Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
J Control Release. 2024 Oct;374:76-88. doi: 10.1016/j.jconrel.2024.07.080. Epub 2024 Aug 10.
The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faces challenges due to poor solubility and low bioavailability. This study explores the development of dissolving microneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention, aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soya lecithin, water, and polysorbate 80 micelles. MNs were created from poly(vinyl alcohol) and poly(vinylpyrrolidone) hydrogels by adding polymer powder directly into ethosomes suspensions, reducing manufacturing time and cost. Two methods were used to load ethosomes into high-density moulds: 1) only in the needle area, and 2) in both the needle area and baseplate. Dynamic light scattering confirmed nanostructures in the hydrogels and MNs. Micelle-based ethosomes dissolved MNs in 15 min, compared to 30 min for other MNs. Skin deposition studies showed greater drug deposition (up to 10 μg/patch) and enhanced skin permeation of FENR (up to 40 μg) with Method 2. In-vivo studies in rats demonstrated that oral administration resulted in plasma FENR levels below 10 ng/g in the first three hours, whereas MN administration delayed delivery, reaching a maximum plasma concentration of 52 ng/g at 48 h. Skin deposition of FENR from MNs decreased from 3 μg/g on day 1 to <0.3 μg/g by the last day. This study indicates that MNs are a potential minimally invasive dosage form for delivering FENR, offering a new approach for breast cancer chemoprevention.
视黄酸芬维 A 酯（FENR）是一种有前途的预防乳腺癌复发的化合物，但由于溶解度差和生物利用度低而面临挑战。本研究探索了含有 FENR 负载醇质体的溶解微针（MNs）的开发，用于微创乳腺癌化学预防，旨在增强局部药物分布。醇质体是由乙醇、丙二醇、大豆卵磷脂、水和聚山梨醇 80 胶束制成的。MNs 是通过将聚合物粉末直接添加到醇质体悬浮液中，从聚乙烯醇和聚乙烯吡咯烷酮水凝胶中制成的，从而减少了制造时间和成本。有两种方法将醇质体加载到高密度模具中：1）仅在针区域，2）在针区域和基底层。动态光散射证实了水凝胶和 MNs 中的纳米结构。基于胶束的醇质体在 15 分钟内溶解 MNs，而其他 MNs 需要 30 分钟。皮肤沉积研究表明，与其他 MNs 相比，方法 2 具有更大的药物沉积（高达 10μg/贴）和增强的 FENR 皮肤渗透（高达 40μg）。在大鼠体内研究中，口服给药导致前三个小时血浆中 FENR 水平低于 10ng/g，而 MN 给药延迟了药物的释放，在 48 小时达到最大血浆浓度 52ng/g。MN 给药后皮肤中 FENR 的沉积量从第 1 天的 3μg/g 减少到最后 1 天的<0.3μg/g。这项研究表明，MNs 是一种有潜力的微创给药形式，可用于递送 FENR，为乳腺癌化学预防提供了一种新方法。
