Abstract
Over the last three decades, proteins and peptides have attracted great interest as drugs of choice for combating a broad spectrum of diseases, including diabetes mellitus, cancer, and infectious and neurological diseases. However, the delivery of therapeutic proteins to target sites should take into account the obstacles and limitations related to their intrinsic sensitivity to different environmental conditions, fragile tertiary structures, and short half-life. Polymeric nanostructures have emerged as competent vehicles for protein delivery, as they are multifunctional and can be tailored according to their peculiarities. Thus, the enhanced bioavailability and biocompatibility, the adjustable control of physicochemical features, and the colloidal stability of polymer-based nanostructures further enable either the embedding or conjugation of hydrophobic or hydrophilic bioactive molecules, which are some of the features of paramount importance that they possess and which contribute to their selection as vehicles. The present review aims to discuss the prevalent nanostructures composed of block copolymers from the viewpoint of efficient protein hospitality and administration, as well as the up-to-date scientific publications and anticipated applications of polymeric nanovehicles containing proteins and peptides.
Highlights
Since human insulin was approved by the FDA (Food and Drug Administration) in1982, when it became the first commercially available recombinant therapeutic protein [1], several therapeutic proteins and peptides have been endorsed for clinical use and others are under development for the therapy of various diseases such as cancer [2], hepatitis [3], and diabetes [4,5]
The physicochemical studies demonstrated the QPDMAEMA-b-PLMA-b-POEGMA/insulin complexes were colloidally stable under all insulin concentrations utilized, whereas insulin conformation was not affected by the complexation process with the cationic triblock terpolymer micelles, indicating that these nanoformulations can be applied for insulin delivery
Therapeutic proteins and peptides exhibit a plethora of advantages that cannot be ignored; they have attracted considerable attention for use in combating various chronic diseases such as diabetes, cancer, and neurological or infectious diseases
Summary
1982, when it became the first commercially available recombinant therapeutic protein [1], several therapeutic proteins and peptides have been endorsed for clinical use and others are under development for the therapy of various diseases such as cancer [2], hepatitis [3], and diabetes [4,5]. The high molecular weight of proteins and peptides in conjunction with their varying surface charges and fragile tertiary structures contribute to their limitations in their use as drug molecules, as the capability of their stand-alone delivery into the intracellular space is limited [12] Their high hydrophilicity and the presence of charged groups subsequently lead to poor cell membrane permeability. Regarding the complexity of therapeutic protein and peptide delivery, the field of nanotechnology has effectively bridged the gap, as it provides several nanoscale systems that have the required encapsulating properties, further offering a better pharmacokinetic profile [18,19] Such nanosystems include lipid nanoparticles [20], liposomes [21], polymeric nanoparticles [22], and magnetic nanoparticles [23], among others. In vitro, in vivo, and current pharmaceutical applications over the last five years are reported
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