Abstract
Research has increasingly focused on the delivery of high, often excessive amounts of drugs, neglecting negative aspects of the carrier’s physical preconditions and biocompatibility. Among them, little attention has been paid to “small but beautiful” design of vehicle and multiple cargo to achieve effortless targeted delivery into deep tissue. The design of small biopolymers for deep tissue targeted delivery of multiple imaging agents and therapeutics (mini-nano carriers) emphasizes linear flexible polymer platforms with a hydrodynamic diameter of 4 nm to 10 nm, geometrically favoring dynamic juxtaposition of ligands to host receptors, and economic drug content. Platforms of biodegradable, non-toxic poly(β-l-malic acid) of this size carrying multiple chemically bound, optionally nature-derived or synthetic affinity peptides and drugs for a variety of purposes are described in this review with specific examples. The size, shape, and multiple attachments to membrane sites accelerate vascular escape and fast blood clearance, as well as the increase in medical treatment and contrasts for tissue imaging. High affinity antibodies routinely considered for targeting, such as the brain through the blood–brain barrier (BBB), are replaced by moderate affinity binding peptides (vectors), which penetrate at high influxes not achievable by antibodies.
Highlights
Mini-nano carriers are designed with properties that are shared with low molecule pharmaceutics and full-sized, usually encapsulating nanoparticles
Mini-nano carriers are macromolecules designed to penetrate into the brains of healthy mice and mouse models of Alzheimer’s disease and glioblastoma by transcytosis pathways of selected peptide vectors: angiopep-2 (AP2) vector of the lipoprotein receptor-related protein-1 (LRP-1) pathway [72,73], cTfRL-peptide [39] and B6-peptide vectors of the
Presented above are several cases of mini-nano devices that function as vehicles across normal and tumor (BBB) barriers performing high-grade delivery, imaging, and antitumor treatment
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The invention of nanometer-scale drug delivery was motivated by the possibility of accumulating high drug concentrations at diseased sites through targeted delivery This approach should facilitate the destruction of pathological cells, tissues or organs while leaving healthy regions of the body unaffected [1] (Figure 1a). High drug loads carry the risk of side effects (especially in the absence of targeting), excess drug leakage into healthy tissues, cytotoxicity of the carrier or its degradation andMass development of storage disease owing have to aggrethrough receptor gated products, bio barriers. Designed to increase delivery, especially when flux (mass delivered per unit time) across a bio barrier is low Nano capsules such as liposomes, micelles, and sponge-like solid nanoparticles are frequently used as agent carriers [2,3,4] (Figure 1c).
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