in combination with iontophoresis was also investigated. It was shown that, the combination of anodal iontophoresis and chemical enhancer (nerolidol) produced no further enhancement for both active agents. (C) 2009 Elsevier B.V. All rights reserved.
Dual-Prevention for UV-Induced Skin Damage: Incorporation of Melatonin-Loaded Elastic Niosomes into Octyl Methoxycinnamate Pickering Emulsions
(Springer, 2017) Azizoglu, Gulcin Arslan; Tanriverdi, Sakine Tuncay; Kose, Fadime Aydin; Kirmizibayrak, Petek Ballar; Ozer, Ozgen
Incorporation of antioxidants into sunscreens is a logical approach, yet co-delivery of them with UV filters is a challenge. Here, we purposed a combination therapy, in which the chemical UV filter, octyl methoxycinnamate, was accumulated on upper skin while the antioxidant, melatonin, can penetrate deeper layers to show its effects. Melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion were prepared separately. Lyophilized elastic niosomes were dispersed into the Pickering emulsion to prepare the proposed combination formulation. The characterization studies of the formulations revealed that elastic niosomes can be prepared with tunable nanometer sizes, whereas Pickering emulsions can encapsulate the UV filter in micrometer-sized droplets. Melatonin-loaded elastic niosomes prepared with Tween80/Span80 mixture were 146 nm with a PI of 0.438, and 58.42% entrapment efficiency was achieved. The mean diameter size of the combination formulation was 27.8 mu m. Ex vivo permeation studies revealed that 7.40% of octyl methoxycinnamate and 58% of melatonin were permeated through the rat skin while 27.6% octyl methoxycinnamate and 37% of melatonin accumulated in the skin after 24 h. Cell culture studies with real-time cell analyzer showed that the proposed formulation consist of melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion had no negative effect on the cell proliferation and viability. According to alpha,alpha-diphenyl-beta-picrylhydrazyl free radical scavenging method, the proposed formulation showed as high antioxidant activity as melatonin itself. It is concluded that the proposed formulation would be a promising dual therapy for UV-induced skin damage with co-delivery strategy.
Effective topical delivery systems for corticosteroids: dermatological and histological evaluations
(Taylor & Francis Ltd, 2016) Eroglu, Ipek; Azizoglu, Erkan; Ozyazici, Mine; Nenni, Merve; Orhan, Hande Gurer; Ozbal, Seda; Tekmen, Isil; Ertam, Ilgen; Unal, Idil; Ozer, Ozgen
Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220-350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (similar to 13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.
EFFECTS OF STERILIZATION TECHNIQUES ON INJECTABLE STEALTH BONE TARGETED NANOPARTICLES
(Elsevier Science Bv, 2009) Ozcan, Ipek; Sanchez, Freimar Segura; Bouchema, Kawthar, I; Abaci, Ozlem; Ozer, Ozgen; Guneri, Tamer; Ponchel, Gilles
EFFECTS OF STERILIZATION TECHNIQUES ON INJECTABLE STEALTH BONE TARGETED NANOPARTICLES
(Elsevier Science Bv, 2009) Ozcan, Ipek; Sanchez, Freimar Segura; Bouchema, Kawthar, I; Abaci, Ozlem; Ozer, Ozgen; Guneri, Tamer; Ponchel, Gilles
Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations
(Dove Medical Press Ltd, 2013) Ozcan, Ipek; Azizoglu, Erkan; Senyigit, Taner; Ozyazici, Mine; Ozer, Ozgen
The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.
Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations
(Dove Medical Press Ltd, 2013) Ozcan, Ipek; Azizoglu, Erkan; Senyigit, Taner; Ozyazici, Mine; Ozer, Ozgen
The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.
Establishment and Validation of an Automated System for the Antifactor IIa Assay: A Case Study of Potency Assessment of a Pharmaceutical Gel Formulation
(Amer Chemical Soc, 2024) Ozgen, Gokselin; Turk Gezer, Merve; Armagan, Guliz; Kirmizibayrak, Petek Ballar; Yalcin, Ayfer; Ozer, Ozgen; Arslan, Banu Ozkirim
Antithrombotic agents and anticoagulant drugs, such as those from the heparin family, are employed in clinical settings for the prevention and treatment of clotting, thromboembolism, and wound healing. The potency assessment of antithrombotic agents is typically conducted using antifactor IIa assay with manual systems which are time-consuming and often lack repeatability. Here, we present a novel automated system that significantly enhances assay repeatability, attaining an outstandingly low relative standard deviation (RSD) % of only 0.6% for repeatability. This system has been applied to a pharmaceutical gel formulation for wound healing developed by Abdi Ibrahim Pharmaceuticals R&D Center as a case study for validation. The automated system demonstrated substantial improvements over manual systems in linearity (R-2 = 0.9927), precision, accuracy, specificity, and robustness. The system aligns with the European Pharmacopoeia specifications, promising to enhance quality control across pharmaceutical formulations and conduct absorbance-based end-point assays within the pharmaceutical industry while offering increased throughput and cost-effectiveness.
Evaluation of characteristics and in vitro antioxidant properties of RSV loaded hyaluronic acid-DPPC microparticles as a wound healing system
(Elsevier Science Bv, 2015) Eroglu, Ipek; Gokce, Evren H.; Tsapis, Nicolas; Tanriverdi, Sakine Tuncay; Gokce, Goksel; Fattal, Elias; Ozer, Ozgen
Resveratrol (RSV) was incorporated into microparticles by spray drying to treat chronic wounds such as diabetic ulcers. RSV was chosen due to its defense mechanisms as the formation of free radicals delays the healing process. RSV was loaded into microparticles consisting of dipalmitoylphosphatidylcholine (DPPC) and hyaluronic acid (HA), a polysaccharide naturally present within the skin, known to contribute to the healing process. Microparticles were evaluated in terms of production yield, size distribution, encapsulation efficiency, morphology, specific surface area, thermal properties and water content. Spherical and homogenous microparticles (span <= 2) in a size range between 20 and 30 mu m were obtained with high encapsulation efficiency (>= 97%). The effect of enzymes (hyaluronidase, phospholipase and lipase) on RSV release showed a dose-dependent pattern followed by a slow release stage. Cytotoxicity/proliferation and oxidative stress parameters (glutathione, oxidized glutathione, glutathione peroxidase, malondialdehyde, superoxide dismutase) obtained from human dermal fibroblast cell cultures revealed that formulations increased cell proliferation and the presence of RSV decreased oxidation in cells. RSV-loaded HA-DPPC microparticles appear as a promising formulation for wound healing due to synergistic effect of the ingredients. (C) 2014 Elsevier B.V. All rights reserved.

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