Mechanistic Insight Into The Interaction Of Gastrointestinal Mucus With Oral Administration Of Nanopolymeric Carriers

Oral administration,because of its convenience,high safety and good patient compliance,has played a dominant role in pharmaceutical market for a long time.Oral drug delivery is less invasive compared to injections and this often helps improve patient compliance.However,there is a layer of mucus barrier on the surface of the gastrointestinal tract.On the one hand,it serves as a very efficient barrier that provides lubrication and regulates moisture content in the underlying tissues,and prevents harmful particles,viruses and bacteria from entering the human body.On the other hand,the protective function of the mucus also hampers the diffusion of drugs,which dramatically reduces their efficiency.Nanoparticles unable to contact with the gastrointestinal epithelial cells during the effective absorption time will be excreted in the stool with updated mucus,resulting in failed drug delivery.As such,effective interaction with gastrointestinal mucosa is crucial to the success of nanocarriers.Accordingly,in an effort to better understand the interaction of nanocarriers with gastrointestinal mucus,in this study,we synthesized diblock copolymers by ATRP method,the particle size,surface charge and hydrophilicity could be precisely controlled by adjusting the reaction parameters.The main objectives of this study were to characterize the barrier properties of gastrointestinal mucus to nanoparticulate systems and to better understand the influence of surface chemistry on particle transport through the gastrointestinal mucus barrier.In vitro and in vivo experiments were carried out to investigate the permeability of nanoparticles with different properties.The theory system of the relationship between the properties of nanoparticles and the mucous layer is formed,which provides a reference for the design of oral administration.The particle size was turned by adjusting the ratio of hydrophilic and hydrophobic copolymers segments,while zeta potential regulated by conjugating with different hydrophilic segments.1H nuclear magnetic resonance(1H NMR)spectra and GPC were characterized to confirm the synthesis of the copolymers.The size and morphology of the nanoparticles were observed by transmission electron microscope(TEM).The size of different molecular weight polymers were 150 nm,300nm,500 nm,respectively.And the potential of polymers were about +47.7m V,-2.41m V,-49.9 m V.Hydrophobicity of the copolymers was determined by measuring the contact angle.And the contact angle of hydrophobic polymer and hydrophilic polymer were 86.7° and 62.6°.The physical and chemical properties of the copolymers were indirectly revealed through the change of the particle size and the potential after the interaction between the copolymers and the mucus at 37? and 120 rpm.Besides,the permeation of copolymers in the mucus layer was studied by Transwell? chamber in vitro.In vitro and ex vivo intestinal studies were carried out to investigate the permeation of copolymers with different properties in the mucus layer.In vivo distribution was further confirmed that the basically uncharged copolymers more easily penetrate the gastrointestinal mucosa,and the hydrophobic copolymers were better on the uptake in vivo.Our study indicated that uncharged copolymers and hydrophobic copolymers exhibited great potential in gastrointestinal absorption.