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首页> 外文期刊>The Internet Journal of Pharmacology >In-Vivo Investigation of the Irritation potential of Lamivudine and Stavudine liposomal gels in rabbits
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In-Vivo Investigation of the Irritation potential of Lamivudine and Stavudine liposomal gels in rabbits

机译：体内拉米夫定和司他夫定脂质体凝胶刺激性的体内研究

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Effective antiretroviral therapy is required on a long-term basis to maintain viral suppression and reduce disease progression in HIV infections. An attempt has been made to implement the principles of novel drug delivery to antiretrovirals in order to overcome the drawbacks of existing therapy. Liposomal gels of lamivudine and stavudine respectively were developed for the transdermal drug delivery. The irritation potential of drug loaded and blank formulations was investigated on shaved rabbit skin, in vivo, and compared to that of 5% sodium lauryl sulphate (SLS) solution (a known irritant) as the positive control and untreated portion of the skin as a negative control. Skin irritation was assessed by visual observations and histological evaluations. We found that the drug loaded and blank liposomal gels caused no significant epidermal irritation and erythema. Thus we conclude that these liposomal gels may be used safely as transdermal drug delivery vehicles for the selected antiretrovirals. Source of Support Department of Science and Technology, New Delhi, India for financial support for the project Introduction Human Immunodeficiency Virus (HIV) is a retrovirus, which causes irreversible destruction of the immune system, leading to the occurrence of AIDS. Effective antiretroviral therapy is required on a long-term basis to maintain viral suppression and reduce disease progression. Currently available anti-HIV drugs bear some significant drawbacks such as relatively short half-life, low bioavailability, poor permeability and undesirable side effects. Efforts have been made to design drug delivery systems for anti-HIV agents to obtain an effective controlled delivery of the drug. An attempt has been made to deliver the antiretrovirals via transdermal route by implementing the principles of novel drug delivery. Transdermal delivery offers a number of advantages such as the avoidance of the first pass effect that usually follows oral delivery [1]. A noninvasive zero – order delivery via transdermal route is desirable for controlled delivery of antiretrovirals. Also vesiculation of the chosen antiretrovirals viz., lamivudine and stavudine will alleviate the toxicity of these molecules. Gel formulations containing liposomal dispersions are being developed for transdermal delivery of drugs [2]. A range of drugs can be solubilised in the gels [34], with the possibility of delivering them into and through the skin. The skin is comprised of different layers, each with distinct properties and functions. The main role of the outer layer, the epidermis, is to act as a barrier, preventing the ingress of harmful chemicals and microbes into the body, while restricting the loss of water and other ions from the body to the environment. Cells in the uppermost layer, the stratum corneum (SC), are cornified and embedded in a lipid matrix [56]. It is this impervious layer that forms the barrier to drug penetration into the skin. It is this layer, therefore, that will be the first point of contact with any topically applied product. Most of the substances interact with skin constituents and might cause reversible or irreversible damage to the skin cells, which must be investigated. Skin irritation is defined as a non-immunological local inflammatory reaction which is usually reversible, and is characterized by erythema and edema, following a single or repeated application of a chemical to the same cutaneous site [78]. All substances can cause irritation to all individuals, and the factors that determine whether a substance will produce irritation in a certain individual include the age, sex, anatomical site, and other factors particular to the individual, as well as the concentration, dose, vehicle, and chemical properties of the irritant, the manner and area of application, and duration of contact. The local inflammatory reaction following perturbation of the epidermal barrier (either by exposure to a physical or chemical irritant) can appear wi
机译：长期需要有效的抗逆转录病毒疗法，以维持病毒抑制作用并减少HIV感染中的疾病进展。为了克服现有疗法的缺点，已经尝试实现将新药递送至抗逆转录病毒药物的原理。拉米夫定和司他夫定的脂质体凝胶分别用于透皮给药。体内研究了剃毛兔皮肤上载有药物和空白制剂的刺激潜力，并将其与作为阳性对照的5％月桂基硫酸钠（SLS）溶液（一种已知刺激物）的刺激潜力和未经处理的皮肤部分进行比较。阴性对照。通过视觉观察和组织学评估来评估皮肤刺激性。我们发现载药和空白脂质体凝胶不会引起明显的表皮刺激和红斑。因此，我们得出结论，这些脂质体凝胶可以安全地用作所选抗逆转录病毒药物的透皮给药载体。印度新德里科学技术部支持项目的资金来源简介人类免疫缺陷病毒（HIV）是一种逆转录病毒，会导致免疫系统不可逆转的破坏，并导致AIDS的发生。长期需要有效的抗逆转录病毒疗法以维持病毒抑制并减少疾病进展。当前可用的抗HIV药物具有一些明显的缺点，例如半衰期相对较短，生物利用度低，通透性差和不良副作用。已经努力设计用于抗HIV试剂的药物递送系统以获得有效的药物受控递送。已经尝试通过实施新型药物递送的原理通过透皮途径递送抗逆转录病毒药物。透皮递送具有许多优点，例如避免了通常在口服递送后出现的首过效应[1]。经由透皮途径的无创零阶递送对于控制抗逆转录病毒剂的递送是理想的。所选抗逆转录病毒药物即拉米夫定和司他夫定的囊泡化也将减轻这些分子的毒性。含有脂质体分散体的凝胶制剂正在开发中，用于药物的透皮给药[2]。可以将多种药物溶解在凝胶中[34]，并有可能将其输送到皮肤中并通过皮肤。皮肤由不同的层组成，每个层具有不同的特性和功能。表皮的外层的主要作用是充当屏障，防止有害化学物质和微生物进入人体，同时限制水分和其他离子从人体向环境的流失。最上层的细胞角质层（SC）被角质化并包埋在脂质基质中[56]。正是这种不可渗透的层形成了药物渗透到皮肤的屏障。因此，正是这一层将成为与任何外用产品接触的第一点。大多数物质与皮肤成分相互作用，可能对皮肤细胞造成可逆或不可逆的损害，必须对此进行研究。皮肤刺激被定义为一种非免疫性局部炎症反应，通常是可逆的，其特征是在同一皮肤部位单次或重复使用化学药品后出现红斑和水肿[78]。所有物质都可能对所有人产生刺激，而确定某种物质是否会在特定个体中产生刺激的因素包括年龄，性别，解剖部位和该个体特有的其他因素，以及浓度，剂量，媒介物，刺激物的化学性质，施用方式和区域以及接触时间。发生表皮屏障干扰后的局部炎症反应（通过暴露于物理或化学刺激物）可能会出现

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