scholarly journals Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

2020 ◽  
Vol 8 ◽  
Author(s):  
Silvia Arpicco ◽  
Michał Bartkowski ◽  
Alessandro Barge ◽  
Daniele Zonari ◽  
Loredana Serpe ◽  
...  

Hyaluronic acid (HA) is a ubiquitous biopolymer involved in many pathophysiological roles. One HA receptor, the cluster of differentiation CD44 protein, is often overexpressed in tumor cells. As such, HA has attracted considerable interest in the development of drug delivery formulations, given its intrinsic targetability toward CD44 overexpressing cells. The present study is focused on examining the correlation of HA molecular weight with its targetability properties. A library of conjugates obtained by linking the amino group of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) to the carboxylic residues of HA of different molecular weight (6.4, 17, 51, 200, and 1,500 kDa) were synthesized and fully characterized. The HA-DMPE conjugates were then used to non-covalently functionalize the highly hydrophobic single-walled carbon nanotubes (CNT), and further encapsulate the anticancer drug doxorubicin (DOX). Our results show that the complexes DOX/CNT/HA-DMPE maintain very good and stable dispersibility. Drug release studies indicated a pH-responsive release of the drug from the nanocarrier. Cell viability tests demonstrated that all HA modified CNTs have good biocompatibility, and specific targeting toward cells overexpressing the CD44 receptor. Among all the molecular weights tested, the 200 kDa HA showed the highest increase in cellular uptake and cytotoxic activity. All these promising attributes make CNT/HA200-DMPE a “smart” platform for tumor-targeted delivery of anticancer agents.

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 850 ◽  
Author(s):  
Alazne Moreno-Lanceta ◽  
Mireia Medrano-Bosch ◽  
Pedro Melgar-Lesmes

Cancer has become one of the most prevalent diseases worldwide, with increasing incidence in recent years. Current pharmacological strategies are not tissue-specific therapies, which hampers their efficacy and results in toxicity in healthy organs. Carbon-based nanomaterials have emerged as promising nanoplatforms for the development of targeted delivery systems to treat diseased cells. Single-walled carbon nanohorns (SWCNH) are graphene-based horn-shaped nanostructure aggregates with a multitude of versatile features to be considered as suitable nanosystems for targeted drug delivery. They can be easily synthetized and functionalized to acquire the desired physicochemical characteristics, and no toxicological effects have been reported in vivo followed by their administration. This review focuses on the use of SWCNH as drug delivery systems for cancer therapy. Their main applications include their capacity to act as anticancer agents, their use as drug delivery systems for chemotherapeutics, photothermal and photodynamic therapy, gene therapy, and immunosensing. The structure, synthesis, and covalent and non-covalent functionalization of these nanoparticles is also discussed. Although SWCNH are in early preclinical research yet, these nanotube-derived nanostructures demonstrate an interesting versatility pointing them out as promising forthcoming drug delivery systems to target and treat cancer cells.


Materials ◽  
2020 ◽  
Vol 13 (11) ◽  
pp. 2659 ◽  
Author(s):  
David Rebenda ◽  
Martin Vrbka ◽  
Pavel Čípek ◽  
Evgeniy Toropitsyn ◽  
David Nečas ◽  
...  

Hyaluronic acid (HA) injections represent one of the most common methods for the treatment of osteoarthritis. However, the clinical results of this method are unambiguous mainly because the mechanism of action has not been clearly clarified yet. Viscosupplementation consists, inter alia, of the improvement of synovial fluid rheological properties by injected solution. The present paper deals with the effect of HA molecular weight on the rheological properties of its solutions and also on friction in the articular cartilage model. Viscosity and viscoelastic properties of HA solutions were analyzed with a rotational rheometer in a cone–plate and plate–plate configuration. In total, four HA solutions with molecular weights between 77 kDa and 2010 kDa were tested. The frictional measurements were realized on a commercial tribometer Bruker UMT TriboLab, while the coefficient of friction (CoF) dependency on time was measured. The contact couple consisted of the articular cartilage pin and the plate made from optical glass. The contact was fully flooded with tested HA solutions. Results showed a strong dependency between HA molecular weight and its rheological properties. However, no clear dependence between HA molecular weight and CoF was revealed from the frictional measurements. This study presents new insight into the dependence between rheological and frictional behavior of the articular cartilage, while such an extensive investigation has not been presented before.


2020 ◽  
Vol 21 (23) ◽  
pp. 8932
Author(s):  
Jing Wang ◽  
Li Liu ◽  
Aoning Wang ◽  
Xiang Liu ◽  
Yi Zhang ◽  
...  

Poly(ε-caprolactone) triacrylate (PCLTA) is attractive in tissue engineering because of its good biocompatibility and processability. The crosslinking time strongly influences PCLTAs cellular behaviors. To investigate these influences, PCLTAs with different molecular weights were crosslinked under UV light for times ranging from 1 to 20 min. The crosslinking efficiency of PCLTA increased with decreasing the molecular weight and increasing crosslinking time which could increase the gel fraction and network stiffness and decrease the swelling ratio. Then, the PCLTA networks crosslinked for different time were used as substrates for culturing rat aortic smooth muscle cells (SMCs). SMC attachment and proliferation all increased when the PCLTA molecular weight increased from 8k to 10k and then to 20k at the same crosslinking time. For the same PCLTA, SMC attachment, proliferation, and focal adhesions increased with increasing the crosslinking time, in particular, between the substrates crosslinked for less than 3 min and longer than 5 min. This work will provide a good experimental basis for the application of PCLTA.


2019 ◽  
Vol 20 (16) ◽  
pp. 3894 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Alina A. Astakhova ◽  
Nadezda V. Azbukina ◽  
Sergei V. Goriainov ◽  
Viktor V. Chistyakov ◽  
...  

Hyaluronic acid (HA), a major glycosaminoglycan of the extracellular matrix, has cell signaling functions that are dependent on its molecular weight. Anti-inflammatory effects for high-molecular-weight (HMW) HA and pro-inflammatory effects for low-molecular-weight (LMW) HA effects were found for various myeloid cells, including microglia. Astrocytes are cells of ectodermal origin that play a pivotal role in brain inflammation, but the link between HA with different molecular weights and an inflammatory response in these cells is not clear. We tested the effects of LMW and HMW HA in rat primary astrocytes, stimulated with Poly:IC (PIC, TLR3 agonist) and lipopolysaccharide (LPS, TLR4 agonist). Oxylipin profiles were measured by the UPLC-MS/MS analysis and metabolites HDoHEs (from docosahexaenoic acid), -HETEs, prostaglandins (from arachidonic acid), DiHOMEs and HODEs (from linoleic acid) were detected. Both, HMW and LMW HA downregulated the cyclooxygenase-mediated polyunsaturated fatty acids metabolism, LMW also reduced lipoxygenase-mediated fatty acid metabolism. Taken together, the data show that both LMW and HMW (i) influence themselves on cytokines (TNFα, IL-6, IL-10), enzymes iNOS, COX-2, and oxylipin levels in extracellular medium of cultured astrocytes, (ii) induced cellular adaptations in long-term applications, (iii) modulate TLR4- and TLR3-signaling pathways. The effects of HMW and LMW HA are predominantly revealed in TLR4– and TLR3- mediated responses, respectively.


2016 ◽  
Vol 8 (36) ◽  
pp. 23437-23449 ◽  
Author(s):  
Sreeranjini Pulakkat ◽  
Sai A Balaji ◽  
Annapoorni Rangarajan ◽  
Ashok M. Raichur

Cosmetics ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 71
Author(s):  
Kelly Yorke ◽  
Samiul Amin

Recently, consumers have become invested in more natural and sustainable ingredients contained in personal care products. Unfortunately, cationic surfactants are still heavily relied on as primary conditioning agents in products such as conditioning shampoos because of their ability to cling well to the negatively charged surface of hair follicles. Additionally, sulfates are utilized as cleansing agents because they are highly effective and low cost. The objective of this study is to find a more sustainable formulation for a conditioning shampoo without compromising the desired wet combing, rheological, and surface activity properties. The systems which were investigated contained hyaluronic acid (HA) at a variety of molecular weights and concentrations, in combination with a surfactant, either acidic sophorolipid (ASL) or alkyl polyglucoside (APG), and varying the presence of sodium chloride. A Dia-stron was utilized to test the wet combing force, a rheometer recorded the viscosity at various shear rates, and a tensiometer measured the surface tension of the samples before a visual foaming study was conducted. Molecular weight and concentration seemed to have a large impact on wet combing force, as well as rheology, with the largest molecular weight and concentration producing the lowest friction coefficient and desired rheological profile. The addition of a surfactant significantly aids in the reduction in surface tension and increased foamability. Therefore, the optimal system to achieve the largest reduction in wet combing force, large viscosity with shear-thinning behavior, and relatively low surface tension with decent foaming is composed of 1% HA at 800 kDa, 10% ASL and 1% NaCl. This system shows a viable sulfate-free and silicone-free option that can achieve both conditioning and cleansing.


2021 ◽  
Author(s):  
Bo Mi Lee ◽  
Sang Jun Park ◽  
Insup Noh ◽  
Chun-Ho Kim

Abstract Background: The molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages. Methods: The structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by 1H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (100 μg/mL) or high (100 μg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR.Results: Molecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241±161, 96,531±1,167, 512,657±8,545, and 1,249,500±37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 μg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45%. Using NanoString technology, we also found that the immune-related genes TNF‐α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 μg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages.Conclusions: High molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.


Author(s):  
Tanima Bhattacharya ◽  
Samka Peregrine Maishu ◽  
Rokeya Akter ◽  
Md. Habibur Rahman ◽  
Muhammad Furqan Akhtar ◽  
...  

: Cancer notably carcinoma represents a prominent health challenge worldwide. A variety of chemotherapeutic agents are being used to deal with a variety of carcinomas. However, these delivering agents not only enter the targeted site but also affect normal tissues yielding poor therapeutic outcomes. Chemotherapeutic-associated problems are been attributed to drug non-specificity resulting from poor drug delivery systems. These problems are now been solved using nanomedicine which entails using nanoparticles as drug delivery systems or nanocarriers. This nanoparticle-based drug delivery system enhances clinical outcomes by enabling targeted delivery, improving drug internalization, enhanced permeability, easy biodistribution, prolonged circulation and enhanced permeability rate thereby improving therapeutic effectiveness of several anticancer agents. Natural protein-based nanoparticles (PNPs) such as ferritin, lipoprotein, and lectins from natural sources have gained extensive importance at scientific community level as nanovehicle for effective drug delivery and photo acoustic labeling replacing several synthetic nanocarriers that have shown limited therapeutic outcomes. The bioavailability of PNP, chance of genetic engineering techniques to modify their biological properties made them one of the important raw material sources for drug delivery research. This current review highlighted different chemotherapeutic agents used in the treatment of some carcinomas. It also focused on the wide variety of natural protein sources derived nanoparticles (NPs) as anticancer delivery of agents for cancer therapy.


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