Neglected interstitial space in malaria recurrence and treatment

Zhang, Qiang; Ao, Zhuo; Hu, Nan; Zhu, Yuting; Liao, Fulong; Han, Dong

doi:10.1007/s12274-020-2946-y

Cited by 9 publications

(9 citation statements)

References 46 publications

(55 reference statements)

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“…Interstitial uid is the main source of lymph uid, and the delivery of drugs through the interstitial uid may be more suitable than traditional blood delivery for such interstitial diseases. With the aim of increasing the amount of drugs reaching the interstitial uid, we chose ISI as the mode of administration, on the basis of the close connection between PLAM and the interstitium [7,8].…”

Section: Discussionmentioning

confidence: 99%

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Shi

Jiao

et al. 2022

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Shi

Jiao

et al. 2022

Preprint

Self Cite

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show abstract

“…Interstitial fluid is the main source of lymph fluid, and the delivery of drugs through the interstitial fluid may be more suitable than traditional blood delivery for such interstitial diseases. With the aim of increasing the amount of drugs reaching the interstitial fluid, we chose ISI as the mode of administration, on the basis of the close connection between PLAM and the interstitium [ 7 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Shi

Jiao

et al. 2022

Orphanet J Rare Dis

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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.

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“…Bioavailability, concentration, and elimination of drugs are important factors that need to be considered for successful treatment. Nanopharmaceuticals have a promising prospect ( Panzarini et al, 2018 ; Akpa et al, 2020 ; Pestehchian et al, 2020 ; Zhang et al, 2020 ; Guo et al, 2021 ; Wang et al, 2021 ). The application of nano-based delivery systems as carriers of antimalarial drugs has resolved some essential issues, such as increased therapeutic effect of conventional antimalarials with decreased resistance of Plasmodium sp and selective distribution of drugs ( Abazari et al, 2020 ; Rashidzadeh et al, 2021 ) ( Figure 4 ).…”

Section: Resistance To Antimalarialsmentioning

confidence: 99%

Potential of nanoformulations in malaria treatment

Chaves

Moraes²,

Ferrarini³

et al. 2022

Front. Pharmacol.

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Malaria is caused by the protozoan Plasmodium sp and affects millions of people worldwide. Its clinical form ranges from asymptomatic to potentially fatal and severe. Current treatments include single drugs such as chloroquine, lumefantrine, primaquine, or in combination with artemisinin or its derivatives. Resistance to antimalarial drugs has increased; therefore, there is an urgent need to diversify therapeutic approaches. The disease cycle is influenced by biological, social, and anthropological factors. This longevity and complexity contributes to the records of drug resistance, where further studies and proposals for new therapeutic formulations are needed for successful treatment of malaria. Nanotechnology is promising for drug development. Preclinical formulations with antimalarial agents have shown positive results, but only a few have progressed to clinical phase. Therefore, studies focusing on the development and evaluation of antimalarial formulations should be encouraged because of their enormous therapeutic potential.

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Neglected interstitial space in malaria recurrence and treatment

Cited by 9 publications

References 46 publications

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

Potential of nanoformulations in malaria treatment

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