Surface-Modified PLGA Nanoparticles for Targeted Drug Delivery to Neurons

Abstract

The major challenge for the treatment of neuronal diseases is the inability of therapeutic moieties to cross the blood–brain barrier (BBB) and nasal mucosal barrier. The therapeutic moieties for the treatment of brain diseases lack targeting due to its non-specificity toward receptors located at BBB and Pgp efflux mechanism. This results in impeding its ability to reach to maximum effective concentration. Many of these therapeutic moieties possess dose-limiting systemic side effects which along with complex dosage regimens hinder patient compliance and result in discontinuation of treatment. A number of drug delivery and drug-targeting systems have been investigated to increase drug bioavailability and the fraction of the drug accumulated in the targeted area, in order to minimize drug degradation and loss, as well as to reduce harmful side effects. Among all, PLGA NPs have been achieved fascinating properties as a carrier system owing to its biodegradable, biocompatible, and easy functionalization properties. Most importantly PLGA is available in various ratios which can be helpful for tuning the entrapment/loading of therapeutic moieties in NPs. Intranasal delivery has come to the forefront as a method that can bypass the BBB and target drugs directly to the brain as an alternative to invasive methods. The objective of this chapter is to provide a broad overview on current strategies for brain drug delivery and its applications. It is hoped that this chapter could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB and intranasal route in both healthy and pathological conditions, this chapter revisits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Furthermore, in this chapter, various conjugation strategies for attaching targeting moieties to the surface of nanocarrier have been included. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using noninvasive techniques to enhance brain drug uptake.