Current Update on Transcellular Brain Drug Delivery

Abstract

It is well known that the presence of a blood–brain barrier (BBB) makes drug delivery to the brain more challenging. There are various mechanistic routes through which therapeutic molecules travel and deliver the drug across the BBB. Among all the routes, the transcellular route is widely explored to deliver therapeutics. Advances in nanotechnology have encouraged scientists to develop novel formulations for brain drug delivery. In this article, we have broadly discussed the BBB as a limitation for brain drug delivery and ways to solve it using novel techniques such as nanomedicine, nose-to-brain drug delivery, and peptide as a drug delivery carrier. In addition, the article will help to understand the different factors governing the permeability of the BBB, as well as various formulation-related factors and the body clearance of the drug delivered into the brain.

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs

“…Addressing the characteristic challenges of poorly soluble drugs, our analysis of nanonization techniques, surface modification technologies, and carrier-mediated tactics concludes that NDDS can precisely enhance the solubility of these drugs. Nanonization techniques break through biological barriers like the blood-brain barrier and nasal transport barriers, thereby improving drug delivery efficiency 101 , 102 and introducing new administration routes. Surface modification, altering the physicochemical properties of nanoparticle surfaces, enhances cellular targeting and consequently drug utilization.…”

“…These systems are increasingly applied in clinical settings, extensively used for delivering chemotherapeutics, phototherapeutic agents, and cancer vaccines. 102 For instance, Wang et al 103 noted that nano-formulations wrapped in macrophage-cancer cell hybrid membranes exhibit superior immune evasion and homotypic adhesion, enabling prolonged in vivo retention and targeted accumulation, significantly inhibiting the growth of colorectal cancer cells. Hence, biomimetic nano delivery systems demonstrate extensive application potential in cancer treatment and management, heralding a promising future.…”

Neuroprotective Peptides and New Strategies for Ischemic Stroke Drug Discoveries

“…A useful property of peptides is their ability to overcome the BBB, which allows them to be used as a carrier for drug delivery. Brainpermeable peptide-drug conjugates, consisting of BBB shuttle peptides, linkers, and drug molecules, directly cross the BBB via an adsorption-mediated transcytosis pathway or through interaction with receptors or other proteins on the surfaces of BBB cells to initiate endogenous transcytosis or other means of transport [62][63][64].…”

Non-Invasive Drug Delivery across the Blood–Brain Barrier: A Prospective Analysis

“…Figure 4 lists several approaches to noninvasive deliveries. Transcellular (drug delivery via cells) and paracellular (drug delivery between adjacent cells) are the two main routes that frequently carry drugs to the brain [78]. Ions and solutes passively diffuse across the BBB via the paracellular pathway, which concentration gradients facilitate.…”