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Microfabricated engineered particle systems for respiratory drug delivery and other pharmaceutical applications.

ABSTRACT: Particle Replication in Non-Wetting Templates (PRINT(®)) is a platform particle drug delivery technology that coopts the precision and nanoscale spatial resolution inherently afforded by lithographic techniques derived from the microelectronics industry to produce precisely engineered particles. We describe the utility of PRINT technology as a strategy for formulation and delivery of small molecule and biologic therapeutics, highlighting previous studies where particle size, shape, and chemistry have been used to enhance systemic particle distribution properties. In addition, we introduce the application of PRINT technology towards respiratory drug delivery, a particular interest due to the pharmaceutical need for increased control over dry powder characteristics to improve drug delivery and therapeutic indices. To this end, we have produced dry powder particles with micro- and nanoscale geometric features and composed of small molecule and protein therapeutics. Aerosols generated from these particles show attractive properties for efficient pulmonary delivery and differential respiratory deposition characteristics based on particle geometry. This work highlights the advantages of adopting proven microfabrication techniques in achieving unprecedented control over particle geometric design for drug delivery.

SUBMITTER: Garcia A

PROVIDER: S-EPMC3307013 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Microfabricated engineered particle systems for respiratory drug delivery and other pharmaceutical applications.

Garcia Andres A Mack Peter P Williams Stuart S Fromen Catherine C Shen Tammy T Tully Janet J Pillai Jonathan J Kuehl Philip P Napier Mary M Desimone Joseph M JM Maynor Benjamin W BW

Journal of drug delivery 20120209

Particle Replication in Non-Wetting Templates (PRINT(®)) is a platform particle drug delivery technology that coopts the precision and nanoscale spatial resolution inherently afforded by lithographic techniques derived from the microelectronics industry to produce precisely engineered particles. We describe the utility of PRINT technology as a strategy for formulation and delivery of small molecule and biologic therapeutics, highlighting previous studies where particle size, shape, and chemistry ...[more]

PMID: 22518316

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Project description:Many technologies ranging from drug delivery approaches to tissue engineering purposes are beginning to benefit from the unique ability of "smart polymers." As a special case, thermo-sensitive hydrogels have great potential, e.g. in actuators, microfluidics, sensors, or drug delivery systems. Here, the loading of Doxorubicin (DOX) with novel thermo-sensitive polymer N-isopropyl acrylamide (PNIPAM) and its copolymers are investigated in order to increase the Doxorubicin's drug efficacy on the targeted tumor site. Therefore, a rational design accurate based on the use of classical molecular dynamics (MD) and well-tempered metadynamics simulations allows for predicting and understanding the behavior of thermo-responsive polymers in the loading of DOX on Hexakis nano-channel at 298 and 320 K. Furthermore, this work investigates the efficacy of this drug carrier for the release of DOX in response to stimuli like variations in temperature and changes in the physiological pH. The study concludes that the Hexakis-polymer composite is capable of adsorbing the DOX at neutral pH and by increasing the temperature of the simulated systems from 298 to 320 K, the strength of intermolecular attraction decreases. In addition, the obtained results of MD simulation revealed that the dominant interaction between DOX and Hexakis in the DOX/polymer/Hexakis systems is the Lennard-Jones (LJ) term due to the formation of strong π-π interaction between the adsorbate and substrate surface. Obtained results show that a higher aggregation of DMA chains around the Hexakis and the formation of stronger bonds with DOX. The results of the well-tempered metadynamics simulations revealed that the order of insertion of drug and polymer into the system is a determining factor on the fate of the adsorption/desorption process. Overall, our results explain the temperature-dependent behavior of the PNIPAM polymers and the suitability of the polymer-Hexakis carrier for Doxorubicin delivery.

Dataset Information

Microfabricated engineered particle systems for respiratory drug delivery and other pharmaceutical applications.

Publications

Microfabricated engineered particle systems for respiratory drug delivery and other pharmaceutical applications.

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