||Samrat Mazumdar, Deepak Chitkara, Anupama Mittal. Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers[J]. Acta Pharmaceutica Sinica B, 2021, 11(4): 903-924
|Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers
|Samrat Mazumdar, Deepak Chitkara, Anupama Mittal
|Department of Pharmacy, Birla Institute of Technology and Science(BITS-PILANI), Pilani, Rajasthan 333031, India
|The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways. Similarly, a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria, endoplasmic reticulum (ER) and Golgi. This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization. Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specific endocytic pathway.
|Funds: This work was financially sponsored by extramural research funding support from Department of Science and Technology, Rajasthan (Project #P.7 (3) Wipro/R&D/2016/6009, India). The authors have no other relevant affiliation or financial support with any organization with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. We also acknowledge Biorender for their technical support in the creation of the figures.
|Corresponding author: Anupama Mittal, firstname.lastname@example.org
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