Rheumatoid Arthritis: Naparstek Y

Avnir Y, Ulmansky R, Wasserman V, Even-Chen S, Broyer M, Barenholz Y, Naparstek Y. · The Hebrew University-Hadassah Medical School, Jerusalem, Israel. · Arthritis Rheum. · Pubmed #18163482 links to  free full text

Abstract: OBJECTIVE: The use of glucocorticoids (GCs) in rheumatoid arthritis is limited by side effects related to unfavorable pharmacokinetics and biodistribution. Liposomal GC formulations have been studied since the 1970s in an attempt to overcome this obstacle, but none has entered clinical use. We undertook this study to determine whether a novel approach could overcome the limitations that have thus far prevented the clinical use of these formulations: low drug:lipid ratio, low encapsulation efficiency, and lack of controlled release. METHODS: We used approximately 80-nm sterically stabilized (pegylated) nanoliposomes (NSSLs), which were remote-loaded with an amphipathic weak acid GC (such as methyl prednisolone hemisuccinate) utilizing an intraliposome (aqueous compartment)-high/extraliposome (bulk medium)-low transmembrane calcium acetate gradient. This unique method actually "traps" the GC in the liposomal aqueous phase as a calcium-GC precipitate. RESULTS: Our liposome formulation exhibited high encapsulation efficiency (94%) and a high drug:lipid mole ratio (0.41) and demonstrated controlled release of the encapsulated GC during systemic circulation and in inflamed paws in rats with adjuvant-induced arthritis. In addition, both in arthritic rats and in a Beagle dog, we showed the pharmacokinetic advantage of using liposomes as GC carriers. Finally, we demonstrated the superior therapeutic efficacy of our liposome formulation over that of free GCs in arthritic rats, both in early and in peak disease stages. CONCLUSION: Amphipathic weak acid GCs remote-loaded into approximately 80-nm NSSLs overcome past limitations of liposomal GC formulations. The unique loading method, which also leads to controlled release, improves the therapeutic effect both systemically and locally. Such a development has great potential for improving GC therapy.

Elinav H, Maly A, Ilan Y, Rubinow A, Naparstek Y, Amital H. · Department of Medicine "A," Institute of Pathology, Hadassah-Hebrew University School of Medicine, Ein-Karem, Jerusalem 91120, Israel. · J Am Acad Dermatol. · Pubmed #15097938 No free full text.

Abstract: Sweet's syndrome has a wide range of clinical manifestations. It may appear as a solitary cutaneous disorder but often it is associated with systemic signs and symptoms. This disorder might be idiopathic but it often is paraneoplastic or associated with medications or autoimmune diseases. In its systemic manifestation Sweet's disease resembles adult-onset Still's disease in many aspects. We present a case of a young man in whom Sweet's syndrome and Still's disease developed. Although the diagnosis of adult-onset Still's disease is made by exclusion, he fulfilled all the criteria of both conditions. Considering the clinical similarities of these diseases, it may be presumed that similar patients may have been overlooked in the past.