Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via Ugo La Malfa 153, 90146, Palermo, Italy.
Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi, 32, 90123, Palermo, Italy.
AAPS PharmSciTech. 2019 Jan 2;20(1):18. doi: 10.1208/s12249-018-1202-1.
Nowadays, chemoprevention by administering natural supplements is considered an attractive strategy to reverse, suppress, or prevent the evolution of premalignant oral lesions. In particular, Barbaloin exhibits anti-proliferative, anti-inflammatory, and anti-cancer properties, and it results useful in multi-therapy with classic chemotherapeutics. Therefore, in this work, mucoadhesive buccal films, as locoregional drug delivery system able to provide a targeted and efficient therapeutic delivery of Barbaloin, are proposed. Thus, Aloin extract-loaded Eudragit® RL100 or Eudragit® RS100-based buccal films were designed in order to obtain an easily self-administrable formulation capable of promoting Barbaloin penetration into buccal mucosa and assuring high patient compliance. Large amounts of extract (44%) were loaded into the polymer matrix and six formulations were prepared varying polymers and plasticizers ratios. For all formulations, physical form (thermogravimetric analysis-differential scanning calorimetry, TGA-DSC), swelling degree, mucoadhesiveness, drug release, and ability to promote drug penetration in mucosa have been investigated. After a sequential selection process, Eudragit RS 100-based film, with low PVP and high plasticizers amounts, emerged as the most promising. It results appropriately flexible, uniform in terms of weight, thickness and drug content, as well as characterized by suitable surface pH, good mucoadhesiveness, and low swelling degree. It displays a Higuchian drug release behavior up to 89% of Barbaloin released, thus demonstrating that diffusion through the matrix is the main release mechanism. Remarkable penetration enhancer properties of film were demonstrated by evidence of Barbaloin accumulation into buccal mucosa up to 10-fold higher than those obtained following administration of Aloin solution.
如今，通过服用天然补充剂进行化学预防被认为是一种有吸引力的策略，可以逆转、抑制或预防癌前口腔病变的发展。特别是，芦荟大黄素具有抗增殖、抗炎和抗癌特性，与经典化疗药物联合使用非常有用。因此，在这项工作中，提出了粘膜粘附颊膜作为局部药物递送系统，能够提供靶向和有效的芦荟大黄素治疗递送。因此，设计了含有芦荟素提取物的 Eudragit® RL100 或 Eudragit® RS100 颊膜，以获得易于自我管理的制剂，能够促进芦荟大黄素渗透到口腔颊粘膜，并确保高患者依从性。大量提取物（44%）被载入聚合物基质中，并制备了六种不同聚合物和增塑剂比例的制剂。对于所有制剂，都研究了物理形态（热重分析-差示扫描量热法，TGA-DSC）、溶胀度、粘膜粘附性、药物释放以及促进药物渗透到粘膜的能力。经过一系列的选择过程，Eudragit RS 100 为基础的膜，具有低 PVP 和高增塑剂含量，成为最有前途的。它结果是适当的灵活性，在重量、厚度和药物含量方面均匀，并且具有合适的表面 pH 值、良好的粘膜粘附性和低溶胀度。它显示出 Higuchian 药物释放行为，芦荟大黄素释放高达 89%，这表明通过基质的扩散是主要的释放机制。膜的显著渗透增强特性通过证据证明，芦荟大黄素在口腔颊粘膜中的积累比使用芦荟素溶液时高 10 倍。
