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| 2024-03-27 09:23:32 | onclick： | New dosage form for overcoming biological multi-barrier drugs |
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Professor Kang Huafeng, Associate Professor Ma Xiaobin and Professor Wu Hao of the Center for Cancer Surgery/Mammary Diseases of Xi'an Jiaotong University's Second Affiliated Hospital have made progress in the development of new forms of biological multi-barrier drugs.
Patients with advanced non-small cell lung cancer are prone to brain metastasis and have a short life cycle with poor prognosis.In first-line clinical treatment, neither immunotherapy (such as PD-L1 monoclonal antibody) nor chemotherapy (such as paclitaxel, PTX) can effectively inhibit tumor progression.There are many reasons for this dilemma. For PD-L1 monoclonal antibody, it is easy to cause irAEs, and its molecular weight is large, and it cannot cross the blood-brain barrier.For paclitaxel, it can not overcome the blood circulation barrier, blood-brain barrier and lack of tumor targeting, so the bioavailability is low.
To overcome the biological multi-barrier delivery of biological macromolecule PD-L1 monoclonal antibodies, the team developed a new form of MB-aPDL1 monoclonal antibody that is super responsive to the tumor microenvironment.After screening the borate bonds with different structures, it was found that the pyridine borate bonds formed by pyridine boric acid (BPA) and maltose acid (MA) had obvious molecular switching between pH 6.8-6.5.Subsequently, the team applied it to the development of a new form of the PD-L1 monoclonal antibody, MB-aPDL1, which showed that the drug could block its biological function before responding to the release of antibodies and restore its original therapeutic function.In addition, the formulation not only prolongs blood circulation while ensuring minimal antibody leakage, but also ensures structural integrity in the physiological environment, accurate release of antibodies in the tumor microenvironment.Ultimately, MB-aPDL1 improved the tumor immune microenvironment, improved the immunotherapy effect of NSCLC brain metastasis, and significantly reduced the adverse effects of immunotherapy itself.
To improve the bioavailability of the small molecule drug paclitaxel, the team collaborated to develop a new form of paclitaxel, BPM-PD@PTX.The drug modifies pyridine boric acid (BPA) and maltose acid (MA) to DSPE-PEG1.5k with amphiphilic phospholipid structure and loads PTX to form a stable cross-linked structure for the treatment of NSCLC brain metastasis.The results show that BPM-PD@PTX can overcome the biological multi-barrier concentration in the brain metastasis, and release paclitaxel accurately, which significantly prolongs the life cycle and shows detoxification.
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