Drug Delivery Approaches
Modern Advances in Pharmaceutical Research Vol. 2,
Page 1-30
Abstract
This review discusses the different biological barriers that affect the delivery of therapeutic agents through membranes, such as intestinal mucosa, Brain Blood Barrier (BBB), and mediators of transport such as efflux transporters and the approaches for overcoming such barriers. The approaches illustrated in this review include: utilizing natural occurring transporters to deliver drugs specifically to their targets, nucleoside analogues delivery, CYP-activated prodrugs that target drugs to the liver, modification of passive diffusion by efflux pumps, intestinal transporters such as PEPT1 and GLUT1, Carrier Mediated Transport (CMT) systems for transporting nutrients, vitamins or hormones into the central nervous system, tissue selective drug delivery, administration of an exogenous enzyme to reach the tumor site which is followed by systemic administration of non-toxic prodrugs (ADEPT, GDEPT and VDEPT), enzymes involve in the bioconversion of ester-based prodrugs for activation (hydrolysis) of prodrugs to their active forms, brain targeted Chemical Delivery Systems (CDS), amino acid prodrugs to improve oral bioavailability, sustained drug delivery and intravenous drug delivery. Furthermore, Receptor-Mediated Transcytosis (RMT) for efficacious delivery of Nano particles via the intestinal mucosa and BBB, and the prodrug chemical approach based on intra molecularity to deliver anti-cancer drugs is discussed.
Graphical Abstract
Conversion of the cyclic peptide prodrug to the parent peptide by the action of esterase enzymes
Keywords:
- Drug delivery
- prodrugs
- tumor targeting
- computational approaches
- enzymes targeting
- acyclovir
- codrugs
- CYP-activated prodrugs
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