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Liposome-based systems for the intravitreal delivery of oligonucleotides

机译:基于脂质体的寡核苷酸纤维素递送的系统

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Antisense oligonucleotides were recently proposed for the treatment of cytomegalovirus (CMV) infection. Treatment of CMV infection is usually given by the systemic route. However, systemic administration of antivial drugs in ophthalmic therapy has serious drawbacks, such as renal and hematological toxicity. For these reasons, intravitreal injection may be considered as an interesting alternative to systemic delivery. This administration route is however very delicate to handle since the needle must penetrate the vitreous humor without causing retinal disruption or detachement. Moreover, the patient must remain under local anesthesia during injection. Therefore, an ideal intravitreal drug delivery system should prolong the duration of action of antiviral drugs and also improve drug activity and avoid toxicity. In thi contrext, we have designed a new drug delivery system, which consist in sterically stabilized liposomes dispersed within a thermosensitive poloxamer 407 gel. Poloxamer 407 at high concentration and above 18 deg C undergo a transition from a solution to a gel In the present study, we have compared the ocular tissue distribution of a model oligonucleotide (pdT16) injected intravitreally as a simple solution, encapsulated in liposomes or in liposomes dispersed within a thermosensitive gel.
机译:最近提出反义寡核苷酸用于治疗细胞瘤病毒(CMV)感染。系统途径通常给予CMV感染的处理。然而,在眼科治疗中的抗衰期药物施用具有严重缺点,例如肾和血液毒性。由于这些原因,玻璃体内注射可能被认为是对系统性交付的有趣替代品。然而,该管理途径非常微妙地处理,因为针必须穿透玻璃体幽默而不会导致视网膜破坏或脱落。此外,患者必须在注射期间留在局部麻醉下。因此,理想的玻璃体药物输送系统应延长抗病毒药物的作用持续时间,并改善药物活性并避免毒性。在对照文本中,我们设计了一种新的药物递送系统,其在分散在热敏泊洛昔尔407凝胶内的空质稳定脂质体中。在高浓度和高于18℃以上的泊洛沙姆407经历从溶液中的过渡到本研究中,将模型寡核苷酸(PDT16)的眼部组织分布与含有简单的溶液中的一种简单的溶液进行了比较,以脂质体或在脂质体中包封分散在热敏凝胶内的脂质体。

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