Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Ahram Canadian University, 6th of October city, Giza, Egypt.
Biolink Egypt for Chemical Industries, 6th of October city, Giza, Egypt.
AAPS PharmSciTech. 2024 Oct 9;25(7):237. doi: 10.1208/s12249-024-02943-2.
Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 350 nm), zeta potential (ZP < -25 mV) and polydispersity index (PDI < 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (-25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and via shunt diffusion. CA-SLN-4 incorporated into Noveon AA-1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and in vitro release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold (p = 0.035) and 4.16 fold (p = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold (p = 0.0005) and 3.83 fold (p = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery via advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment.
脂肪团（CLT）是一种常见的脂肪营养不良综合征，影响全球青春期后的女性。它在解剖学上的特征是呈橘皮状、有凹痕的皮肤外观，因此是一种不可接受的美容问题。CLT 可以通过外科手术来调节，如抽脂和中胚层疗法。但是，这些选择是侵入性的、昂贵的和有风险的。出于这些原因，局部 CLT 治疗更为首选。咖啡因（CA）是一种天然生物碱，以其显著的抗脂肪团作用而闻名。然而，它的亲水性阻碍了它的皮肤渗透。因此，在本研究中，CA 通过高剪切匀化/超声处理被加载到固体脂质纳米粒（SLNs）中。CA-SLNs 是使用 Compritol® 888 ATO 和硬脂酸作为固体脂质，Span 60 和 Brij™35 作为脂质分散稳定剂制备的。通过调整制剂变量来获得包封效率（EE>75%）、粒径（PS<350nm）、Zeta 电位（ZP<-25mV）和多分散指数（PDI<0.5）。选择 CA-SLN-4 并显示出最大的 EE（92.03±0.16%）、最小的 PS（232.7±1.90nm）、最佳的 ZP（-25.15±0.65mV）和 PDI 值（0.24±0.02）。与其余 CA-SLNs 相比，CA-SLN-4 在 1 小时时显示出更高的 CA 释放（99.44±0.36%）。TEM 分析显示 CA-SLN-4 为球形、纳米级囊泡。共聚焦激光扫描显微镜（Con-LSM）分析显示 CA-SLN-4 成功地经皮穿透并通过旁路扩散。将 CA-SLN-4 掺入 Noveon AA-1®水凝胶（CA-SLN-Ngel）中显示出可接受的物理/流变学性质和体外释放曲线。组织学研究表明，CA-SLN-Ngel 与 CA 凝胶相比，在第 7 天和第 21 天分别使皮下脂肪组织（SFT）厚度的平均减少了 4.66 倍（p=0.035）和 4.16 倍（p=0.0001）。与未经处理的组相比，CA-SLN-Ngel 也显著降低了 SFT 厚度，在第 7 天和第 21 天分别为 4.83 倍（p=0.0005）和 3.83 倍（p=0.0043）。这项研究通过提倡皮肤附属物的重要性，为 CA 的皮肤输送开辟了新的途径。因此，CA-SLN-Ngel 可能是一种有前途的纳米化妆品凝胶，可有效治疗 CLT。
