1.A nanometer lipid emulsion, lipid nano-sphere (LNS), as a parenteral drug carrier for passive drug targeting.
Seki J1, Sonoke S, Saheki A, Fukui H, Sasaki H, Mayumi T. Int J Pharm. 2004 Apr 1;273(1-2):75-83.
We attempted to develop an artificial lipoprotein-like particle, lipid nano-sphere (LNS), incorporating dexamethasone palmitate (DMP). LNS is 25-50 nm in diameter and is composed of soybean oil and egg lecithin. Potential drug carriers were compared with a conventional fat emulsion for intravenous nutrition, lipid microsphere (LM, d=200-300 nm), which is already used clinically. LM easily entered reticuloendothelial systems, such as the liver, and was rapidly cleared from the circulation. However, LNS showed much higher plasma levels of DMP after intravenous administration to rats and recovered more than 80% of the injected dose in the perfusate in single-pass rat liver perfusion. The calculated volume for the distribution of the lipid emulsion within the liver showed that LNS underwent fenestration and was distributed into the Disse space in the liver. Because of the lower uptake of LNS particles by the liver, LNS showed good recovery from the liver and prolonged the plasma half-life of DMP after intravenous injection.
2.Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation: macrophage-targeted steroid therapy.
Nishiwaki S1, Nakayama T, Murata M, Nishida T, Sugimoto K, Saito S, Kato T, Mizuno H, Imahashi N, Seto A, Ozawa Y, Goto T, Koyama D, Yokohata E, Kubota N, Kamoshita S, Miyamura K, Matsumoto K, Ito M, Naoe T. Int J Hematol. 2012 Apr;95(4):428-33. doi: 10.1007/s12185-012-1023-z. Epub 2012 Feb 15.
Hemophagocytic syndrome (HPS) induced by uncontrolled macrophage activation and subsequent graft failure is a frequent and prominent complication after allogeneic stem cell transplantation (allo-SCT), a cause of severe morbidity and death, and a therapeutic challenge. Liposome-incorporated dexamethasone, dexamethasone palmitate (DP), shows greater efficacy against macrophages as compared to dexamethasone sodium phosphate (DSP). Based on our findings that DP achieves significantly larger decrease than DSP on the viability of primary human macrophages compared in vitro, we tested the effects of DP in patients with HPS. A decrease in number of macrophages in the bone marrow and prevention of engraftment failure were observed in all patients without any severe complications. In conclusion, these data provide a rationale for testing DP as a first-line treatment for patients with HPS after allo-SCT.
3.Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis.
Doi T1, Ohga S, Ishimura M, Takada H, Ishii K, Ihara K, Nagai H, Hara T. Eur J Pediatr. 2013 Nov;172(11):1475-81. doi: 10.1007/s00431-013-2065-9. Epub 2013 Jun 29.
Control of refractory bleeding in idiopathic pulmonary hemosiderosis (IPH) is challenging. Based on the effect of liposteroid (dexamethasone palmitate) for acute bleeding in two reported cases, the long-term utility was assessed in all nine IPH children (including the first two cases) treated in a tertiary center for 20 years. The median at disease onset was 2.3 years (range, 1.2 to 8.6). All had life-threatening and/or repetitive bleeding on prednisolone (PSL) therapy. Liposteroid was intravenously infused at 0.8 mg/kg/day for three consecutive days at the time of acute bleeding. Single infusion was followed by a longer interval from weekly to monthly accompanied by low-dose PSL (less than 0.3 mg/kg/day). Monthly infusion as maintenance therapy was continued for prophylaxis of bleeding. Treatment outcomes were retrospectively analyzed. During the observation period of a median of 11.0 years (range 2.4-16.9 years), no one died. Five patients were weaned and the other one was being weaned from liposteroid for the cure or long remission (median, 5.
4.Successful treatment with liposteroid followed by reduced intensity stem cell transplantation in an infant with perforin deficiency presenting with hemophagocytic lymphohistiocytosis.
Kobayashi Y1, Salih HM, Kajiume T, Nakamura K, Miyagawa S, Sato T, Nishimura S, Kobayashi M. J Pediatr Hematol Oncol. 2007 Mar;29(3):178-82.
Perforin deficiency characterized by markedly reduced cytotoxic T and natural killer cell activities is one type of familial hemophagocytic lymphohistiocytosis (FHL). FHL is a fatal inherited disease, and treatment with stem cell transplantation has resulted in a normal activity of killer cells. We herein report a case of FHL with perforin deficiency that was primarily treated by the administration of liposteroid to reduce hypercytokinemia. Thereafter, allogenic bone marrow transplantation with nonmyeloablative conditioning was successfully performed without any adverse effects on the patient's physical or developmental status. These observations suggest that this treatment strategy might thus be recommended in infants with FHL to reduce treatment-related complications, especially in patients with relatively mild clinical courses.