Abstract
The efficient noninvasive treatment of neurodegenerative disorders is often constrained by reduced permeation of therapeutic agents into the central nervous system (CNS). A vast majority of bioactive agents do not readily permeate into the brain tissue due to the existence of the blood-brain barrier (BBB) and the associated P-glycoprotein efflux transporter. The overexpression of the MDR1 P-glycoprotein has been related to the occurrence of multidrug resistance in CNS diseases. Various research outputs have focused on overcoming the P-glycoprotein drug efflux transporter, which mainly involve its inhibition or bypassing mechanisms. Studies into neurodegenerative disorders have shown that the P-glycoprotein efflux transporter plays a vital role in the progression of schizophrenia, with a noted increase in P-glycoprotein function among schizophrenic patients, thereby reducing therapeutic outcomes. In this review, we address the hypothesis that methods employed in overcoming P-glycoprotein in cancer and other disease states at the level of the BBB and intestine may be applied to schizophrenia drug delivery system design to improve clinical efficiency of drug therapies. In addition, the current review explores polymers and drug delivery systems capable of P-gp inhibition and modulation.
Highlights
The effectiveness of drug treatments for numerous disease states such as cancer, infectious diseases, and central nervous system (CNS) disorders is limited by poor therapeutic outcomes or drug resistance
Treatment outcomes associated with schizophrenia therapy are reduced due to pharmacoresistance, which leads to a reduction in patient compliance
The P-glycoprotein (P-gp) efflux transporter located within the blood-brain barrier restricts the uptake of drugs and other molecules within the CNS; it has been implicated in the occurrence of pharmacoresistant schizophrenia
Summary
The effectiveness of drug treatments for numerous disease states such as cancer, infectious diseases, and central nervous system (CNS) disorders (epilepsy, depression, and schizophrenia) is limited by poor therapeutic outcomes or drug resistance. P-gp is a membrane transporter of the ABC superfamily located within both the intestinal epithelium and the BBB playing a dynamic role in the bioavailability of orally administered drugs employed in the treatment of neurodegenerative disorders [7]. The amorphous form alternatively tends to improve the dissolution rate and solubility significantly compared to its crystalline form which increases the rate and degree of oral absorption [29] Apart from these mechanisms, the small intestine has the ability to metabolize drugs via a diversity of pathways involving phase I and phase II reactions, which in turn may cause a restriction in oral bioavailability. CYP3A4 is the most abundant cytochrome P450 enzyme within the intestinal enterocytes that is implicated in the metabolic elimination of many drugs [29]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
