Modified-Release Pulmonary Delivery Systems for Labile Bioactives: Design, Development, and Applications

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 470 - 470

Published: April 3, 2025

Pulmonary delivery of bioactives has shown to be a promising route for the treatment respiratory conditions, however, numerous physiological barriers, such as mucociliary clearance and immune responses, pose significant hurdles efficacy. These barriers specifically affect labile mRNA, peptides, proteins, probiotics, which are susceptible degradation due prevailing conditions. Various drug platforms have been developed address these challenges, including, among others, polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles that encapsulate protect during formulation administration, enabling improved bioavailability, sustained release, enhanced stability, while further modification allows targeted delivery. This review explores advanced systems designed release active agents in controlled manner lung, with specific focus provided on effective pulmonary considerations overcome challenges. The outlook this pertinent field study additionally provided, highlighting potential bioactive prevention variety ailments.

Language: Английский

---

Recent Advances and Prospects in RNA Drug Development

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12284 - 12284

Published: Nov. 15, 2024

RNA therapeutics have undergone remarkable evolution since their inception in the late 1970s, revolutionizing medicine by offering new possibilities for treating previously intractable diseases. The field encompasses various modalities, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), and messenger (mRNAs), each with unique mechanisms applications. foundation was laid 1978 discovery that synthetic could inhibit viral replication, followed pivotal developments such as interference's 1998. COVID-19 pandemic marked a crucial turning point, demonstrating potential of mRNA vaccines accelerating interest RNA-based approaches. However, significant challenges remain, stability issues, delivery to target tissues, off-target effects, immunogenicity concerns. Recent advancements chemical modifications, systems, integration AI technologies are addressing these challenges. has seen notable successes, approved treatments spinal muscular atrophy hereditary transthyretin-mediated amyloidosis. Looking ahead, show promise personalized approaches, particularly genetic disorders cancer. continued this field, driven technological innovations deeper understanding biology, suggests transformative impact on future medical treatments. purpose review is provide comprehensive overview evolution, current state, prospects therapeutics.

Language: Английский

---

Nanoparticle Targeting Strategies for Lipid and Polymer‐Based Gene Delivery to Immune Cells In Vivo

Small Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 30, 2024

Lipid nanoparticles and polymeric are promising biomaterial platforms for robust intracellular DNA mRNA delivery, highlighted by the widespread use of nanoparticle‐ (NP) based vaccines to help end COVID‐19 pandemic. Recent research has sought adapt this nanotechnology transfect engineer immune cells in vivo. The system is an especially appealing target due its involvement many different diseases, ex vivo‐engineered cell therapies like chimeric antigen receptor (CAR) T therapy have already demonstrated remarkable clinical success certain blood cancers. Although gene delivery can potentially address some cost manufacturing concerns associated with current autologous therapies, transfecting vivo challenging. Not only extrahepatic NP lymphoid organs difficult, but particular resistance transfection. Despite these challenges, modular nature NPs allows researchers examine critical structure–function relationships between a particle's properties ability specifically Herein, several nanomaterial components outlined, including targeting ligands, nucleic acid cargo, chemical properties, physical route administration optimal

Language: Английский

---

Personalized mRNA vaccines in glioblastoma therapy: from rational design to clinical trials

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 4, 2024

Abstract Glioblastomas (GBMs) are the most common and aggressive malignant brain tumors, presenting significant challenges for treatment due to their invasive nature localization in critical regions. Standard includes surgical resection followed by radiation adjuvant chemotherapy with temozolomide (TMZ). Recent advances immunotherapy, including use of mRNA vaccines, offer promising alternatives. This review focuses on emerging vaccines GBM treatment. We summarize recent advancements, evaluate current obstacles, discuss notable successes this field. Our analysis highlights that while have shown potential, is still experimental. Ongoing research clinical trials essential fully understand therapeutic potential. Future developments vaccine technology insights into GBM-specific immune responses may lead more targeted effective treatments. Despite promise, further crucial validate optimize effectiveness combating GBM. Graphical

Language: Английский

---

Tailoring Nanovectors for Optimal Neoantigen Vaccine Efficacy

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The primary objective of neoantigen vaccines is to elicit a robust anti-tumor immune response by generating neoantigen-specific T cells that can eradicate tumor cells. Despite substantial advancements in personalized prediction using next-generation sequencing, machine learning, and mass spectrometry, challenges remain efficiently expanding cell populations vivo. This challenge impedes the widespread clinical application vaccines. Nanovector-based delivery systems have emerged as promising solutions this challenge. These nanovectors offer several advantages, such enhanced stability, targeted intracellular delivery, sustained release, improved antigen-presenting (APC) activation. Notably, they effectively deliver various vaccine formulations (DC cell-based, synthetic long peptide (SLP)-based or DNA/mRNA-based) APCs cells, thereby activating both CD4+ CD8+ ultimately induces specific response. review focuses on recent innovations vectors. We aim identify optimal design parameters for vectors tailored different types, with an emphasis enhancing microenvironment stimulating production cytotoxic By maximizing potential these systems, we accelerate translation nanovaccines advance cancer immunotherapy.

Language: Английский

---

Revolutionizing mRNA Vaccines Through Innovative Formulation and Delivery Strategies

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 359 - 359

Published: March 1, 2025

Modernization of existing methods for the delivery mRNA is vital in advanced therapeutics. Traditionally, has faced obstacles poor stability due to enzymatic degradation. This work examines cutting-edge formulation and emerging techniques safer vaccines. Inspired by success lipid nanoparticles (LNP) delivering vaccines COVID-19, a variety other formulations have been developed deliver diverse infections. The meritorious features nanoparticle-based strategies, including LNP, polymeric, dendrimers, polysaccharide-based, peptide-derived, carbon metal-based, DNA nanostructures, hybrid, extracellular vesicles, examined. impact these platforms on vaccine efficacy, protection from degradation, cellular uptake, controlled release, immunogenicity discussed detail. Even with significant developments, there are certain limitations overcome, toxicity concerns, limited information about immune pathways, need maintain cold chain, necessity optimizing administration methods. Continuous innovation essential improving systems Future research directions proposed address challenges expand their potential prophylactic therapeutic application.

Language: Английский

---

Engineered-affibody conjugates contribute to the specific targeting and cellular retention of polyplexes in Erbb3 overexpressed lung cancer cells

European Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 107090 - 107090

Published: March 1, 2025

Ligand-modified nanoparticles have shown the ability to specifically bind tumor cells, improving retention in tumors after initial accumulation driven by enhanced permeability and effect. These particles are typically engineered receptors overexpressed cancer cells compared healthy such as Erbb3 receptor lung cancer. In this study, we confirmed overexpression of various KRAS mutant cell lines. An affibody, well-established previous research, was selected target a proof concept. The affibody integrated into particle system via two distinct strategies. pre-functionalization approach, conjugated PEI or C14-PEI using SPDP linker. A spectral shift technique then used assess affinity conjugates toward ErbB3, allowing us estimate half-maximal effective concentration (EC50). Following synthesis characterization, polyplex formulations were prepared, including mRNA complexes with PEI-affibody, C14-PEI/PEI-affibody, C14-PEI/C14-PEI-affibody. post-functionalization composed different blends functionalized Azido-PEI initially prepared subsequently modified DBCO-functionalized click chemistry. at nitrogen phosphate (N/P) ratios characterized terms size, polydispersity index (PDI), zeta potential. We also evaluated cellular uptake eGFP expression understand how influenced ligand-modified properties delivery behavior. Our results demonstrated that can promote KRAS-mutated cells. further analyzed impact conjugation methods density on design performance. conclusion, study highlights advantages specific targeting ligands. By optimizing formulation components, methods, ligand density, ligands be attached polyplexes, enhancing cell-specific targeting, internalization, retention. findings provide valuable insights foundation for future targeted therapies design.

Language: Английский

---

Persistence and control of viruses on fomites and environmental matrices

Future Virology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: April 21, 2025

Language: Английский

---

Adrinogenic Colon Cancer Treatment Using Poly (β-Amino Esters) (PBAEs): Mechanistic Insights, Advanced Utilization Approaches, and Future Directions

Journal of Macromolecular Science Part B, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: April 27, 2025

Language: Английский

---

Tailoring Alkyl Side Chains of Ionizable Amino-Polyesters for Enhanced In Vivo mRNA Delivery

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Lipid nanoparticles (LNPs) containing ionizable lipids are the most clinically advanced platform for mRNA delivery, but their application beyond liver remains challenging. Polymer-lipid hybrid offer a promising alternative, combining synthetic versatility and unique properties of polymers with biocompatibility lipid excipients. While significance alkyl tail design is well-recognized lipids, impact polymer side chain composition on interactions excipients, delivery efficacy, tissue specificity poorly understood. Here, we focus class amino-polyesters (APEs) that exhibit features desired potential clinical applications, including narrow molecular weight distribution good safety profile, investigate effect formulation APE (APE-LNPs) delivery. A library 36 APEs was synthesized via ring-opening polymerization chemically diverse tertiary amino-alcohols lactone monomers distinct compositions, variations in length unsaturation. We show optimal critical assembly stable efficient both vitro vivo. Top-performing APE-LNPs display superior efficacy extrahepatic tissues compared to benchmark LNPs, DLin-MC3-DMA lipid. The affects selectivity APE-LNPs, shorter chains (4-5 carbons) effectively targeting spleen lungs, while longer (7-9 enhanced also explored relevance excipients demonstrating essential role unsaturated phospholipids enhancing cellular uptake limited cholesterol. These findings provide valuable insights into use LNP context, which could aid development polymeric alternatives expand utility technology nonliver tissues.

Language: Английский

---