الفهرس 
AbstractOnly 14 pages are availabe for public view
 |  | from | 189 |  |  |
| | | from | 189 | | |
Abstract
Bioidentical Progesterone (PRG) Is An Exogenous Female Steroidal Hormone, Which Is Identical To The Endogenous PRG In Structure. It Does Not Give Any Androgenic Action That May Induce Teratogenicity Or Affects Lipoprotein Metabolism. PRG Is Used In The Treatment Of Different Female Reproductive Conditions. However, It Has A Major Problem Which Is The Low Bioavailability Due To Extensive Hepatic Metabolism And Poor Solubility. Avoiding The Oral Route Will Help Reduce Potential Extensive Hepatic Metabolism And Hence Improve Patient Compliance And Treatment Success. Among The Numerous Non-Oral Routes Of Drug Administration Such As Transdermal And Vaginal Routes Seem To Be More Advantageous And A Potentially Useful Route Of PRG Administration. Nano Vesicle Transethosomes (Nvtes) Are A Novel Approach Permeation –Enhancing Lipid Nanovesicular System That Is Derived from Transferosomes And Ethosomes That Were Encompassing Their Advantages. Thus Nvtes Were Developed To Enhance PRG Permeation Across Skin And Vaginal Mucosa, Distribution, Controlled Release characteristics And Specific Uterine Targeting.
Aim: To Evaluate And Statistically Optimize PRG-Loaded Nanovesicle Transethosomes (Nvtes) That Were Prepared By Injection Sonication Method. A 24 Full Factorial Design Was Used To Explore The Effect Of Phosphatidylcholine (PC), Tween 80, Cetyltrimethyl Ammonium Bromide And Ethanol Concentration On Particle Size, Entrapment Efficiency (EE %), % In Vitro PRG Release After 24h And Flux. The Results Revealed That The Mean Particle Sizes Ranged from 133.3 ± 3.42 To 349.5 ± 1.24 Nm, EE % Ranged from 87.93±3.58 To 97.05 ± 2.61%, % PRG Release Ranged from 48.49 ± 1.54 To 85.69 ± 2.23 For Ph7.4 And At Ph4.5 Ranged from 87.93 ± 3.58 To 97.05 ± 2.61%, Zeta Potential Ranged from -23.5±3.84 To +74.6±4.97mv. The Optimized Nvtes Formulation Was Subjected To Transmission Electron Microscope For Morphological Examination.
Specific Objectives (1): To Develop Hydrogel Uploaded With The Optimized Nvtes Formulation For Transdermal Application Using Carbopol 974, Hydroxyl Propyl Methylcellulose (CAP/HPMCH15) Combination As Gel Base. The Optimized CAP/HPMC Hydrogel Containing Optimized PRG-Loaded Nvtes Was Subjected To Further In-Vivo Investigations And Compared To The PRG Suspension And Control Gel. The Pharmacokinetic Study Of PRG –Loaded Nvtes Transdermal Hydrogel In Male Rats Showed A Markedly Increase In Bioavailability When Compared With The Drug Suspension And Control Gel.
(2): The Purpose Of This Study Was To Prepare And Statistically Optimize PRG-Loaded Nvtes Mucoadhesive Gel For Vaginal Delivery Using CAP 974, HPMCH15 And Sodium Alginate (SA) Combinations As Mucoadhesive Gel Base. Box-Behnken Design Was Employed To Investigate The Joint Effect Of Independent Variables; CAP 974, HPMC H15 And SA Concentration On Mucoadhesion, %PRG Release And Ph. The F16 Was Chosen As The Optimized Formulation With Highest Release, Maximum Mucoadhesion And PH In Target To 4.5 For Mimic Vaginal PH. The Optimized Formulation Was Clinically Studied In Anovulatory Polycystic Ovary Syndrome (PCOS). The Study Was Carried Out On 60 Anovulatory Patients That Randomly Allocated To Two Groups where Each group Was Assessed By Ultrasound Scanning Of The Endometrium, Endometrial Thickness, Width, Echogenicity Degree And The Serum PRG That Was Measured By ELISA Then The Pregnancy Rate Was Calculated. Clinical Study Showed A Significant Increase In The Serum PRG, Endometrial Thickness, Echogenicity Degree And The Pregnancy Rate.
Conclusion: PRG –Loaded Nvtes Hydrogel Seems To Be Promising Novel Formulation That Has Higher Permeability And Enhanced Systemic Bioavailability. The Vaginal Gel Uploaded With PRG-Loaded Nvtes Might Be A Promising Formulation For Luteal Phase Support And Increase Pregnancy Rate In Anovulatory PCOS.