Nanocomposite microparticles (nCmP) for the delivery of tacrolimus in the treatment of pulmonary arterial hypertension

Abstract

Tacrolimus (TAC) has exhibited promising therapeutic potential in the treatment of pulmonary arterial hypertension (PAH); however, its application is prevented by its poor solubility, instability, poor bioavailability, and negative systemic side effects. To overcome the obstacles of using TAC for the treatment of PAH, we developed nanocomposite microparticles (nCmP) for the pulmonary delivery of tacrolimus in the form of dry powder aerosols. These particles can provide targeted pulmonary delivery, improved solubility of tacrolimus, the potential of penetration through mucus barrier, and controlled drug release. In this system, tacrolimus-loaded polymeric nanoparticles (NP) were prepared via emulsion solvent evaporation and nCmP were prepared by spray drying these NP with mannitol. The NP were approximately 200 nm in diameter with narrow size distribution both before loading into and after redispersion from nCmP. The NP exhibited smooth, spherical morphology and the nCmP were raisin-like spheres. High encapsulation efficacy was achieved both in the encapsulation of tacrolimus in NP and that of NP in nCmP. nCmP exhibited desirable aerosol dispersion properties, allowing them to deposit into the deep lung regions for effective drug delivery. A549 cells were used as in vitro models to demonstrate the non-cytotoxicity of TAC nCmP. Overall, the designed nCmP have the potential to aid in the delivery of tacrolimus for the treatment of PAH.

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

“…Ac-Dex-5min exhibited 61.2% cyclic acetal coverage (CAC) and 71.6% total conversion of -OH groups, while Ac-Dex-3h exhibited 82.5% CAC and 80.0% total conversion of -OH groups, which matched our previous results (Wang et al, 2016; Wang and Meenach, 2016). The Ac-Dex with longer synthesis time (Ac-Dex-3h) exhibited a higher CAC, which was in accordance with previous studies.…”

Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

“…Furthermore, the presented high loading capacities for DX (5.8% in tNG_dPG_tPG and 6.8% in tNG_dPG_pNIPAM) are comparable to other highly efficient nanocarrier systems (Kim & Martin, 2006;Sun et al, 2015). The TAC loading in tNG_dPG_tPG (2.5%) and tNG_dPG_pNIPAM (0.9%) was also comparable to other highly efficient nano-based systems (Wang et al, 2016;Xu et al, 2014;Zhao et al, 2015). As the drugs TAC and DX are used for the treatment in skin, it is of high importance that the drugs are being released in the viable epidermis targeting immune cells within the skin.…”

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

“…5a). 47,70,73 For example, Torrico Guzmán et al formulated paclitaxel loaded Ac-Dex NPs via single emulsion, and then spray-dried along with mannitol. 46 The paclitaxel loaded NPs were ca.…”

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