Formulation Development of Doxycycline-Loaded Lipid Nanocarriers using Microfluidics by QbD Approach

Chia Ying Lee, Chi Ting Su, Tsuimin Tsai, Chien Ming Hsieh, Kuan Yu Hung, Jeng Wen Huang, Chin Tin Chen

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Liposomes have been used to improve therapeutic efficacy of drugs by increasing their bioavailability and altering biodistribution. The loading capacity of small molecules in liposomes remains a critical issue. Besides, the manufacturing process of liposomes requires multi-step procedures which hinders the clinical development. In this study, we developed a promising lipid-based nanocarriers (LN) delivery system for hydrophilic charged compounds using doxycycline (Doxy) as a model drug. This Doxy-loaded lipid nanocarrier (LN-Doxy) was fabricated by microfluidic technology. Design of experiments (DoE) was constructed to outline the interactions among the critical attributes of formulation, the parameters of microfluidic systems and excipient compositions. Response surface methodology (RSM) was furthered used for the optimization of LN-Doxy formulation. The LN-Doxy developed in this study showed high drug to lipid ratio and uniform distribution of particle size. Compared to Doxy solution, this LN-Doxy has reduced in vitro cellular toxicity and significant therapeutic efficacy which was verified in a peritonitis animal model. These results show the feasibility of using microfluidic technology combined with QbD approach to develop the LN formulation with high loading efficiency for ionizable hydrophilic drugs.

Original languageEnglish
Pages (from-to)740-750
Number of pages11
JournalJournal of Pharmaceutical Sciences
Issue number3
Publication statusPublished - Mar 2023


  • Design of experiment
  • Doxycycline
  • Lipid-based nanocarrier
  • Microfluidics

ASJC Scopus subject areas

  • Pharmaceutical Science


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