Polymer-based nanocarriers to transport therapeutic biomacromolecules across the blood-brain barrier DOI Creative Commons
Elena Romero‐Ben, Upashi Goswami, Javier Cruz

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Therapeutic biomacromolecules such as genetic material, antibodies, growth factors and enzymes represent a novel therapeutic alternative for neurological diseases disorders. In comparison to traditional therapeutics, which are mainly based on small molecular weight drugs that address the symptoms of these disorders, can reduce undesired side effects target specific pathological pathways, thus paving way towards personalized medicine. However, undergo degradation/denaturation processes in physiological environment show poor capacity cross blood-brain barrier (BBB). Consequently, they rarely reach central nervous system (CNS) their active form. Herein, we critically overview several polymeric nanocarriers protect deliver across BBB. Polymeric first categorized architecture (biodegradable solid nanoparticles, nanogels, dendrimers, self-assembled nanoparticles), ultimately determines physico-chemical properties function. The available formulations then thoroughly analyzed, placing particular attention those strategies ensure stability during encapsulation process promote passage BBB by controlling physical (e.g., mechanical properties, size, surface charge) chemical functional groups, targeting motifs) properties. Accordingly, this review gives unique perspective delivery BBB, representing concise, complete easy-to-follow guide, will be high interest chemists, material scientists, pharmacologists biologists. Besides, it also provides critical about limited clinical translation systems. STATEMENT OF SIGNIFICANCE: increasing incidence disorders is major health concern. use has been placed spotlight many investigations. reaching concentration levels restricted and, thus, represents main challenge when developing efficient therapies. provide discussion into system, highlighting potential future directions overcome current challenges.

Language: Английский

PEGylated therapeutics in the clinic DOI Creative Commons
Yongsheng Gao, Maithili Joshi, Zongmin Zhao

et al.

Bioengineering & Translational Medicine, Journal Year: 2023, Volume and Issue: 9(1)

Published: Sept. 22, 2023

The covalent attachment of polyethylene glycol (PEG) to therapeutic agents, termed PEGylation, is a well-established and clinically proven drug delivery approach improve the pharmacokinetics pharmacodynamics drugs. Specifically, PEGylation can parent drug's solubility, extend its circulation time, reduce immunogenicity, with minimal undesirable properties. technology has been applied various modalities including small molecules, aptamers, peptides, proteins, leading over 30 PEGylated drugs currently used in clinic many investigational agents under clinical trials. Here, we summarize diverse types strategies, key advantages therapeutics their drugs, broad applications impacts settings. A particular focus given size, topology, functionalities PEG molecules utilized as well those An additional section dedicated analyzing some representative that were discontinued at different stages studies. Finally, critically discuss current challenges faced development translation agents.

Language: Английский

Citations

75
Mechanisms and Barriers in Nanomedicine: Progress in the Field and Future Directions DOI
Thomas J. Anchordoquy, Natalie Artzi, Irina V. Balyasnikova

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(22), P. 13983 - 13999

Published: May 20, 2024

In recent years, steady progress has been made in synthesizing and characterizing engineered nanoparticles, resulting several approved drugs multiple promising candidates clinical trials. Regulatory agencies such as the Food Drug Administration European Medicines Agency released important guidance documents facilitating nanoparticle-based drug product development, particularly context of liposomes lipid-based carriers. Even with achieved, it is clear that many barriers must still be overcome to accelerate translation into clinic. At conference workshop "Mechanisms Barriers Nanomedicine" May 2023 Colorado, U.S.A., leading experts discussed formulation, physiological, immunological, regulatory, clinical, educational barriers. This position paper invites open, unrestricted, nonproprietary discussion among senior faculty, young investigators, students trigger ideas concepts move field forward.

Language: Английский

Citations

24
Engineering LNPs with polysarcosine lipids for mRNA delivery DOI Creative Commons

Diana D. Kang,

Xucheng Hou, Leiming Wang

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 37, P. 86 - 93

Published: March 16, 2024

Since the approval of lipid nanoparticles (LNP)-mRNA vaccines against SARS-CoV-2 virus, there has been an increased interest in delivery mRNA through LNPs. However, current LNP formulations contain PEG lipids, which can stimulate generation anti-PEG antibodies. The presence these antibodies potentially cause adverse reactions and reduce therapeutic efficacy after administration. Given widespread deployment COVID-19 vaccines, exposure to may necessitate evaluation alternative without components. In this study, we investigated a series polysarcosine (pSar) lipids as alternatives determine whether pSar could still provide functionality ALC-0315 SM-102 systems. We found that complete replacement with increase or maintain efficiency exhibit similar safety profiles vivo.

Language: Английский

Citations

16
Pegylated solid lipid nanoparticles for the intranasal delivery of combination antiretroviral therapy composed of Atazanavir and Elvitegravir to treat NeuroAIDS DOI

Arya Bazargani,

Mohammad Hejazi, Matthew Fernandez

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 670, P. 125166 - 125166

Published: Jan. 5, 2025

Language: Английский

Citations

4
Emerging strategies for nanomedicine in autoimmunity DOI
Ajay S. Thatte, Margaret M. Billingsley, Drew Weissman

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 207, P. 115194 - 115194

Published: Feb. 10, 2024

Language: Английский

Citations

9
A journey through the history of PEGylated drug delivery nanocarriers DOI Creative Commons
Ana M. López-Estévez, Ruxandra Gref, Marı́a José Alonso

et al.

Drug Delivery and Translational Research, Journal Year: 2024, Volume and Issue: 14(8), P. 2026 - 2031

Published: May 25, 2024

Abstract This note aims to inspire through providing a personal view of the development and potential Drug Delivery Nanocarriers functionalized with polythyleneglycol (PEG). polymer has been used extensively in Pharmaceutical Technology variety compositions, including polyethylene oxide (PEO)-based surfactants. However, concept PEGylation, which started 70’s, differs from functionality surfactant, already discloses 50’s. Here, we strictly adhere biological PEGylated nanocarriers intended have reduced interaction proteins and, therefore, modify their biodistribution as well facilitate diffusion across mucus other barriers. We analyze how this evolved over years benefit obtained so far terms marketed nanomedicines provide readers prospect topic.

Language: Английский

Citations

9
Advancing Therapeutic Strategies with Polymeric Drug Conjugates for Nucleic Acid Delivery and Treatment DOI Creative Commons
Aftab Ullah,

Marina Khan,

Yibang Zhang

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 25 - 52

Published: Jan. 1, 2025

Abstract: The effective clinical translation of messenger RNA (mRNA), small interfering (siRNA), and microRNA (miRNA) for therapeutic purposes hinges on the development efficient delivery systems. Key challenges include their susceptibility to degradation, limited cellular uptake, inefficient intracellular release. Polymeric drug conjugates (PDCs) offer a promising solution, combining benefits polymeric carriers agents targeted treatment. This comprehensive review explores nucleic acid therapeutics, focusing conjugates. It investigates how these address obstacles, enhance systemic circulation, reduce immunogenicity, provide controlled release, improving safety profiles. delves into conjugation strategies, preparation methods, various classes PDCs, as well strategic design, highlighting role in delivery. Applications PDCs treating diseases such cancer, immune disorders, fibrosis are also discussed. Despite significant advancements, adoption persist. concludes with insights future directions this transformative technology, underscoring potential advance acid-based therapies combat infectious significantly. Keywords: polymer conjugates,

Language: Английский

Citations

1
Nanostructured Drug Delivery Systems in Immunotherapy: An Updated Overview of Nanotechnology-Based Therapeutic Innovations DOI Creative Commons

George-Alexandru Croitoru,

Adelina-Gabriela Niculescu,

Dragoș Epistatu

et al.

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(19), P. 8948 - 8948

Published: Oct. 4, 2024

Using nanostructured drug delivery systems has attracted increasing interest in immunotherapeutic approaches. The intrinsic immunomodulatory properties and versatility of nanoparticles used as carriers were consistently reported to augment treatment efficiency nanoscaled materials increase accumulation at the desired site, enhance cell internalization, improve therapeutic outcomes. Thus, numerous studies have exploited potential use vehicles delivering different cargo a promising alternative for treating conditions like cancer, autoimmune diseases, infectious allergic immune disorders. In this context, paper presents solid basis innovations, highlighting their advantages improving strategies, reviewing clinical applications, discussing existing challenges ways overcome them.

Language: Английский

Citations

8
Approved delivery strategies for biopharmaceuticals DOI
Makhloufi Zoulikha, Zhongjian Chen, Jun Wu

et al.

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: 36(2), P. 110225 - 110225

Published: July 8, 2024

Language: Английский

Citations

7
Improving the pharmacokinetics, biodistribution and plasma stability of monobodies DOI Creative Commons

Adrian Valentin Dinh-Fricke,

Oliver Hantschel

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 4, 2024

Cancer is a leading cause of death worldwide. Several targeted anticancer drugs entered clinical practice and improved survival cancer patients with selected tumor types, but therapy resistance metastatic disease remains challenge. A major class are therapeutic antibodies, their use limited to extracellular targets. Hence, alternative binding scaffolds have been investigated for intracellular better tissue penetration. Among those, monobodies small synthetic protein binders that were engineered bind high affinity selectivity central oncoproteins inhibit signaling. Despite as basic research tools, the potential therapeutics be explored. In particular, pharmacological properties monobodies, including plasma stability, toxicity pharmacokinetics not investigated. Here, we show well-tolerated in mice, short half-life vivo due rapid renal clearance. Therefore, monobody fusions an albumin-binding domain (ABD), which showed enhanced without affecting target binding: We found ABD-monobody display increased stability mouse plasma. Most importantly, ABD-monobodies dramatically prolonged rapidly excreted by clearance, remaining blood significantly longer, while accumulating specific internal organs. Our results demonstrate promise versatility developed into future treatment. anticipate may able extend spectrum targets, resulting significant benefit patient outcome.

Language: Английский

Citations

6