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Use of stimulatory responsive soft nanoparticles for intracellular drug delivery

Nano Research 2023年第5期16卷 6974-6990页

作者： Krystal A Hughes Bishal Misra Maryam Maghareh Sharan Bobbala Department of Pharmaceutical Sciences West Virginia University School of PharmacyMorgantownWV 26505USA Department of Clinical Pharmacy West Virginia University School of PharmacyMorgantownWV 26505USA

Drug delivery has made tremendous advances in the last decade.Targeted therapies are increasingly common,with intracellular delivery highly impactful and sought after.Intracellular drug delivery systems have limitations due to imprecise and non-targeted release profiles.One way this can be addressed is through using stimuli-responsive soft nanoparticles,which contain materials with an organic backbone such as lipids and polymers.The choice of biomaterial is essential for soft nanoparticles to be responsive to internal or external stimuli.The nanoparticle must retain its integrity and payload in non-targeted physiological conditions while responding to particular intracellular environments where payload release is desired.Multiple internal and external factors could stimulate the intracellular release of drugs from nanoparticles.Internal stimuli include pH,oxidation,enzymes,while external stimuli include ultrasound,light,electricity,magnetic fields.Stimulatory responsive soft nanoparticulate systems specifically utilized to modulate intracellular delivery of drugs are explored in this review.

关键词： nanoparticles biomaterials stimuli-responsive targeted delivery intracellular drug delivery

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Polymersomes scalably fabricated via flash nano- precipitation are non-toxic in non-human primates and associate with leukocytes in the spleen and kidney following intravenous administration

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Nano Research 2018年第10期11卷 5689-5703页

作者： Sean D. Allen Yu-Gang Liu Sharan Bobbala Lei Cai Peter I. Hecker Ryan Temel Evan A. Scott Interdisciplinary Biological Sciences Northwestern University IL 60208 USA Department of Biomedical Engineering Northwestern University IL 60208 USA Saha Cardiovascular Research Center University of Kentucky KY40506 USA Department of Pharmacology and Nutritional Sciences University of Kentucky KY40506 USA

Vesicular nanocarrier formulations confer the ability to deliver hydrophobic and hydrophilic cargos simultaneously to cells of interest in vivo. While liposomal formulations reached the clinic long ago, younger technologies such as polymeric vesicles （polymersomes） have yet to make the transition to clinical approval and use, in part due to difficulties in ensuring their safe and scalable production. In this work, we demonstrate the scalable production of poly（ethylene glycol）-block-poly（propylene sulfide）（PEG-bl-PPS） polymersomes via flash nanoprecipitation, and further show the safe administration of these nanocarriers to mice and non-human primates. In mice, PEG-bl-PPS polymersomes were found to be well tolerated at up to 200 mg/（kg.week）. Following the administration of a more relevant 20 mg/（kg.week） dosage in non-human primates, polymersomes were found to associate with numerous phagocytic immune cell populations, including a remarkable 68% of plasmacytoid dendritic cells and 〉 95% of macrophages in the spleen, while showing no toxicity or abnormalities in the liver, kidney, spleen, or blood. Despite the presence of a dense PEG corona, neither anti-PEG antibodies nor complement activation were detected. This work provides evidence of the translatability of PEG-bI-PPS polymersomes into the clinic for therapeutic applications in humans.

关键词： polymersome non-human primate nanoprecipitation toxicity biodistribution

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