Solutol HS-15 , a clinically approved excipient, has neuroprotective properties[1,2]. Solutol HS 15 (polyoxyethylene esters of 12-hydroxystearic acid) is non-ionic surfactant, with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells[3]. Solutol HS-15 also acts as a permeability enhancer[4].
Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively,at a concentration of 10% of its own IC50 (mean concentration of drug that causes 50% inhibition of cell growth compared to controls). Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific.
Solutol HS 15 is a third generation surfactant carrier used to improve the solubility and bioavailability [5,6]. Solutol HS 15 was the most effective to increase the solubility of Pioglitazone HCl by approximately 33 fold whereas Cremophor RH 40 increased approximately 27 folds. Suitability of Solutol HS 15 has earlier been demonstrated with its physiological compatibility and safety [7].There was simultaneous increase in concentration of micelles along with increase in concentration of Solutol HS 15, because the concentration of Solutol HS 15 used in this study was higher than its critical micelle concentration [8]. This study revealed that Solutol HS 15 is an effective carrier in enhancing solubility and stability of the Pioglitazone HCl. [9]
Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo. With proper timing and dosage, administration of Solutol HS-15 can be an effective therapy against cerebral ischemia. Following ACA, the number of surviving hippocampal neurons was enhanced by Solutol-treated HS15 (68 %) rats as compared to ACA only-treated groups. Infarct volume was decreased by Solutol HS-15 (78 %) as compared to saline (vehicle) in MCAO-treated animals. Solutol HS-15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS-15 is already administered as a solublizing agent to patients.
References:
[1]. Lin H W, Saul I, Gresia V L, et al. Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia[J]. Translational stroke research, 2014, 5(1): 109-117.
[2]. Ku S, Velagaleti R. Solutol HS-15 as a novel excipient[J]. 2010.
[3]. Coon J S, Knudson W, Clodfelter K, et al. Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance[J]. Cancer research, 1991, 51(3): 897-902.
[4]. Shubber S, et al. Mechanism of mucosal permeability enhancement of CriticalSorb? (Solutol? HS15) investigated in vitro in cell cultures. Pharm Res. 2015 Feb;32(2):516-27.
[5].Shamma RN, Basha M. Soluplus: A novel polymeric solubilizer for optimization of Carvedilol solid dispersions: Formulation design and effect of method of preparation. Powder Technol 2013;237:406-14.
[6].Song CK, Yoon IS, Kim DD. Poloxamer-based solid dispersions for oral delivery of docetaxel: Differential effects of F68 and P85 on oral docetaxel bioavailability. Int J Pharm 2016;507(1-2):102-8.
[7].Han HK, Lee BJ, Lee HK. Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: In vitro and in vivo evaluation. Int J Pharm 2011;415(1-2):89-94.
[8].Bravo GonzÁlez RC, Boess F, Durr E, Schaub N, Bittner B. In vitro investigation on the impact of Solutol HS 15 on the uptake of colchicine into rat hepatocytes. Int J Pharm 2004;279(1-2):27-31.
[9]. Swain R P, Subudhi B B, Ramesh P. Effect of Solutol HS 15 in Solid Dispersions of Pioglitazone Hydrochloride: in vitro and in vivo Evaluation[J]. Indian Journal of Pharmaceutical Sciences, 2019, 81(2): 317-325.
Solutol HS-15是一种经过临床批准的辅料，具有神经保护作用。它是一种非离子表面活性剂，化学名称为12-羟基硬脂酸聚氧乙烯酯（polyoxyethylene esters of 12-hydroxystearic acid），在体内毒性低，并能够完全逆转KB 8-5和KB 8-5-11人类表皮样癌细胞的多药耐药性，在敏感的KB 3-1细胞中不会增强药物毒性。此外，Solutol HS-15还可以作为渗透增强剂。
Solutol HS 15可以在其IC50的10%浓度下，分别使KB 8-5-11细胞对秋水仙碱、长春新碱和多柔比星的抗药性降低35倍、28倍和42倍。与维拉帕米类似，Solutol HS 15通过流式细胞术测量，在KB 8-5-11细胞中促进了罗丹明123的50倍积累。此外，Solutol HS 15和维拉帕米将预先装载有罗丹明123的KB 8-5-11细胞从中排出罗丹明123到相似低速率。 Solutol HS 15不影响丙氨酸或葡萄糖进入KB 8-5-11 细胞，表明它对膜活性转运作用并非完全无特异性。
Solutol HS 15是一种第三代表面活性剂载体，用于提高溶解度和生物利用度。使用Solutol HS 15可以将Pioglitazone HCl的溶解度提高约33倍，而Cremophor RH 40只能增加约27倍。此前已经证明了Solutol HS 15具有生理相容性和安全性。随着Solutol HS 15浓度的增加，胶束浓度也同时增加，因为本研究中使用的Solutol HS 15浓度高于其临界胶束浓度。该研究揭示了Solutol HS 15在提高Pioglitazone HCl的溶解度和稳定性方面是一种有效的载体。
Solutol HS 15是一种潜在的治疗药物，因为它在体外可以有效地逆转多药耐药性，并且在体内毒性较低。通过正确的时间和剂量，给予Solutol HS-15可以成为对抗脑缺血的有效治疗方法。 ACA后，与仅接受ACA处理组相比，接受Solutol-treated HS15（68％）处理的大鼠存活海马神经元数量增加了。 MCAO处理动物中，与盐水（载体）相比，Solutol HS-15减少了梗死面积（78％）。 Solutol HS-15在两种缺血范式中都提供强有力的神经保护作用。这可能会证明具有治疗上的益处，因为已将Solutol HS-15作为溶解剂给予患者使用。