Bioimaging of Intact Polycaprolactone Nanoparticles Using Aggregation‐Caused Quenching Probes: Size‐Dependent Translocation via Oral Delivery

Abstract

The limited information on biological fate impedes the development of more efficient polymeric nanoparticles for oral delivery of bio‐macromolecules. In this study, the in vivo fate as well as the trans‐epithelia transport of polycaprolactone (PCL) nanoparticles is explored by labeling with aggregation‐caused quenching probes, which is capable of identifying intact nanoparticles. Live imaging and confocal laser scan microscopy confirm size‐dependent absorption of PCL nanoparticles. In general, reducing particle size favors a faster and more oral absorption. Nanoparticles larger than 200 nm, such as 600 and 2000 nm, cannot be efficiently transported across the intestinal membrane. The absorbed nanoparticles (50 and 200 nm) mainly accumulate in the liver. Lymph may be the main absorption route for PCL nanoparticles, transporting 2.39 ± 1.81% and 0.98 ± 0.58% of administered 50 and 200 nm nanoparticles, respectively. Cellular uptake and transportation of PCL nanoparticles are also size dependent. Both enterocytes and M cells mediated transcytosis are involved in the transport of 50 nm PCL nanoparticles, while the M cell pathway is dominative for other nanoparticles. In conclusion, the study provides a valuable tool for bioimaging of intact polymeric nanoparticles as well as solid evidence supporting size‐dependent translocation of the nanoparticles via oral delivery.

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives

“…Therefore, the fluorescence indicates the intact vehicles. The in vivo fates of various nanoparticles (e.g., polymeric nanoparticles, micelles, nanoemulsions, and nanocrystals) via different routes (e.g., oral, intravenous, transdermal, nasal, and ocular routes) have been explored by using the ACQ probes [146][147][148][149].…”

An update on oral drug delivery via intestinal lymphatic transport

“…The size effect was investigated by tracking the translocation of polycaprolactone (PCL) nanoparticles labeled by near-infrared fluorescent probes with aggregation-caused quenching (ACQ) properties 48 , 158 . After oral administration, more particles of the 600 and 2000 nm groups were transported via the lymphatics than the smaller size groups (50 and 200 nm), evidenced by quantification of particles in lymph collected through mesenteric lymphatic duct cannulation 48 , 158 . The particle size effect of nanocrystals was investigated by employing similar ACQ-based bioimaging strategy.…”

“…If nanoparticles are able to be absorbed intact, there are chances for them to be transported into the systemic circulation, and they may preferably choose the lymphatic pathway because of the fenestrated walls of the lymphatics 196 . This is especially the case for small-sized PCL nanoparticles (50 nm) which are taken up more profoundly by in vitro Caco-2 cell models and transported more efficiently via the lymphatics 158 . Except for this leakage-aided process, receptor-mediated transport via lymphatics was also proposed 197 .…”

Peroral targeting of drug micro or nanocarriers to sites beyond the gastrointestinal tract

“…A majority of particulates and macromolecules that permeate across the enteric epithelia tend to be flushed via the lymphatics and then join the systemic circulation at the subclavian vein. The lymphatic transport efficiency of nonspecific nanocarriers is generally very low−less than 5% of the original dose, as evidenced by quantification of nanoemulsions, 7 solid lipid nanoparticles (SLNs), 8,9 polycaprolactone nanoparticles 10 and methoxy polyethylene glycol‐polylactic acid (mPEG‐PLA) polymeric micelles 11 in lymph collected by mesentery lymphatic cannulation. In rare cases, higher lymphatic transport could be attained, for example, in the case of SLNs fortified with orlistat, a lipase inhibitor, to slow down lipolysis 8 .…”