Objective  To improve the water solubility of natural drugs and the efficiency of their transport into the brain, to prepare nanogel dropping pills modified with lactoferrin for loading poorly soluble drugs and investigate the preparation process, and to provide a reference for drug development in the field of neurodegenerative diseases.

Methods    Using the insoluble drug icariin as the payload, the lactoferrin-modified zinc alginate nanogels were prepared by the reverse-phase microemulsion method. The drug loading and encapsulation rates of icariin in the nanogel were determined by HPLC. Taking the utilizing parameters such as roundness, weight difference and disintegration time as evaluation indicators, the best preparation process of dropping pills was optimized by single factor experiments and Box-Behnken response surface methodology. It was characterized by Fourier transform infrared spectroscopy, the release behavior of nanogel in dropping pills was explored by basket rotating method, and the brain entry efficiency between sublingual and oral administration of drip pills were compared by fluorescence tracing method.

Results  The drug loading rate of the nanogel was (2.67 ± 0.05)%, and the encapsulation rate was (84.74 ± 0.03)% by HPLC. The optimal preparation process for lactoferrin modified nanogel dropping pills was as follows: the ratio of matrix to nano gel was 5:1, the drop distance was 5.5 cm, and the condensation temperature was 8.5 ℃. Using the modified lactoferrin as a marker, its cumulative release rate in vitro reached 92.25%. Fluorescence tracing studies  showed that compared to the oral group, sublingual administration of dripping pills facilitated the faster and more effective passage of drugs through the blood-brain barrier, significantly enhanced the efficiency of drug transport into the brain.

Conclusion  The prepared lactoferrin-modified nanogels can be used as a loading platform for poorly soluble drugs and enhance the drug solubility. When further formulated into dripping pills, it significantly enhances the efficiency of drug transport into the brain after sublingual administration. This also enhances medication compliance among neurodegenerative patients and fulfills the clinical demand for the drug.

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