Core-Shell Bottlebrush Polymers: Unmatched Delivery of Small Active Compounds Deep Into Tissues.

The chemical structure of a delivery nanovehicle plays a pivotal role in determining the efficiency of drug delivery within the body. Leveraging the unique architecture of bottlebrush (BB) polymers-characterized by variations in backbone length, grafting density, and self-assembly morphology-offers a novel approach to understanding the influence of structural properties on biological behavior. In this study, developed a drug delivery system based on core-shell BB polymers synthesized using a "grafting-from" strategy.

Bioinspired Bottlebrush Polymers Effectively Alleviate Frictional Damage Both In Vitro and In Vivo.

Bottlebrush polymers (BB) have emerged as compelling candidates for biosystems to face tribological challenges, including friction and wear. This study provides a comprehensive assessment of an engineered triblock BB polymer's affinity, cell toxicity, lubrication, and wear protection in both in vitro and in vivo settings, focusing on applications for conditions like osteoarthritis and dry eye syndrome. Results show that the designed polymer rapidly adheres to various surfaces (e.

Multicompartment Micro- and Nanoparticles Using Supramolecular Assembly of Core-Shell Bottlebrush Polymers.

Multicompartment particles have been produced to date by the self-assembly of linear multiblock polymers. Besides the large diversity of structures that can be obtained with this approach, these are highly sensitive to dilution and environmental factors. Here we show that using core-shell bottlebrush polymers with a hydrophobic polyester core as starting materials it is possible to create compartmentalized particles from the micrometer size down to the molecular scale.

Deep Tissue Penetration of Bottle-Brush Polymers via Cell Capture Evasion and Fast Diffusion.

Drug nanocarriers (NCs) capable of crossing the vascular endothelium and deeply penetrating into dense tissues of the CNS could potentially transform the management of neurological diseases. In the present study, we investigated the interaction of bottle-brush (BB) polymers with different biological barriers and and compared it to nanospheres of similar composition. internalization and permeability assays revealed that BB polymers are not internalized by brain-associated cell lines and translocate much faster across a blood-brain barrier model compared to nanospheres of similar hydrodynamic diameter.

In Situ Characterization of the Protein Corona of Nanoparticles In Vitro and In Vivo.

A new theoretical framework that enables the use of differential dynamic microscopy (DDM) in fluorescence imaging mode to quantify in situ protein adsorption onto nanoparticles (NP) while simultaneously monitoring for NP aggregation is proposed. This methodology is used to elucidate the thermodynamic and kinetic properties of the protein corona (PC) in vitro and in vivo. The results show that protein adsorption triggers particle aggregation over a wide concentration range and that the formed aggregate structures can be quantified using the proposed methodology.

Therapeutic nanotechnologies for Alzheimer's disease: A critical analysis of recent trends and findings.

Alzheimer's Disease (AD) is an irreversible neurodegenerative disease for which no modifying therapies are presently available. Besides the identification of pathological targets, AD presents numerous clinical and pharmacological challenges such as efficient active delivery to the central nervous system, cell targeting, and long-term dosing. Nanoparticles have been explored to overcome some of these challenges as drug delivery vehicles or drugs themselves.

Tailoring PEGylated nanoparticle surface modulates inflammatory response in vascular endothelial cells.

Polymer nanoparticles (NPs) are extensively studied as drug delivery systems for various therapeutic indications, including drug and imaging agent delivery to the brain. Despite intensive research, their toxicological profile has yet to be fully characterized. In particular, the more subtle effects of nanomaterials on inflammatory processes have scarcely been investigated.

Nanoparticle shell structural cues drive in vitro transport properties, tissue distribution and brain accessibility in zebrafish.

Zwitterion polymers with strong antifouling properties have been suggested as the prime alternative to polyethylene glycol (PEG) for drug nanocarriers surface coating. It is believed that PEG coating shortcomings, such as immune responses and incomplete protein repellency, could be overcome by zwitterionic polymers. However, no systematic study has been conducted so far to complete a comparative appraisal of PEG and zwitterionic-coating effects on nanoparticles (NPs) stealthness, cell uptake, cell barrier translocation and biodistribution in the context of nanocarriers brain targeting.

Glutathione: An Old and Small Molecule with Great Functions and New Applications in the Brain and in Alzheimer's Disease.

Glutathione (GSH) represents the most abundant and the main antioxidant in the body with important functions in the brain related to Alzheimer's disease (AD). Oxidative stress is one of the central mechanisms in AD. We and others have demonstrated the alteration of GSH levels in the AD brain, its important role in the detoxification of advanced glycation end-products and of acrolein, a by-product of lipid peroxidation.

Transport of PEGylated-PLA nanoparticles across a blood brain barrier model, entry into neuronal cells and in vivo brain bioavailability.

Treatments of neurodegenerative diseases (NDDs) are severely hampered by the presence of the blood-brain barrier (BBB) precluding efficient brain drug delivery. The development of drug nanocarriers aims at increasing the brain therapeutic index would represent a real progress in brain disease management. PEGylated polyester nanoparticles (NPs) are intensively tested in clinical trials for improved drug delivery.

Overcoming the Brain Barriers: From Immune Cells to Nanoparticles.

Nanoparticulate carriers, often referred to as nanoparticles (NPs), represent an important pharmacological advance for drug protection and tissue-specific drug delivery. Accessing the central nervous system (CNS), however, is a complex process regulated by mainly three brain barriers. While some leukocyte (i.

Spontaneous shrinking of soft nanoparticles boosts their diffusion in confined media.

Improving nanoparticles (NPs) transport across biological barriers is a significant challenge that could be addressed through understanding NPs diffusion in dense and confined media. Here, we report the ability of soft NPs to shrink in confined environments, therefore boosting their diffusion compared to hard, non-deformable particles. We demonstrate this behavior by embedding microgel NPs in agarose gels.

Subtle and unexpected role of PEG in tuning the penetration mechanisms of PLA-based nano-formulations into intact and impaired skin.

We present a systematic study of the role of poly(ethylene glycol) (PEG) content in NPs on drug skin absorption. Cholecalciferol-loaded NPs of 100 nm of diameter were prepared by flash nanoprecipitation from PLA-b-PEG copolymers of various PEG lengths. As PEG content increased in the polymer, we observed a transition from a frozen solid particle structure to a more dynamic particle structure.

Nanoparticle heterogeneity: an emerging structural parameter influencing particle fate in biological media?

Drug nanocarriers' surface chemistry is often presumed to be uniform. For instance, the polymer surface coverage and distribution of ligands on nanoparticles are described with averaged values obtained from quantification techniques based on particle populations. However, these averaged values may conceal heterogeneities at different levels, either because of the presence of particle sub-populations or because of surface inhomogeneities, such as patchy surfaces on individual particles.

Effect of surface chemistry of polymeric nanoparticles on cutaneous penetration of cholecalciferol.

We investigated the influence of nanoparticle (NP) surface composition on different aspects of skin delivery of a lipophilic drug: chemical stability, release and skin penetration. Cholecalciferol was chosen as a labile model drug. Poly(lactic acid) (PLA)-based NPs without surface coating, with a non-ionic poly(ethylene glycol) (PEG) coating, or with a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) coating were prepared using flash nanoprecipitation.

Unified Scaling of the Structure and Loading of Nanoparticles Formed by Diffusion-Limited Coalescence.

The present study establishes the scaling laws describing the structure of spherical nanoparticles formed by diffusion-limited coalescence. We produced drug-loaded nanoparticles from a poly(ethylene glycol)-poly(d,l-lactic acid) diblock polymer (PEG- b-PLA) by the nanoprecipitation method using different types of micromixing chambers to explore multiple mixing regimes and characteristic times. We first show that the drug loading of the nanoparticles is not controlled by the mixing time but solely by the drug-to-polymer ratio (D:P) in the feed and the hydrophobicity of the drug scaled via the partition coefficient P.

Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS.

We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure.

Effect of the Polymer Architecture on the Structural and Biophysical Properties of PEG-PLA Nanoparticles.

Polymers made of poly(ethylene glycol) chains grafted to poly(lactic acid) chains (PEG-g-PLA) were used to produce stealth drug nanocarriers. A library of comblike PEG-g-PLA polymers with different PEG grafting densities was prepared in order to obtain nanocarriers with dense PEG brushes at their surface, stability in suspension, and resistance to protein adsorption. The structural properties of nanoparticles (NPs) produced from these polymers by a surfactant-free method were assessed by dynamic light scattering, ζ potential, and transmission electron microscopy and found to be controlled by the amount of PEG present in the polymers.

Assessment of PEG on polymeric particles surface, a key step in drug carrier translation.

Injectable drug nanocarriers have greatly benefited in their clinical development from the addition of a superficial hydrophilic corona to improve their cargo pharmacokinetics. The most studied and used polymer for this purpose is poly(ethylene glycol), PEG. However, in spite of its wide use for over two decades now, there is no general consensus on the optimum PEG chain coverage-density and size required to escape from the mononuclear phagocyte system and to extend the circulation time.

Characterization of rhodamine loaded PEG-g-PLA nanoparticles (NPs): effect of poly(ethylene glycol) grafting density.

In our previous study, PEG-g-PLA nanoparticles were developed and characterized. The aim of the present work is to investigate the effect of PEG grafting density (% PEG inserted onto poly(d, l)-lactide, PLA backbone) on both physicochemical and biological properties (mainly plasma protein binding and in vitro macrophage uptake) of PEG-g-PLA NPs. Rhodamine B (RHO) loaded NPs were prepared from a 1:1 (wt/wt) blend of PLA and PEG-g-PLA copolymer of varying PEG grafting density (1, 7, or 20% mol/mol of lactic acid monomer) by an o/w emulsion solvent evaporation method.

Effect of polyethylene glycol (PEG) chain organization on the physicochemical properties of poly(D, L-lactide) (PLA) based nanoparticles.

The aim of the present study is to evaluate the effect of polyethylene glycol (PEG) chain organization on various physicochemical aspects of drug delivery from poly(D, L-lactide) (PLA) based nanoparticles (NPs). To reach that goal, two different pegylated polymers of poly(D, L-lactide) (PLA) were synthesized. Polymers used in this study are grafted ones in which PEG was grafted on PLA backbone at 7% (mol/mol of lactic acid monomer), PEG7%-g-PLA, and multiblock copolymer of both PLA and PEG, (PLA-PEG-PLA)n with nearly similar PEG insertion ratio and the same PEG chain length.

Effect of aqueous solubility of grafted moiety on the physicochemical properties of poly(d,l-lactide) (PLA) based nanoparticles.

In order to evaluate the solubility effect of grafted moiety on the physicochemical properties of poly(d,l-lactide) (PLA) based nanoparticles (NPs), two materials of completely different aqueous solubility, polyethylene glycol (PEG) and palmitic acid were grafted on PLA backbone at nearly the same grafting density, 2.5% (mol of grafted moiety/mol of lactic acid monomer). Blank and ibuprofen-loaded NPs were fabricated from both polymers and their properties were compared to PLA homopolymer NPs as a control.

Progress technology in microencapsulation methods for cell therapy.

Cell encapsulation in microcapsules allows the in situ delivery of secreted proteins to treat different pathological conditions. Spherical microcapsules offer optimal surface-to-volume ratio for protein and nutrient diffusion, and thus, cell viability. This technology permits cell survival along with protein secretion activity upon appropriate host stimuli without the deleterious effects of immunosuppressant drugs.