Liposomal factor VIII as an efficient pharmaceutical system for the treatment of hemophilia
- سال انتشار: 1403
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 27، شماره: 6
- کد COI اختصاصی: JR_IJBMS-27-6_011
- زبان مقاله: انگلیسی
- تعداد مشاهده: 225
نویسندگان
Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
چکیده
Objective(s): Currently, the most important treatment approach for hemophilia type A is recombinant Factor VIII. However, due to its low retention time in the blood, the patients usually need successive injections. In addition, neutralization of injected proteins by antibodies complicates treatment. We examined the prolongation of the persistence time of injectable FVIII in the blood and the potential effects on survival using promising PEGylated liposomes (PEGLip) utilizing hydrogenated soy phosphatidylcholine (HSPC, Tm= ۵۴.۵ ºC) and ۱-palmitoyl-۲-oleoyl-phosphatidylcholine (POPC, Tm= – ۲ ºC).Materials and Methods: Nanoliposomes with different percentages of PEG (۳% and ۵%) were obtained via the thin film hydration procedure and extrusion. Liposomal FVIII formulation was prepared and characterization was done.Results: The results revealed that the formulations are in the ۸۰–۱۲۰ nm range with uniform dispersion, which was confirmed using transmission electron microscopy (TEM) imaging. The phase transition temperature (Tm) of the liposomes was obtained by differential scanning calorimetry (DSC). With an attachment efficacy of approximately ۸۷%, proteins bind non-covalently yet with a strong affinity to the exterior of PEGLip. The final formulations underwent additional examination. No significant change was observed in size, charge, and PDI between the FVIII-conjugated liposomal formulations and their liposomal nanoparticles. The selected formulations were injected into BALB/c mice. The circulation time and potential clotting effectiveness of PEGLip-FVIII are vastly improved over free protein, in non-hemophilic mice. Conclusion: The obtained results showed that using phospholipids with high Tm (HSPC) can improve the hemostatic efficiency of liposomes more than phospholipids with low Tm (POPC).کلیدواژه ها
Antihemophilic factor, Hemophilia A, PEGylated liposomes, Recombinant FVIII, Haemophilia therapyاطلاعات بیشتر در مورد COI
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