Fabrication of polymeric nanoparticles of poly(ethylene‐co‐vinyl acetate) coated with chitosan for pulmonary delivery of carvedilol

Abstract

Carvedilol is a drug with low oral bioavailability due to its high first-pass metabolism. The purpose of the present study was to prepare a mucoadhesive dry powder inhaler of this drug loaded in poly(ethylene-co-vinyl acetate)(PEVA) nanoparticles for pulmonary delivery. PEVA nanoparticles were prepared by an O/W solvent evaporation method and coated with different concentrations of chitosan as a mucoadhesive polymer. Encapsulation efficiency, particle size, zeta potential, release efficiency, and mucoadhesive properties of the different formulations were evaluated on mucin substrate. The optimized formulation of nanoparticles was spray dried using lactose and mannitol as carrier powders. The flowability of the obtained powders was checked by Carr's Index and Hausner ratio and the in vitro deposition of the aerosolized drug was investigated using a Next Generation Impactor. Increasing in the particle size and zeta potential of nanoparticles confirmed the settling of the chitosan coating layer on the surface of nanoparticles. The in vitro drug release from coated nanoparticles decreased with increasing of chitosan concentration. Mucoadhesive property of chitosan-coated PEVA nanoparticles was higher than noncoated ones. Spray-dried powders had different aerosilization behavior. Mannitol-based formulation was found to have low density, better flow ability, smaller aerodynamic diameter (d aer ) and higher fine powder fraction. The results of the present study allow concluding that mannitol spray dried, mucoadhesive nanoparticles of PEVA are suitable inhaler powder for pulmonary delivery of carvedilol.

Recent Developments in Application of Polymeric Nanoparticles as Drug Carriers

“…The numerous advantages offered by polymeric nanoparticles as drug delivery systems (DDSs) also include the extension of drug circulation time in the body [10], increased stability of acid-labile drugs [11], uniform drug distribution in the targeted site e.g. alveoli [12], high drug encapsulation efficiency [13] and stimuli-responsiveness e.g. to oxidative stress [14] or hypoxia [15].…”

“…Polymer-based nanoparticles can be used as the carrier for numerous biologically active molecules including drugs [18], proteins [7], monoclonal antibodies [13], nucleic acids [19,20], biological extracts [16,21] and others [22]. This review will be especially concerned with the application of polymer-based nanoparticles for the treatment of various disease entities including bacterial [23,24], fungal [25] and parasitic [26] infections, ulcers [11], hypertension [12], angina [8], glaucoma [9], uveitis [27], asthma [22], cancer [15,28], neurodegenerative disease [29] and many others [30,31]. It deserves to be emphasized that several polymers are characterized by satisfying biocompatibility and predictable biodegradability [9,22] while others are non-degradable or undergo slow degradation [22,32].…”

“…It deserves to be emphasized that several polymers are characterized by satisfying biocompatibility and predictable biodegradability [9,22] while others are non-degradable or undergo slow degradation [22,32]. Remarkably, polymer-based nanoparticles can be administered orally [20,23], intravenously [18], percutaneously [30], ophthalmically [27], pulmonarily [12,25], transmucosally to nose and lungs [33] or delivered to the brain via inner ear administration [16]. It is noteworthy that selected polymers are approved by the Food and Drug Administration (FDA) to be used for therapeutic applications [27].…”

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

“…Then, the formulations were tapped 100 times mechanically by tapped density tester (ERW-SVM101201, ERWEKA, Germany) and the volumes ( 1 ) of cylinder were read to calculate the tapped density (g/mL). Furthermore, Carr's index (CI) and Hausner ratio (HR) were calculated (Varshosaz, Taymouri, & Hamishehkar, 2014) using the Eq. 3.3 and Eq.…”

“…The angle of repose (θ) is an important macroscopic parameter in evaluating the flowability of particles (Varshosaz et al, 2014) as Eq.3.5. It is the angle formed by the horizontal base and the edge of a cone-like pile of granules.…”