The effects of charge on inhaled rapamycin solid lipid nanoparticles for lymphatic targeting

Emelie Landh, Lyn M. Moir, Daniela Traini, Paul M. Young, Hui Xin Ong

Research output: Chapter in Book/Report/Conference proceedingConference proceeding contributionpeer-review

Abstract

Lymphangioleiomyomatosis (LAM) is a progressive lung disease caused by mutational inactivation of tuberous sclerosis complexes 1 and 2 (TSC1&2). This results in uncontrolled growth and proliferation of smooth muscle cells in the lungs resulting in cysts and breathing problems. Muscle cells can spread via the lymphatic system to the kidneys, liver and lymph nodes. The use of oral rapamycin to treat LAM is limited by its low bioavailability (~15%) and side effects such as hypertension and lymphedema. Inhaled solid lipid nanoparticles of rapamycin (Rapa-SLN) 200 nm in size have shown promising in vitro results by accessing the lymphatic endothelium via the pulmonary route faster than larger Rapa-SLNs and un-encapsulated rapamycin. The current study extends this work to investigate the effect of surface charge on the ability of Rapa-SLNs to access the lymphatic system via the lungs by adding two different charge-modifying additives. Polyethylene glycol 2000 (PEG2000) is a molecule approved by the FDA for use in medical applications and is commonly used in the preparations of liposomes and solid lipid nanoparticles. In this study we hoped to use its amphilic nature to neutralize the negative charge observed on the original Rapa-SLN formulation. Similarly, Hexacyltrimethylammonium bromide (CTAB), cationic in nature, has been shown by previous research to act as a reducing agent in nanoparticle generation, and was therefore chosen as the positive charge inducing additive for the present study.
Original languageEnglish
Title of host publicationRespiratory Drug Delivery 2020
EditorsR. N. Dalby, P. R. Byron, M. Hindle, J. Peart, D. Traini, P. M. Young, S. J. Farr, J. D. Suman, A. Watts
Place of PublicationRichmond, VA
PublisherRDD Online
Pages753-758
Number of pages6
Volume3
ISBN (Electronic)9781942911487
Publication statusPublished - 2020
Externally publishedYes
EventRespiratory Drug Delivery 2020 - Palm Desert, United States
Duration: 26 Apr 202030 Apr 2020

Conference

ConferenceRespiratory Drug Delivery 2020
CountryUnited States
CityPalm Desert
Period26/04/2030/04/20

Keywords

  • lymphangioleiomyomatosis (LAM)
  • rapamycin
  • solid lipid nanoparticles
  • lymphatic system
  • surface charge

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