Nanocarrier Fabrication and Macromolecule Drug delivery: Challenges and Opportunities

Abstract

Macromolecules (proteins/peptides) have the potential for the development of new therapeutics. Due to their specific mechanism of action, macromolecules can be administered at relatively low doses compared with small-molecule drugs. Unfortunately, the therapeutic potential and clinical application of macromolecules is hampered by various obstacles including their large size, short in vivo half-life, phagocytic clearance, poor membrane permeability and structural instability. These challenges have encouraged researchers to develop novel strategies for effective delivery of macromolecules. In this review, various routes of macromolecule administration (invasive/noninvasive) are discussed. The advantages/limitations of novel delivery systems and the potential role of nanotechnology for the delivery of macromolecules are elaborated. In addition, fabrication approaches to make nanoformulations in different shapes and sizes are also summarized.

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

“…Although the defined size ranges for microparticles (MPs) and nanoparticles (NPs) can differ based on convention and sources [43], NPs will be referred to particles within the nanometer scale (1–1000 nm) and MPs as particles in the micrometer scale (1–1000 µm) for the purpose of discussing pharmaceutical carrier formulations in this review, NPs and MPs have a variety of physicochemical properties, such as size, surface area, shape, molecular weight, porosity, hydrophobicity and charge, that allow modifications and functionalization to suit a wide range of macromolecules (Figure 4B) [24,44]. These carriers offer high loading capacity, protection from enzymes resulting in improved macromolecule stability with enhanced lung distribution and retention.…”

“…For example, surface coating or functionalization improves the pharmacokinetics; particle shielding with lipids or hydrophilic polymers as polyethylene glycol (PEG) lowers the macrophages uptake and recognition, mucoadhesive particles increase the lung retention, i.e. chitosan, coating of carriers with active targeting ligands such as antibodies will be discussed later [44]. A study showed a promising PEG-co-polyester MPs delivery system, composed of co-block polymer poly(glyceroladipate-co-ω-pentadecalactone) incorporating PEG within the polymer chain, as a suitable carrier for α-chymotrypsin, a mucolytic enzyme, demonstrating high loading efficiency, retention of enzyme activity and suitability for DPI  [48].…”

“…They have improved physicochemical properties based on biocompatible and biodegradable polymers. Uniform size with low polydispersity, stability, versatile ability for modifications, and amine group-transfection ability enhances their carrier properties [44,54]. However, the complex formulations with multifaceted steps to access the core and build branches are limiting factors.…”

“…They can be formulated from natural or synthetic lipids mostly with neutral or anionic charge such as phosphatidylcholines, sphingomyelins, phosphatidylglycerols, and phosphatidylinositols [44]. However, cationic liposomes are produced using lipids with a positive charge and are used for gene delivery due to their capability for ionic interactions with DNA, siRNA/miRNA [24,44]. They form single bilayer or multilayers that can be used for the controlled release, encapsulate hydrophilic/lipophilic active agents, and improve loading capacity, versatile chemical functionalization, and active targeting.…”

Next generation drug delivery: circulatory cells-mediated nanotherapeutic approaches

“…Nanocarriers (NCs), such as liposomes, hydrogels, nanoparticles, micelles, fibers, and dendrimers, provide several advantages in delivery applications and have been extensively applied to enhance the therapeutic efficacy of drugs [1][2][3][4]. However, the major challenges in NC applications are to transport the therapeutics to the target site without significant degradation, avoid rapid phagocytic clearance, prolonging the circulation time, insufficient targeting, and limited ability to cross biological barriers such as the blood-brain barrier [1][2][3][4].…”