Development and physicochemical characterization of acetalated dextran aerosol particle systems for deep lung delivery

Abstract

Biocompatible, biodegradable polymers are commonly used as excipients to improve the drug delivery properties of aerosol formulations, in which acetalated dextran (Ac-Dex) exhibits promising potential as a polymer in various therapeutic applications. Despite this promise, there is no comprehensive study on the use of Ac-Dex as an excipient for dry powder aerosol formulations. In this study, we developed and characterized pulmonary drug delivery aerosol microparticle systems based on spray-dried Ac-Dex with capabilities of (1) delivering therapeutics to the deep lung, (2) targeting the particles to a desired location within the lungs, and (3) releasing the therapeutics in a controlled fashion. Two types of Ac-Dex, with either rapid or slow degradation rates, were synthesized. Nanocomposite microparticle (nCmP) and microparticle (MP) systems were successfully formulated using both kinds of Ac-Dex as excipients and curcumin as a model drug. The resulting MP were collapsed spheres approximately 1 µm in diameter, while the nCmP were similar in size with wrinkled surfaces, and these systems dissociated into 200 nm nanoparticles upon reconstitution in water. The drug release rates of the Ac-Dex particles were tuned by modifying the particle size and ratio of fast to slow degrading Ac-Dex. The pH of the environment was also a significant factor that influenced the drug release rate. All nCmP and MP systems exhibited desirable aerodynamic diameters that are suitable for deep lung delivery (e.g. below 5 µm). Overall, the engineered Ac-Dex aerosol particle systems have the potential to provide targeted and effective delivery of therapeutics into the deep lung.

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

“…67,68 Spray drying has been used to produce Ac-DEX aerosol microparticles, particularly for pulmonary delivery applications. 46,47,[69][70][71][72] The microscale dry power facilitated the delivery and deposition on the mucosal layer of the lung via inhalation. 47,72 Furthermore, this technique can be used combined with single emulsion or nanoprecipitation.…”

“…46,47,[69][70][71][72] The microscale dry power facilitated the delivery and deposition on the mucosal layer of the lung via inhalation. 47,72 Furthermore, this technique can be used combined with single emulsion or nanoprecipitation. Specifically, drug-loaded Ac-DEX NPs were prepared by conventional oil-in-water single emulsion or nanoprecipitation first, and then spray-dried with excipients (Fig.…”

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“…Particle size and zeta potential results also indicated that spray-drying and freeze-drying processes did not change the physicochemical properties of NPs after re-dispersion. According to previous studies, 27 there is no notable influence on the MMAD of the particles for NPs. Therefore, after inhalation and deposition into the lungs in the form of aggregated particles, NPs could re-dissolve into their nanometer size in the aqueous surroundings on the lung epithelium, and bypass the air–blood barrier and distribute to the extra-pulmonary organs.…”

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity

“…Acdex is composed of acyclic and cyclic acetal groups, with the acyclic acetals degrading faster than the cyclic acetal groups [17]. As a consequence, the degradation behavior of Acdex can be fine-tuned by varying the degree of substitution of the cyclic vs. acyclic acetal groups on the dextran backbone [18]. Most importantly, under slightly acidic conditions (e.g.…”