RESUMEN
Nicotine in mainstream cigarette smoke is predominantly present in the particulate phase. Interestingly, however, the deposition efficiency of smoke particles in the respiratory tract is less effective than is the nicotine retention. In the literature, four nicotine deposition mechanisms are identified: (a) direct gas deposition, (b) evaporative gas deposition, (c) particle deposition with evaporation, and (d) particle deposition with diffusion. In this article we present a physically motivated fundamental model to address nicotine deposition mechanisms (b) and (c) from the vapor phase. The model incorporates nicotine mass transport through estimates for the diffusion time across the epithelial layer and the time for nicotine vapor diffusion from the gas volume to the tissue surfaces in the tracheobronchial and pulmonary regions of the respiratory tract. The model comprises four mass transfer processes for nicotine at the surface of the respiratory tract epithelium: (1) conversion of free base nicotine from protonated nicotine; (2) free base nicotine transport across the epithelium; (3) free base nicotine evaporation; and (4) diffusion of free base nicotine vapor from the surface gas layer into the airway lumen. Results of the nicotine mass transport model suggest that the principal mechanism of nicotine delivery to the lung is by direct deposition of particles to the alveolar fluid lining, followed rapidly by evaporation into the lumen and then gas diffusion back to the surface as nicotine depletes in the surface layer through its transport across the epithelium.
Asunto(s)
Estimulantes Ganglionares/farmacocinética , Pulmón/metabolismo , Nicotina/farmacocinética , Sistema Respiratorio/metabolismo , Transporte Biológico , Bronquios/metabolismo , Humanos , Exposición por Inhalación , Modelos Biológicos , Alveolos Pulmonares/metabolismo , Tráquea/metabolismoRESUMEN
Nicotine's dose and rate of delivery to the brain play an important role in its addiction and cardiovascular effects. Nicotine is mainly present in the particulate phase of cigarette smoke, and since particle size distribution controls the deposition behavior of particles in the respiratory tract, changes in the particle size distribution can produce variations in its regional and total dose to the lung. These variations can change its absorption rate and delivery to the brain. The particle size distribution of mainstream smoke (MS) varies with changes in puffing regimen and cigarette design and composition. This study examined nicotine in different particle size fractions of MS generated from 2R4F, Marlboro Medium, and Quest1 cigarettes using 3 puffing regimens: (1) FTC-like puff, 35 ml over 2 s; (2) short puff, 50 ml over 2 s; and (3) long puff, 100 ml over 10 s. MS was generated in a chamber at 37 degrees C and >95% relative humidity (RH), and size-segregated particles were collected using RJR cascade impactors. Particle size distribution was determined by spectrophotometry. Nicotine was analyzed using gas chromatography and mass spectrometry. Results showed that nicotine speciates in larger particles (1.1-1.9 microm diameter) under the long puffing regimen and in smaller particles (0.4-1.1 microm diameter) under the short puffing regimen, while mass median aerodynamic diameter of mainstream smoke particles was found to be approximately constant (0.9-1.0 microm) for the three puffing regimens. Overall, changes in puffing regimen have a significant effect on particle size distribution of nicotine and its deposited dose.