Pharmaceutics (2020-06-01)

Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro/Ex Vivo Studies

  • Miao Wang,
  • Sung-Kyun You,
  • Hong-Ki Lee,
  • Min-Gu Han,
  • Hyeon-Min Lee,
  • Thi Mai Anh Pham,
  • Young-Guk Na,
  • Cheong-Weon Cho

Journal volume & issue
Vol. 12, no. 544
p. 544


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Docetaxel (DTX) has clinical efficacy in the treatment of breast cancer, but it is difficult to develop a product for oral administration, due to low solubility and permeability. This study focused on preparing a self-microemulsifying drug delivery system (SME) loaded with DTX-phospholipid complex ([email protected]), to improve the dissolution and gastrointestinal (GI) permeability of DTX. A dual technique combining the phospholipid complexation and SME formulation described as improving upon the disadvantages of DTX has been proposed. We hypothesized that the complexation of DTX with phospholipids can improve the lipophilicity of DTX, thereby increasing the affinity of the drug to the cell lipid membrane, and simultaneously improving permeability through the GI barrier. Meanwhile, [email protected] SME ([email protected]) increases the dissolution and surface area of DTX by forming a microemulsion in the intestinal fluid, providing sufficient opportunity for the drug to contact the GI membrane. First, we prepared [email protected] by combining dual technologies, which are advantages for oral absorption. Next, we optimized [email protected] with nanosized droplets (117.1 nm), low precipitation (8.9%), and high solubility (33.0 mg/g), which formed a homogeneous microemulsion in the aqueous phase. Dissolution and cellular uptake studies demonstrated that [email protected] showed 5.6-fold higher dissolution and 2.3-fold higher DTX uptake in Caco-2 cells than raw material. In addition, an ex vivo gut sac study confirmed that [email protected] improved GI permeability of DTX by 2.6-fold compared to raw material. These results suggested that [email protected] can significantly overcome the disadvantages of anticancer agents, such as low solubility and permeability.