Overcoming the cellular barriers and beyond: Recent progress on cell penetrating peptide modified nanomedicine in combating physiological and pathological barriers

The complex physiological and pathological conditions form barriers against efficient drug delivery.Cell penetrating peptides(CPPs),a class of short peptides which translocate drugs across cell membranes with various mechanisms,provide feasible solutions for efficient delivery of biologically active agents to circumvent biological barriers.After years of development,the function of CPPs is beyond cell penetrating.Multifunctional CPPs with bioactivity or active targeting capacity have been designed and successfully utilized in delivery of various cargoes against tumor,myocardial ischemia,ocular posterior segment disorders,etc.In this review,we summarize recent progress in CPP-functionalized nano-drug delivery systems to overcome the physiological and pathological barriers for the applications in cardiology,ophtalmology,mucus,neurology and cancer,etc.We also highlight the prospect of clinical translation of CPP-functionalized drug delivery systems in these areas.

Zwitterionic polymers:Addressing the barriers for drug delivery

Nanocarriers play an important role in drug delivery for disease treatment.However,nanocarriers face a series of physiological barriers after administration such as blood clearance,nonspecific tissue/cell localization,poor cellular uptake,and endosome trapping.These physiological barriers seriously reduce the accumulation of drugs in target action site,which results in poor therapeutic efficiency.Although polyethylene glycol(PEG)can increase the blood circulation time of nanocarriers,its application is limited due to the“PEG dilemma”.Zwitterionic polymers have been emerging as an appealing alternative to PEG owing to their excellent performance in resisting nonspecific protein adsorption.Importantly,the diverse structures bring functional versatility to zwitterionic polymers beyond nonfouling.This review focuses on the structures and characters of zwitterionic polymers,and will discuss and summarize the application of zwitterionic polymers for drug delivery.We will highlight the strategies of zwitterionic polymers to address the physiological barriers during drug delivery.Finally,we will give some suggestions that can be utilized for the development of zwitterionic polymers for drug delivery.This review will also provide an outlook for this field.Our aim is to provide a comprehensive and systemic review on the application of zwitterionic polymers for drug delivery and promote the development of zwitterionic polymers.

MASS TRANSPORT IN SOLID TUMORS (Ⅰ)──FLUID DYNAMICS

A three-porous-medium model for transvascular exchange and extravascular transport of fluid and macromolecules in a spherical solid tumor is developed. The microvasculature , lymphatics, and tissue space are each treated as a porous medium with the flow of blood. lymph, and interstitial fluid obeying Darcy's law and Starling 's assumption. In this part, the role of interstitial pressure and fluid convection are studited. The analytical soiutions are obtained for foe isolated tumor and the normal-tissue-surrounded tumor respectively. The calculated interstitial pressure profue are consistent with the experimental observation that the elevated interstitial pressure is a major barrier in the penetration of macromolecular drug into tumors. The factors which may reduce the interstitial pressure are analyzed in details.

Oral delivery of polyester nanoparticles for brain-targeting: Challenges and opportunities

Efficient oral delivery of drugs treating brain diseases has long been a challenging topic faced by the drug delivery community. Fortunately, polyester nanoparticles offer certain solutions to this problem. This review article firstly describes the main obstacles faced by oral administered brain targeting, including:(1)instability in the gastrointestinal tract;(2) poor penetration of the intestinal mucosa and epithelium;(3)blood clearance;and(4) restriction by the BBB. Then the key factors influencing brain-targeting efficiency of orally administered polyester nanoparticles are also discussed, such as size, shape and surface properties. Finally, recent brain-targeting delivery strategies using oral polyester nanoparticles as carriers and their effects on brain drugs transport are reviewed, and the delivery ‘as a whole’ strategy of polyester nanoparticles will provide new insight for oral brain-targeting delivery. And by combination of multiple strategies, both the stability and permeability of polyester nanoparticles can be greatly improved for oral brain drug delivery.