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Bringing the pulsatile release system to light - Nature Computational Science
Bringing the pulsatile release system to light
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Published: 15 August 2022 .
DRUG DELIVERY
Bringing the pulsatile release system to light .
Fernando Chirigati 1 ? .
Nature Computational Science ( 2022 ) Cite this article
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Biomedical engineering .
Drug delivery .

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Sci. Adv . 8 , eabn5315 (2022)
Oral drug delivery is a common route for drug administration, in which the typical pattern for drug release consists in reaching and maintaining a constant drug level for a specified period of time. Some conditions, however, require pulsatile drug delivery systems (PDDS), in which a drug is delivered only after a predetermined off-released period, or a lag time. Examples of drugs that need PDDS include those that develop biological tolerance, those that are targeted to a specific site in the intestinal tract, and those that need to adapt to circadian rhythms of body functions or diseases. Biodegradable core-shell microparticles are a promising class of biomaterials for PDDS, since their hollow core-shell structure displays pulsatile release kinetics. Nevertheless, the mechanism of pulsatile release from microparticles upon degradation remains poorly understood.
In a recent work, Robert Langer, Ana Jaklenec and colleagues performed a study using experimental and computational tools in a complementary way to obtain more insights into the aforementioned mechanism. On the computational front, the authors developed a numerical multi-physics model for simulating particle deformation, which was particularly useful to study the effect of dimensionless parameters not captured in the experiments, such as the permeability ratio of the microparticle cap to its base. As a result of their study, pore formation and deformation in the cap were found to be the two governing parameters that control the release kinetics: the pore formation in poly(lactic-co-glycolic acid) microparticles could be used as a gate to enable the pulsatile release of the drug. The authors also found that deformation patterns on the cap were noticed primarily 2 days after incubation, with the creation of a pore-forming zone on the edge of the cap. Interestingly, within the studied range of cap thickness, the release profile was found to be independent of particle geometry, and particle composition (instead of size or morphology) was found to dominate the release time point. The computational model matched the trend of experiments and pointed to the presence of three different modes of cap deformation. On the whole, the unique combination of experiments and simulations improves our understanding of pulsatile release, which can aid in the design and fabrication of next-generation biomaterials and drug delivery systems.
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Fernando Chirigati
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Chirigati, F. Bringing the pulsatile release system to light. Nat Comput Sci (2022). https://doi.org/10.1038/s43588-022-00307-z
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Published : 15 August 2022
DOI : https://doi.org/10.1038/s43588-022-00307-z
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