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. 2022 Sep 9;17(1):349.
doi: 10.1186/s13023-022-02511-6.

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Yahong Shi  1   2 , Chuqiao Jiao  3 , Xi Lu  1   2 , Yifeng Nie  2 , Xiang Li  4 , Dong Han  5
Affiliations

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Yahong Shi et al. Orphanet J Rare Dis. .

Abstract

Background: Pulmonary lymphangiomyomatosis (PLAM) is a rare interstitial lung disease characterized by diffuse cystic changes caused by the destructive proliferation of smooth muscle-like cells or LAM cells. PLAM is more common in young women than other people, and a consensus is lacking regarding PLAM treatment. The clinical treatment of PLAM is currently dominated by rapamycin. By inhibiting the mTOR signaling pathway, rapamycin can inhibit and delay PLAM's occurrence and development. However, the application of rapamycin also has shortcomings, including the drug's low oral bioavailability and a high binding rate to hemoglobin, thus significantly decreasing the amount of drug distributed to the lungs.

Methods and results: Here, we developed a new mode of rapamycin administration in which the drug was injected into the intrathecal space after being nanosized; the directional flow characteristics of the liquid in the intrathecal space were exploited to increase the drug content in the interstitial fluid to the greatest extent possible. We studied the rapamycin content in the interstitial fluid and blood after intervaginal space injection (ISI). Compared with oral administration, ISI significantly increased the drug concentration in the lung interstitial fluid.

Conclusions: These results provided new ideas for treating PLAM and optimizing the dosing regimens of drugs with similar characteristics to rapamycin.

Keywords: Intervaginal space injection (ISI); LC–MS; Pulmonary lymphangiomyomatosis (PLAM); Rapamycin.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Ion mass spectras of rapamycin and parameters of rapamycin liposomes. A Chemical structure of rapamycin. B Precursor ion mass spectra (m/z 936) of rapamycin. C Product ion mass spectras (m/z 409 and m/z 345) of rapamycin. D Particle size distribution of rapamycin liposomes by intensity. E Particle size distribution of rapamycin liposomes by number. F Zeta potential phase plot of rapamycin liposomes. G Schematic diagram and transmission electron microscopy images of the rapamycin liposomes. Scale bars, 500 nm and 100 nm
Fig. 2
Fig. 2
Pharmacokinetic experimental design. A Grouping arrangement and sampling time points of this experiment. B Schematic diagram of the intervaginal space injection (ISI) injection site. C Sample processing flow chart
Fig. 3
Fig. 3
Drug-time curves of whole blood and pulmonary interstitial fluid by P.O. or ISI. A Drug-time curve of pulmonary interstitial fluid by ISI. B Drug-time curve of whole blood by ISI. C Drug-time curve of pulmonary interstitial fluid by P.O. D Drug-time curve of whole blood by P.O. E Time profile of drug content in pulmonary interstitial fluid after ISI or P.O. administration. F Time profile of drug content in whole blood after ISI or P.O. administration
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