Management of bacterial infections by advanced drug delivery systems /
علاج العدوى البكتيرية من خلال استخدام أنظمة توصيل دوائية متطورة
by Alaa Subhi Mahmoud Eita ; Supervision Prof. Dr. Amna Mohamad AwadAllah Makky, Prof. Dr. Islam Ahmed Hamed Khalil.
- 146 pages : illustrations ; 25 cm. + CD.
Thesis (Ph.D) -Cairo University, 2025.
Bibliography: pages 126-146.
Amlodipine, a well-known antihypertensive agent, has shown promising antibacterial potential, particularly against resistant bacterial strains. Utilizing nanoparticle-based delivery systems enhances the therapeutic performance by improving drug stability, bioavailability, and controlled release. The development of an optimized formulation is critical to achieving maximum antibacterial efficacy and efficient delivery. The nanotechnological approach highlights the potential of drug repurposing combined with formulation optimization as an effective strategy to overcome antimicrobial resistance and improve therapeutic outcomes. The thesis is organized into two chapters: Chapter 1: Repurposing amlodipine as an antibacterial topical formulation for skin infection. This study investigates the antibacterial potential of amlodipine (AML) by formulating it into Pluroleosomes (PLOs), lipid-based vesicles composed of soya lecithin, oleic acid, and Pluronic F-127, designed to enhance drug solubility, skin penetration, and topical delivery efficiency. A D-optimal mixture design was employed to optimize formulation variables and identify the most effective composition that achieves favorable particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized AML-PLO formulation was incorporated into a foam system to facilitate uniform application and improve dermal permeation. Characterization studies confirmed the nanoscale, spherical morphology and chemical compatibility of the formulation components. The AML-PLOs foam formulation exhibited sustained drug release and effective penetration through skin layers. Both in-vitro antibacterial assays and in-vivo wound healing studies demonstrated significant antibacterial efficacy against MRSA, supporting the potential of the optimized AML-PLO foam as a novel and effective nanocarrier system for the topical treatment of bacterial infections and as a promising example of drug repurposing through formulation optimization. Chapter 2: Repurposing amlodipine as an antibacterial topical formulation for ocular infection. This study investigates the antibacterial potential of amlodipine (AML) through its incorporation into polymeric zein nanoparticles (AML-ZNs) designed to enhance ocular drug delivery and overcome physiological barriers. A Box–Behnken design was employed using Design-Expert® software to optimize formulation parameters, including zein, Labrafac, and Poloxamer 407 concentrations, to achieve minimum particle size and polydispersity with maximum zeta potential and entrapment efficiency. The optimized AML-ZNs formulation was subsequently coated with sodium alginate to improve system stability, control drug release, and adjust viscosity for practical use as eyedrops. Characterization confirmed the presence of uniform nanospherical particles with favorable physicochemical properties and sustained release behavior. The alginate-coated formulation exhibited controlled drug release, enhanced ocular penetration, and maintained stability and sterility. In-vitro antibacterial assays and in-vivo ocular studies demonstrated the potent antibacterial activity of amlodipine against MRSA, supporting its potential repurposing as an effective antimicrobial agent. Overall, the optimized AML-ZNs–Alg system presents a promising nanocarrier platform for safe and efficient ocular drug delivery in the treatment of bacterial infections يُعد الانتشار المرتفع للسلالات البكتيرية المقاومة من أبرز التحديات في علاج العدوى البكتيرية. وقد أدى تصاعد مقاومة الميكروبات للمضادات الحيوية التقليدية إلى ضرورة إجراء أبحاث مستمرة تهدف إلى اكتشاف استراتيجيات مبتكرة أو كيانات كيميائية جديدة قادرة على التغلب على هذه السلالات المقاومة. يُعتبر اكتشاف كيان كيميائي جديد ذي فعالية مضادة للبكتيريا أمرًا معقدًا، ويتطلب جهدًا كبيرًا واستثمارًا ماليًا ضخمًا. لذلك، أصبح الاعتماد على إعادة توظيف الأدوية خيارًا متزايدًا للسيطرة على مقاومة البكتيريا، من خلال تحديد أدوية بديلة ذات خصائص مضادة للبكتيريا مكتشفة حديثًا. وقد أظهرت عدة فئات علاجية فعالية ضد السلالات المقاومة، بما في ذلك المكورات العنقودية الذهبية المقاومة للميثيسيلين (MRSA)، مثل مضادات الالتهاب غير الستيرويدية، وأدوية الروماتيزم، ومضادات الاكتئاب، ومضادات الطفيليات، وأدوية السكري. ويُفضل استخدام أنظمة النواقل النانوية بالتوازي مع استراتيجية إعادة التوظيف لتعزيز النفاذية، وتنظيم إطلاق الدواء، وضمان أقصى فعالية علاجية.
Text in English and abstract in Arabic & English.
Pharmaceutics الصيدلانيات
amlodipine repurposing pluroleosomes zein foam eye drops bacterial infection MRSA أملوديبين إعادة توظيف