Jul 2026· International journal of pharmaceutics· Vol 702, pp.
127176
· 1 citation· 335 references
Medicine
TL;DR
This review summarizes the design principles, biological barriers, formulation challenges, and translational considerations that govern polymeric peptide and protein delivery and identifies those that integrate protein stability, controlled exposure, patient usability, robust manufacturing, validated analytics, and regulatory clarity into a coherent product-development framework.
Abstract
Peptides and proteins have become central to modern therapeutics because of their high biological specificity and ability to modulate targets that are often inaccessible to small molecules. However, their clinical use remains constrained by molecular instability, enzymatic degradation, rapid systemic clearance, poor epithelial permeability, immunogenicity risk, and the practical burden of repeated parenteral administration. Polymeric delivery systems offer versatile strategies to address these limitations through molecular conjugation, biodegradable depots, nanoparticles, micelles, hydrogels, nanogels, mucoadhesive systems, and microneedle-based platforms. This review summarizes the design principles, biological barriers, formulation challenges, and translational considerations that govern polymeric peptide and protein delivery. Particular emphasis is placed on polymer-cargo interactions, stability preservation, controlled release versus polymer degradation, critical quality attributes, safety, immunogenicity, manufacturability, and regulatory complexity. Clinically mature examples, including PEGylated proteins and PLGA/PLA-based long-acting depots, demonstrate that polymeric technologies can improve pharmacokinetics and dosing convenience when the delivery objective is clearly defined and product complexity remains manageable. In contrast, many nanoscale, mucosal, and stimuli-responsive systems remain limited by weak in vitro-in vivo translation, incomplete characterization of released cargo bioactivity, scale-up difficulty, and uncertain regulatory pathways. Future progress will require development strategies that begin with clinical need and target product profile rather than platform novelty alone. Successful polymeric systems are likely to be those that integrate protein stability, controlled exposure, patient usability, robust manufacturing, validated analytics, and regulatory clarity into a coherent product-development framework.
This review presents a unified innovation framework that integrates upstream molecular engineering strategies including cyclization, peptide stapling, D- and β-amino acid substitution, PEGylation, and backbone modification with downstream advanced delivery platforms such as nanocarriers, microneedles, self-assembling hydrogels, and stimuli-responsive systems, while also addressing critical translational considerations including scalability, regulatory requirements, and manufacturing consistency.
Pradip Karale, Saloni Borse, Anjali Gavit et al.· Journal of Pharmaceutical In...· 0 citations
Nanoparticle-based drug delivery systems have become an important component of modern nanomedicine, enabling improved drug protection, controlled release, targeted delivery, and the modulation of pharmacokinetic behavior. Their therapeutic performance is governed by physicochemical properties such as size, shape, surface chemistry, and material composition, which influence biological interactions, biodistribution, cellular uptake, and clearance. This review examines major nanoparticle platforms, including polymeric, lipid-based, inorganic, carbon-based, and hybrid systems, together with passive and active targeting and endogenous and externally triggered release strategies. Current and emerging applications in oncology, infectious diseases, central nervous system disorders, gene therapy, and vaccines are discussed alongside theranostic and combination-delivery approaches. Particular emphasis is placed on computational modeling, artificial intelligence, and digital twins for formulation optimization and personalized nanomedicine. Key barriers to clinical translation, including manufacturing scalability, biological variability, limitations of EPR-mediated targeting, regulatory standardization, and long-term safety, are critically evaluated. Finally, emerging directions in sustainable nanomanufacturing and biomimetic delivery are discussed. By integrating biological mechanisms with computational, manufacturing, regulatory, and clinical considerations, this review provides a translational perspective on advancing nanoparticle drug-delivery systems from laboratory development toward clinical implementation.
Subin Antony Jose, Benjamin Crutchfield, M. Caballero et al.· Molecules· 0 citations
A structured translational roadmap is proposed that prioritizes biologically predictive design, fit-for-purpose safety assessment, scalable good manufacturing practice production, early regulatory alignment, and clinically meaningful benefit over unnecessary structural complexity.
Yi Li, Rui Luo, Yuxuan Li et al.· Biomedicine & pharmacotherap...· 0 citations
The combination of polymeric materials and prodrug chemistry has reformed drug delivery by presenting specific, precise, and targeted therapeutic release. This review provides the informations on progresses in polymeric materials for prodrug design, focusing on their importance in improving bioavailability, pharmacokinetics, and site-specific activation. Polymers play role as dedicated carriers that enhance solubility, stability, and biocompatibility while shortening toxicity. Novel polymeric designs, such as stimuli responsive micelles, nanogels, and amphiphilic conjugates coordinated release as a response to the stimuli: pH, enzyme, or redox potential gradient, mostly in cancer and inflammatory disease therapy. Prodrug approaches including carrier-linked, bio-precursor, and site-specific designs are deliberated in light of enzyme-activated, photo, and radiotherapy responsive systems. Challenges persist in large scale synthesis, clinical translation, and patient specific differences. Impending directions highlight the merging of artificial intelligence, regenerative medicine, and bioorthogonal chemistry to create personalized and multifunctional polymer-prodrug delivery systems that can significantly boost therapeutic precision.
Therapeutic glycoproteins, a pivotal class of biopharmaceuticals, have transformed modern medicine through their broad applications in oncology, immunotherapy, and infectious disease management. Their structural complexity and biological specificity make them highly effective in targeting disease pathways; however, challenges related to stability, bioavailability, and delivery efficacy limit their full potential. Recent advancements in delivery technologies have sought to address these challenges through innovative approaches such as nanotechnology-based carriers, controlled-release systems, and molecular engineering. These strategies have demonstrated the ability to enhance glycoprotein stability, optimize pharmacokinetics, and achieve targeted delivery with minimal off-target effects. This review provides a comprehensive overview of state-of-the-art lipid-based delivery systems specifically designed to overcome the unique pharmaceutical challenges associated with therapeutic glycoproteins, highlighting their design principles, formulation strategies, mechanisms of encapsulation and release, and therapeutic advantages in improving glycoprotein stability, bioavailability, targeted delivery, and treatment efficacy. In addition to surveying the current landscape, this review delves into the key challenges impeding the widespread adoption of advanced delivery systems, including immunogenicity, manufacturing scalability, and clinical translation. The review concludes with insights into emerging trends in the development of lipid-based delivery systems, positioning glycoprotein therapeutics at the forefront of innovation in biopharmaceuticals. This overview of advancements and challenges aims to provide a roadmap for future progress in the field of glycoprotein delivery and therapeutic applications.
Hamad Alrbyawi· Pharmaceutics· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
