Characterization and uptake studies of various liposomal formulations for drug delivery using human induced pluripotent stem cells
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Date
2021-06-22
Authors
Nizami, Syed Bilal
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Abstract
Drug delivery to the brain is one of the biggest challenges in today’s research. The major hurdle in the development of effective treatments for brain diseases is the presence of the blood-brain barrier (BBB) which separates the blood from the cerebral parenchyma, limiting the transport of many drug molecules to the brain. The recent advancements in the field of nanomedicine offers innovative targeting strategies for drug transport across the BBB. In this study, we developed D-penicillamine loaded liposomal formulations functionalized with PEG, ApoE and/or TAT to achieve a targeted drug delivery to the brain. The liposomes were manufactured using thin-film hydration method and characterized for various parameters such as size, PDI and zeta potential. The size of PEGylated liposomes, ApoE liposomes, TAT liposomes, and ApoE TAT liposomes was found to be 137 nm, 144 nm, 145 nm, and 150 nm whereas the zeta potential was -2.4 mV, -1.89 mV, 0.28 mV, and -0.17 mV, respectively. Moreover, we differentiated endothelial cells (hiPS-ECs) using human induced pluripotent stem cells (hiPSCs) and performed cellular uptake studies of the various liposomal formulations. Cellular uptake of TAT liposomes was observed to be 20-fold higher than the PEGylated liposomes whereas the cellular uptake of ApoE TAT liposomes was 8-fold higher and ApoE liposomes showed a 6-fold increase in uptake. Furthermore, we compared liposomal formulations composed of DSPC and EPC with varying concentrations of cholesterol. We characterized these formulations for parameters such as size, PDI, encapsulation efficiency, and membrane fluidity. DSPC liposomes were found to be the better formulation in terms of encapsulation efficiency. It was also demonstrated that change in cholesterol concentration in DSPC liposomes, did not affect the size, PDI and encapsulation efficiency. In contrast, EPC liposomes showed an increase in encapsulation efficiency and a lower membrane fluidity with the increase in cholesterol concentration.
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Keywords
Brain diseases, Blood-brain barrier (BBB), D-penicillamine