Abstract
The movement of micro and macro molecules into and within a cell significantly governs several of their pharmacokinetic and pharmacodynamic parameters, thus regulating the cellular response to exogenous and endogenous stimuli. Trafficking of various pharmacological agents and other bioactive molecules throughout and within the cell is necessary for the fidelity of the cells but has been poorly investigated. Novel strategies against cancer and microbial infections need a deeper understanding of membrane as well as subcellular trafficking pathways and essentially regulate several aspects of the initiation and spread of anti-microbial and anti-cancer drug resistance. Furthermore, in order to avail the maximum possible bioavailability and therapeutic efficacy and to restrict the unwanted toxicity of pharmacological bioactives, these sometimes need to be functionalized with targeting ligands to regulate the subcellular trafficking and to enhance the localization. In the recent past the scenario drug targeting has primarily focused on targeting tissue components and cell vicinities, however, it is the membranous and subcellular trafficking system that directs the molecules to plausible locations. The effectiveness of the delivery platforms largely depends on their physicochemical nature, intracellular barriers, and biodistribution of the drugs, pharmacokinetics and pharmacodynamic paradigms. Most subcellular organelles possess some peculiar characteristics by which membranous and subcellular targeting can be manipulated, such as negative transmembrane potential in mitochondria, intraluminal delta pH in a lysosome, and many others. Many specialized methods, which positively promote the subcellular targeting and restrict the off-targeting of the bioactive molecules, exist. Recent advancements in designing the carrier molecules enable the handling of membrane trafficking to facilitate the delivery of active compounds to subcellular localizations. This review aims to cover membrane trafficking pathways which promote the delivery of the active molecule in to the subcellular locations, the associated pathways of the subcellular drug delivery system, and the role of the carrier system in drug delivery techniques.
Highlights
For a cell to live, it needs a constant flow of nutrients and the removal of unwanted or used materials
In this review we have summarized some aspects of membrane trafficking and subcellular targeting phenomena
Different sub-components of drug targeting schemes have been shortly touched on and how the optimization of different drug related parameters can aid in the formulation of subcellular targeting approaches is discussed
Summary
For a cell to live, it needs a constant flow of nutrients and the removal of unwanted or used materials. The maximum therapeutic efficacy of a drug (either macromolecular or DNA, protein and peptide based drugs, oligonucleotides, siRNA etc.) can be exploited by maneuvering these with the help of some specialized carriers to various subcellular compartments like nuclear and mitochondrial targeting, to achieve safe and efficacious carriage to the desired sites of actions (Lamade et al, 2019; Nurunnabi et al, 2019; Sun et al, 2019; Wang D. et al, 2019) In this context a number of carriers have been designed, sometimes to exploit either a particular subcellular component or a drug delivery process (Huang et al, 2016).
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