Oral Administration and Selective Uptake of Polymeric Nanoparticles in Larvae as an Model.

In this article, larvae are applied as an model to investigate the transport and uptake of polymeric nanoparticles in the larval digestive tract after oral administration. After feeding the larvae with food containing bare and chitosan-coated Poly(d,l-lactic--glycolic acid) (PLGA) nanoparticles encapsulated with BODIPY, time-lapse imaging of live larvae is used to monitor the movement of fluorescent nanoparticles in the anterior, middle, and posterior midgut of the digestive tract. Also, the dissection of the digestive tract enables the analysis of cellular uptake in the midgut. Bare PLGA nanoparticles travel through the whole midgut smoothly while chitosan-coated PLGA nanoparticles have a long retention time in the posterior midgut. We identify that this retention occurs in the posterior segment of the posterior midgut, and it is termed as the retention segment. During transport in the midgut, chitosan-coated nanoparticles pass through the near-neutral anterior midgut and become highly positively charged when entering into the highly acidic middle midgut. After traveling through the near-neutral anterior segment of the posterior midgut, chitosan-coated nanoparticles have a long retention time of ∼10 h in the retention segment, indicating that the chitosan coating greatly enhances mucoadhesive ability and promotes cellular uptake in this part of the midgut. The dynamic behavior of orally administered nanoparticles in larvae is in agreement with studies in other animal models. A larva has the potential to evolve into a low-cost drug screening model through real time imaging, which will accelerate the development of improved nanoparticle formulations for oral drug delivery.