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_222 _a620.5 _bE.M.D |
| 100 | 1 |
_aElgendy, Mohamed Ahmed Emad Abdellatif _eauthor. |
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| 245 | 1 | 0 |
_aDevelopment and Optimization of Liquid Crystalline Nanostructures for Enhanced Ocular Delivery / _cby Mohamed Ahmed Emad Abdellatif Elgendy Assistant Lecturer at Department of Pharmaceutics and Pharmaceutical Technology Faculty of Pharmacy, Future University in Egypt ; supervisors : Prof. Dr. Nahed Daoud Mortada Professor of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University, Prof. Dr. Mona Ibrahim Abdul Tawab Elassal Professor of Pharmaceutics and Pharmaceutical Technology Faculty of Pharmacy, Future University in Egypt, Prof. Dr. Rania Aziz Helmy Ishak Professor of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University, Dr. Mai Mansour Soliman Lecturer of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University. |
| 246 | 3 | 5 | _aتطوير وتعظيم بلورات سائلة نانووية لتحسين التوصيل الدوائي للعين |
| 264 | 0 | _c2022 | |
| 300 |
_a231 pages : _billustrations ; _c24 cm |
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| 336 |
_2rdacontent _atext _btxt |
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_2rdamedia _aunmediated _bn |
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| 338 |
_2rdacarrier _avolume _bnc |
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| 500 | _asupervisors : Prof. Dr. Nahed Daoud Mortada Professor of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University, Prof. Dr. Mona Ibrahim Abdul Tawab Elassal Professor of Pharmaceutics and Pharmaceutical Technology Faculty of Pharmacy, Future University in Egypt, Prof. Dr. Rania Aziz Helmy Ishak Professor of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University, Dr. Mai Mansour Soliman Lecturer of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University. | ||
| 502 | _aThesis (Ph.D.)--Ain Shams University, Faculty of pharmacy, Department of Pharmaceutics and Industrial Pharmacy,2022. | ||
| 504 | _aIncludes bibliographical references (pages 197- 231). | ||
| 520 | 3 | _aLiquid crystalline nanostructures (LCNs), for instance cubosomes, have been widely used as a promising carrier for drug delivery through the last few years. To date, the ophthalmic application of these platforms is not well explored, and the effect of integrating penetration enhancers (PEs) into LCNs has not been investigated yet. Cubosomes mainly prepared using Glyceryl monooleate (GMO) or Phytantriol (PYT) as a lipid with the addition of Poloxamer 407 (P407) as a stabilizer. The integration of new stabilizers other than P407 is still limited in research. Thus, this thesis is divided into three chapters. LCNs were prepared using hot emulsification method by coupling of novel PEs at different amounts into GMO-based cubosomes for ocular administration. The morphology of the formed LCNs was investigated using transmission electron microscopy (TEM). The crystallinity and thermal behavior studies were also conducted. The acceptable formulations exhibited relatively homogenous particle nano-sizes ranging from 139.26 ± 3.68 to 590.56 ± 24.86 nm carrying negative surface charges. TEM images, X-ray patterns and DSC thermograms demonstrated the influential effect of PEs in developing altered crystalline structures. Hen’s egg test-chorioallantoic membrane (HET-CAM), rabbit eye Draize test, and histopathological examinations of ocular tissues confirmed the ocular compatibility of optimized LCNs. The corneal distribution using confocal laser scanning microscope (CLSM) proved the disseminated fluorescence intensity of LCNs enriched with oleic acid, Captex® 8000 and Capmul® MCM as enhancers. Selected LCNs showed good physical stability upon storage and lyophilization. Moreover, D-optimal design was applied to investigate the optimal LCNs composition for drug loading. A preliminary study was conducted to optimize the key formulation components of LCNs; Phytantriol (PYT) in comparison to GMO as lipids, and different stabilizers were compared to P407. This study aimed to set the type and the amount range of each component to be used later in the experimental design for optimization, where GMO, TPGS and Tween 80 were proven to be the most suitable for fabrication of optimized LCNs loaded with the anti-glaucomic drug, Travoprost (TRAVO). Optimum formulae were F-1-L and F-3-L both composed of 25 mg GMO (lipid), 25 mg Tween 80 (stabilizer) and 25 mg of oleic acid and Captex 8000 (PE), respectively. They showed PS of 216.20 ± 6.12 and 129.40 ± 11.73 nm with PDI values of 0.27 ± 0.03 and 0.34 ± 0.03, respectively. The ZP values were -72.93 ± 1.97 and -17.55 ± 2.10 mV, and both formulae revealed high EE % of 85.30 ± 4.29 and 82.54 ± 7.65%, respectively. Furthermore, they showed the highest drug permeation profile during the ex-vivo studies. The pharmacodynamic (PD) and pharmacokinetic (PK) studies conducted on adult New Zealand White rabbits in addition to ocular tolerability and histological examinations showed that, F-1-L has achieved its lowest IOP (15.6 mmHg) at 6 h post-dose application and maintained its lowering effect for 48 h. On other hand, F3-L, showed the lowest IOP (13.9 mmHg) at 24 h after instillation and its effect lasted for the 72 h. At last, Travatan® (the market product) showed its lowest IOP (14.7 mm Hg) at 8 h and its effect was lasted for 36 h only. The LCN formula F-3- L showed a significant higher Cmax of 1.80 ± 0.15 ng/ml (p<0.05), when compared to 1.46 ± 0.06 and 1.42 ± 0.09 ng/ml obtained in case of F-1-L and Travatan®, respectively. The highest median Tmax of 6 h attained by F-3-L confirmed the more controlled drug permeation behavior than those achieved by Travatan® and F-1-L recording 1 and 2 h, respectively. Furthermore, the chosen formulation F-3-L showed significant higher AUC0-48, AUCinf and MRT of 62.77 ± 2.73 ng.h/ml, 406.69 ± 17.12 ng.h/ml and 23.18 ± 0.57 h in comparison to the respective data obtained from F-1-L and Travatan® 43.02 ± 2.97 and 11.58 ± 0.23 ng.h/ml, 133.63 ± 11.54 and 125.98 ± 8.54 ng.h/ml, 11.73 ± 0.22 and 11.58 ± 0.23 h. The bioavailability of both formulae relative to the market product TRAVATAN® was also calculated, as F-1-L showed a relative bioavailability of 106.1%, while F-3-L showed a much higher value of 322.82% with respect to the market product. All the tested LCNs did not show any signs of ocular damage or clinical abnormalities compared to the control eye as observed. The current thesis described the successful incorporation of a novel PE (Captex®8000) into conventional LCNs. Furthermore, TRAVO loading in such liquid crystals stabilized with Tween 80 resulted in a safe and effective ocular drug delivery system for glaucoma treatment. The prepared LCNs demonstrated favorable penetration power throughout the corneal layer, as well as good stability and high TRAVO entrapment efficiency. While instilling the same drug dose, the bioavailability of TRAVO was increased three-folds when delivered using LCNs relative to the market product Travatan®, confirming the superiority of the tailored TRAVO-LCNs in the management of glaucoma. | |
| 546 | _aText in English, abstract in English and Arabic. | ||
| 650 | 0 | _aNanostructures. | |
| 650 | 0 | _aNanotechnology. | |
| 650 | 0 |
_aNanostructures _xIndustrial applications. |
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| 700 | 1 |
_aMortada, Nahed Daoud _933955 _esupervisor |
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| 700 | 1 |
_aElassal, Mona Ibrahim Abdul Tawab _933956 _esupervisor |
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| 700 | 1 |
_aIshak, Rania Aziz Helmy _933957 _esupervisor |
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| 700 | 1 |
_aSoliman, Mai Mansour _933958 _esupervisor |
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| 856 | 4 | 0 | _uhttp://repository.fue.edu.eg/xmlui/handle/123456789/6059 |
| 942 | _cTHESIS | ||