The use of PEGylated liposomes in the development of drug delivery applications for the treatment of hemophilia

Abstract

Hemophilia A is a rare X-linked bleeding disorder caused by lack or dysfunction of coagulation factor VIII (FVIII). Hemophilia A is treated with replacement therapy, but frequent injections of the missing FVIII often lead to the formation of inhibitory antibodies. Patients who develop high levels of inhibitors must be treated with bypassing agents such as activated FVII (FVIIa). Both FVIII and FVIIa have short half-lives and require multiple injections. Long-acting forms of these proteins would therefore reduce the frequency of injections, improve patient compliance and reduce complications. In this article we present a new platform technology that produces long-acting forms of FVIII and FVIIa and improves the efficacy of hemophilia treatment. This technology is based on the binding of proteins/peptides to the outer surface of PEGylated liposomes (PEGLip). Binding is dependent on an amino acid consensus sequence within the proteins and is highly specific. At the same time, binding is non-covalent and does not require any modification of the therapeutic agent or its production process. Association of proteins with PEGLip results in substantial enhancements in their pharmacodynamic properties following administration. These improvements seem to arise from the association of formulated proteins with platelets prior to induction of coagulation.

Lipid-engineered nanotherapeutics for cancer management

“…Polyethylene glycol (PEG), a small polymer, stabilizes a liposome when added to its formulation because it creates steric hindrance against the interaction of the liposomal lipid layers with plasma proteins. A variety of PEG-based liposomal formulations have been used in various applications, ( Yatuv et al, 2010 ; Mohamed et al, 2019 ), with the most common being combinations of PEG with functional phospholipids such as 1,2-distearoylsn-glycero-3-phosphoethanolamine (DSPE). Chitosan, a naturally-derived polymer, has also been utilized to improve the stability of liposomes, and can be incorporated into liposomes using ionic interactions between the negatively charged liposomal surface and the positively charged hydrophilic chitosan.…”

New approaches to the diagnosis and treatment of coagulation disorders

“…К ним можно отнести удлинение времени жизни препарата в организме. Это достигается пришивкой факторов к липосомам, модифицированным полиэтиленгликолем [20], что позволяет удвоить время действия препарата. Однако иногда терапия липосомными препаратами может сопровождаться увеличением частоты дыхания и приливов крови [21,22].…”