Functionalized Particles Designed for Targeted Delivery

Basiǹska, Teresa; Gadzinowski, Mariusz; Mickiewicz, Damian; Słomkowski, Stanisław

doi:10.3390/polym13122022

Cited by 14 publications

(8 citation statements)

References 247 publications

(511 reference statements)

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“…Compared to unmodified starch, dextrins have improved water solubility and form solutions with lower viscosity [55]. Maltodextrin (MD) is produced by acidic and/or controlled enzymatic hydrolysis of starch and it is composed of D-glucose blocks bound by α-(1,4) and α- (1,6) bonds. It contains 2-3% glucose and 5-7% maltose.…”

Section: Preparation Of Maltodextrin Microparticlesmentioning

confidence: 99%

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Application of Starch, Cellulose, and Their Derivatives in the Development of Microparticle Drug-Delivery Systems

Lukova,

Katsarov,

Pilicheva

2023

Polymers

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Micro- and nanotechnologies have been intensively studied in recent years as novel platforms for targeting and controlling the delivery of various pharmaceutical substances. Microparticulate drug delivery systems for oral, parenteral, or topical administration are multiple unit formulations, considered as powerful therapeutic tools for the treatment of various diseases, providing sustained drug release, enhanced drug stability, and precise dosing and directing the active substance to specific sites in the organism. The properties of these pharmaceutical formulations are highly dependent on the characteristics of the polymers used as drug carriers for their preparation. Starch and cellulose are among the most preferred biomaterials for biomedical applications due to their biocompatibility, biodegradability, and lack of toxicity. These polysaccharides and their derivatives, like dextrins (maltodextrin, cyclodextrins), ethylcellulose, methylcellulose, hydroxypropyl methylcellulose, carboxy methylcellulose, etc., have been widely used in pharmaceutical technology as excipients for the preparation of solid, semi-solid, and liquid dosage forms. Due to their accessibility and relatively easy particle-forming properties, starch and cellulose are promising materials for designing drug-loaded microparticles for various therapeutic applications. This study aims to summarize some of the basic characteristics of starch and cellulose derivatives related to their potential utilization as microparticulate drug carriers in the pharmaceutical field.

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Section: Preparation Of Maltodextrin Microparticlesmentioning

confidence: 99%

“…Controlled-release polymer microparticles can also increase drug stability, especially in molecules that are prone to rapid degradation in the body. Such formulations are generally associated with a significant reduction in the number of applications and better patient acceptance [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Application of Starch, Cellulose, and Their Derivatives in the Development of Microparticle Drug-Delivery Systems

Lukova,

Katsarov,

Pilicheva

2023

Polymers

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“…Polymeric nanoparticles have been proposed as one promising modality for brain drug delivery due to their advantages, including enhanced solubility of drug payload, reduced drug metabolism, biodegradability, enhanced therapeutic efficacy, and reduced toxicity relative to the administration of free drugs. , Additionally, polymeric nanoparticles can be easily engineered by tuning their physicochemical properties based on the targeted application with enhanced delivery to brain. − Nevertheless, these studies are still far from optimal as the accumulation in the liver reduces the overall availability of the drug in the CNS. , One of the common ways to enhance drug delivery across the BBB is to adorn the surface of these bespoke nanomaterials with targeting ligands that can be recognized by the receptors expressed on the BBB and internalized via the process of endocytosis. ,− In addition to the nanoparticle size, shape, surface charge, − ligand type, conjugation strategy, orientation, and ligand density have recently emerged as critical parameters that significantly dictate the mechanism and kinetics of its cellular interaction. , In a recent review article, it was demonstrated that when the ligand density increases, the cellular association increases to a limit, after which a constant or decreased association is observed . Interestingly, targeted nanoparticles often qualitatively report the ligand density as ‘low’, ‘intermediate’, and ‘high’, or as a percentage and only a few reports quantitatively determine the number of ligands per nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Folic Acid-Conjugated Brush Polymers Show Enhanced Blood–Brain Barrier Crossing in Static and Dynamic In Vitro Models Toward Brain Cancer Targeting Therapy

Mazrad,

Refaat,

Morrow

et al. 2024

ACS Biomater. Sci. Eng.

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Over the past decades, evidence has consistently shown that treatment of central nervous system (CNS)-related disorders, including Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, and brain cancer, is limited due to the presence of the blood−brain barrier (BBB). To assist with the development of new therapeutics, it is crucial to engineer a drug delivery system that can cross the BBB efficiently and reach target cells within the brain. In this study, we present a potentially efficient strategy for targeted brain delivery through utilization of folic acid (FA)-conjugated brush polymers, that specifically target the reduced folate carrier (RFC, SLC19A1) expressed on brain endothelial cells. Here, azide (N 3 )-decorated brush polymers were prepared in a straightforward manner coupling a heterotelechelic α-NH 2 , ω-N 3 -poly(2-ethyl-2oxazoline) (NH 2 -PEtOx-N 3 ) to N-acylated poly(amino ester) (NPAE)-based brushes. Strain-promoted azide−alkyne cycloaddition (SPAAC) 'click chemistry' with DBCO-folic acid (FA) yielded FA-brush polymers. Interestingly, while azide functionalization of the brush polymers dramatically reduced their association to brain microvascular endothelial cells (hCMEC/D3), the introduction of FA to azide led to a substantial accumulation of the brush polymers in hCMEC/D3 cells. The ability of the polymeric brush polymers to traverse the BBB was quantitatively assessed using different in vitro BBB models including static Transwell and microfluidic platforms. FA-brush polymers showed efficient transport across hCMEC/D3 cells in a manner dependent on FA composition, whereas nonfunctionalized brush polymers exhibited limited trafficking under the same conditions. Further, cellular uptake inhibition studies suggested that the interaction and transport pathway of FA-brush polymers across BBB relies on the RFC-mediated pathways. The potential application of the developed FA-brush polymers in brain cancer delivery was also investigated in a microfluidic model of BBB-glioblastoma. Brush polymers with more FA units successfully presented an enhanced accumulation into U-87 MG glioma cells following its BBB crossing, compared to controls. These results demonstrate that FA-modified brush polymers hold a great potential for more efficient delivery of future brain therapeutics.

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“…Among abiotic vector systems there are polymer [10], lipid [11,12], magnetic [13], and gold-based nanoparticles [12]. Such delivery systems have a number of distinct advantages, in particular, an ability to load large-sized components, ease of formation, low toxicity, minimal immune response [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Biomineralization of Human Genomic DNA into ZIF-8, a Zeolite-Like Metal-Organic Framework

Shaykhutdinov,

Iliasov,

Limareva

et al. 2024

Sovrem Tehnol Med

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The aim of the study was to assess the capabilities of human genomic DNA biomineralization into ZIF-8 metal-organic framework (MOF) preserving DNA sequence integrity after the encapsulation cycle and composite dissolving. The study is an initial stage of the project aimed at developing an abiotic vector to be used when working with native nucleic acids of an arbitrary size based on DNA@ZIF-8 composite.Materials and Methods. We studied human genomic DNA isolated from lymphocytes of peripheral blood of healthy volunteers using Proba-NK kit (DNA-Technology LLC, Russia). Genomic DNA purity and concentration was estimated spectrophotometrically at 260/280 nm using Tecan Infinity 200 Pro plate reader (Tecan Instruments, Austria). ZIF-8 was synthesized in the physiological conditions (37°C) by mixing zinc salt and 2-methylimidazole aqueous solutions at different molar ratios. Human genomic DNA was encapsulated into ZIF-8 in similar conditions. The obtained MOF and DNA@ZIF-8 composite were studied using X-ray powder diffraction at the Phaser D2 XRPD device (Bruker, USA), and the specific surface area was estimated using Autosorb iQ porosimetry analyzer (Quantachrome, USA). The encapsulated DNA was quantified by dissolving DNA@ZIF-8 composite in the citrate buffer. DNA integrity was assessed by real-time allele-specific PCR (AS-PCR) using the kits for single nucleotide polymorphisms (Lytech, Russia) at the Quantstudio 6 Pro PCR machine (Thermo Scientific, USA). In case of using the kits with electrophoretic detection, the amplification was performed on the thermal cycler T100 (Thermo Scientific, USA).Results. The polymer ZIF-8 and DNA@ZIF-8 composite were obtained at different molar ratios of zinc ions and 2-methylimidazole. We characterized their structure and specific surface area. Genomic DNA biomineralization efficacy was found to be about 7-8%. PCR indicated the integrity of non-selectively chosen loci within the biomineralized DNA.Conclusion. The study confirmed the possibility of human genomic DNA encapsulation into ZIF-8 metal-organic framework. After the biomineralization, DNA was found to preserve feasibility to be used in studies to investigate genetic constructs.

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Functionalized Particles Designed for Targeted Delivery

Cited by 14 publications

References 247 publications

Application of Starch, Cellulose, and Their Derivatives in the Development of Microparticle Drug-Delivery Systems

Application of Starch, Cellulose, and Their Derivatives in the Development of Microparticle Drug-Delivery Systems

Folic Acid-Conjugated Brush Polymers Show Enhanced Blood–Brain Barrier Crossing in Static and Dynamic In Vitro Models Toward Brain Cancer Targeting Therapy

Biomineralization of Human Genomic DNA into ZIF-8, a Zeolite-Like Metal-Organic Framework

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