PLGA-PEG derivatives from PolySciTech used in development of muscle-targeting nanoparticles for muscular dystrophy treatment

Muscular dystrophy (Duchenne) is the most common inherited muscular disease which leads to degeneration of muscle tissue until the patient can no longer breathe at which point it becomes fatal. This disease is driven by a lack of functional dystrophin in muscle fibers which reduces their resistance to mechanical stress during contraction. Recently, researchers at Purdue University used mPEG-PLGA (AK037), PLGA-PEG-NHS (AI111), PLGA-PEG-NH2 (AI188) from PolySciTech (www.polyscitech.com) to create muscle-targeting nanoparticles to deliver VO-OHpic which prevents PTEN pathway of muscular degradation. This research holds promise to provide a treatment for this debilitating disease. Read more: Huang, Di, Feng Yue, Jiamin Qiu, Meng Deng, and Shihuan Kuang. "Polymeric nanoparticles functionalized with muscle-homing peptides for targeted delivery of phosphatase and tensin homolog inhibitor to skeletal muscle." Acta Biomaterialia (2020). https://www.sciencedirect.com/science/article/pii/S1742706120305985

“Phosphatase and tensin homolog (PTEN) antagonizes muscle growth and repair, and inhibition of PTEN has been shown to improve the pathophysiology and dystrophic muscle function in a mouse model of Duchenne muscular dystrophy (DMD). However, conventional pharmacological delivery of PTEN inhibitors carries a high risk of off-target side effects in other non-muscle organs due to broad targeting spectrums. Here we report a muscle-targeted nanoparticulate platform for cell-specific delivery of a PTEN inhibitor. Poly(lactide-co-glycolide)-b-poly(ethylene glycol) nanoparticles (NPs) are functionalized with a muscle-homing peptide M12 to promote the selective uptake by muscle cells/tissue in vitro and in vivo. Moreover, the NPs are formulated to slowly release the PTEN inhibitor, preventing cytotoxicity associated with direct exposure to the drug and facilitating sustained inhibition of PTEN. This advanced delivery approach taking advantages of polymeric nanomaterials and muscle-homing peptides opens a new avenue for the development of long-term therapeutic strategies in DMD treatment. Pharmacological inhibition of phosphatase and tensin homolog (PTEN) has been demonstrated to improve muscle function in a mouse model of Duchenne muscular dystrophy (DMD), but translation of this approach into clinical settings remains challenging due to potential risks of off-target side effects. Herein, we developed a nanoparticulate platform, consisting of poly(lactide-co-glycolide)-b-poly(ethylene glycol) and a muscle-homing peptide M12, for cell-specific delivery of a PTEN inhibitor. M12 facilitates the cellular internalization of nanoparticles in myoblasts and their selective localization in skeletal muscle. Moreover, the slowly released drug from nanoparticles reduces its cytotoxicity and achieves sustained PTEN inhibition. This advanced delivery approach taking advantages of nanomaterials and targeting peptides opens a new avenue for the development of long-term therapeutic strategies in DMD treatment.”