scholarly journals Redox/pH-Responsive Biodegradable Thiol-Hyaluronic Acid/Chitosan Charge-Reversal Nanocarriers for Triggered Drug Release

Polymers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 3785
Author(s):  
Dandan Xia ◽  
Feilong Wang ◽  
Shuo Pan ◽  
Shenpo Yuan ◽  
Yunsong Liu ◽  
...  

Biodegradable nanoparticles and micelles are promising nanosystems for the targeted delivery of potent anticancer drugs. By using specialized polymers as nanocarriers, targeted drug delivery and release can be developed. We developed thiol-hyaluronic acid (HA-SH)/chitosan (CS) nanoparticles with redox/pH dual-responsiveness via electrostatic self-assembly followed by spontaneous chemical cross-linking. The nanoparticle surface charges were reversible through different HA-SH and CS mass ratios. Doxorubicin (DOX) was used as a model drug. Dual cross-linked nanoparticles with diameters of approximately 300 nm exhibited superior stability under physiological conditions compared with nanoparticles without disulfide cross-linking. DOX was loaded more efficiently into negative nanoparticles (45.7 wt%) than positive nanoparticles (14.2 wt%). Drug release from negative nanoparticles (ζ potential of approximately −20) was higher (87.8 wt%) at pH 4.5 and in the presence of 10 mM glutathione. Positive nanoparticles (ζ potential of approximately +20) showed the same trend, but the release rate was slower than that of negative nanoparticles. DOX-loaded HA-SH/CS particles were taken up by human breast cancer cells (SKBR3), and the loaded drug was released, exhibiting potential antitumor efficacy. The HA-SH/CS nanoparticles in this study were stable under physiological conditions and are promising candidates for the targeted delivery and release of anticancer drugs.

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 261 ◽  
Author(s):  
Minmin Chang ◽  
Xinxin Liu ◽  
Ling Meng ◽  
Xiaohui Wang ◽  
Junli Ren

Pore-forming agents have a significant influence on the pore structure of hydrogels. In this study, a porogenic technique was employed to investigate the preparation of macroporous hydrogels which were synthesized by radical copolymerization of carboxymethyl xylan with acrylamide and N-isopropylacrylamide under the function of a cross-linking agent. Six kinds of pore-forming agents were used: polyvinylpyrrolidone K30, polyethylene glycol 2000, carbamide, NaCl, CaCO3, and NaHCO3. The application of these hydrogels is also discussed. The results show that pore-forming agents had an important impact on the pore structure of the hydrogels and consequently affected properties of the hydrogels such as swelling ratio and mechanical strength, while little effect was noted on the thermal property of the hydrogels. 5-Fluorouracil was used as a model drug to study the drug release of the as-prepared hydrogels, and it was found that the drug release was substantially improved after using the NaHCO3 pore-forming agent: a cumulative release rate of up to 71.05% was achieved.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yu Gao ◽  
Lili Hu ◽  
Ying Liu ◽  
Xiaoyan Xu ◽  
Chao Wu

Hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (HMHA) were used as a tumor-targeted delivery carrier for liver cancer therapy. Paclitaxel (PAC) incorporated in the carrier by the adsorption method was analyzed by X-ray diffraction and differential scanning calorimetry. PAC was found to be in an amorphous state. The hyaluronic acid coated on the surface of mesoporous hollow alumina nanoparticles (MHA) regulated the drug release rate and the loaded samples obtained a sustained drug release. In vitro experiments demonstrated that paclitaxel-hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (PAC-HMHA) had a high cellular uptake, which increased the drug level in tumor tissues and was beneficial to promote apoptosis. An in vivo tumor inhibition rate study demonstrated that PAC-HMHA (64.633 ± 4.389%) had a better antitumor effect than that of paclitaxel-mesoporous alumina nanoparticles (PAC-MHA, 56.019 ± 6.207%) and pure PAC (25.593 ± 4.115%). Therefore it can be concluded that PAC-HMHA are a prospective tumor-targeted delivery medium and can be useful for future cancer therapy.


Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1181 ◽  
Author(s):  
Somayeh Rezaei ◽  
Soheila Kashanian ◽  
Yadollah Bahrami ◽  
Luis J. Cruz ◽  
Marjan Motiei

Novel reduction-responsive hyaluronic acid–chitosan–lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast cancer by targeting Cluster of Differentiation 44 (CD44)-overexpressing cells and reduction-triggered 17α-Methyltestosterone (MT) release for systemic delivery. The effectiveness of these nanoparticles was investigated by different assays, including release rate, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), lactate dehydrogenase (LDH), caspase-3 activity, Rhodamine 123 (RH-123), and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). In vitro experiments revealed that Methyltestosterone/Hyaluronic acid–chitosan–lipoic acid nanoparticles (MT/HACSLA-NPs) illustrated a sustained drug release in the absence of glutathione (GSH), while the presence of GSH led to fast MT release. HACSLA-NPs also showed high cellular internalization via CD44 receptors, quick drug release inside the cells, and amended cytotoxicity against positive CD44 BT-20 breast cancer cell line as opposed to negative CD44, Michigan Cancer Foundation-7 (MCF-7) cell line. These findings supported that these novel reduction-responsive NPs can be promising candidates for efficient targeted delivery of therapeutics in cancer therapy.


2021 ◽  
Author(s):  
Maja Markovic ◽  
◽  
Vesna Panic ◽  
Julijana Tadic ◽  
Rada Pjanovic

Targeted drug delivery is powerful tool which researchers use to achieve safer and more efficient therapy of many diseases, including various types of cancer. Many chemotherapeutics are poorly water- soluble, so their encapsulation and targeted delivery remain quite challenge. Hydrogels based on poly(methacrylic acid) (PMAA) are widely investigated for targeted drug delivery due to their pH sensitivity, non-toxicity and biocompatibility. Still, due to the PMAA highly hydrophilic nature, PMAA can only be used for encapsulation and targeted delivery of water-soluble drugs. Our previous research was directed towards overcoming this limitation: PMAA was modified with amphiphilic protein – casein and poorly-water soluble model drug – caffeine – was encapsulated (PMAC). Present study is focused on investigation how variation of amount of one of the most important hydrogels network parameter such as crosslinker affect PMAC swelling properties and caffeine release. The group of hybrid hydrogels – PMAC – was synthesized with various amount of crosslinker: 0.4mol%, 0.8mol%, 1.6mol% and 3.2mol% with respect to methacrylic acid. Swelling behavior of hybrid hydrogels and caffeine release was investigated in two environments which simulated human stomach and intestines. Obtained results showed that targeted delivery of poorly water-soluble model drug was achieved and that its release can be prolonged up to 24h. Also, kinetic of poorly water-soluble drug release can be easily modified only by changing crosslinker amount. PMAC hybrid hydrogels have huge potential for targeted delivery of poorly water-soluble active substances.


2020 ◽  
Vol 2 ◽  
Author(s):  
Xiaoxue Hu ◽  
Ziqi Xu ◽  
Qianhao Min ◽  
Chao Teng ◽  
Ye Tian

Nanostructures specifically responsive to endogenous biomolecules hold great potential in accurate diagnosis and precision therapy of cancers. In the pool of nanostructures with responsiveness to unique triggers, nanomaterials derived from DNA self-assembly have drawn particular attention due to their intrinsic biocompatibility and structural programmability, enabling the selective bioimaging, and site-specific drug delivery in cancer cells and tumor tissues. In this mini review, we summarize the most recent advances in the development of endogenous stimuli-responsive DNA nanostructures featured with precise self-assembly, targeted delivery, and controlled drug release for cancer theranostics. This mini review briefly discusses the diverse dynamic DNA nanostructures aiming at bioimaging and biomedicine, including DNA self-assembling materials, DNA origami structures, DNA hydrogels, etc. We then elaborate the working principles of DNA nanostructures activated by biomarkers (e.g., miRNA, mRNA, and proteins) in tumor cells and microenvironments of tumor tissue (e.g., pH, ATP, and redox gradient). Subsequently, applications of the endogenous stimuli-responsive DNA nanostructures in biological imaging probes for detecting cancer hallmarks as well as intelligent carriers for drug release in vivo are discussed. In the end, we highlight the current challenges of DNA nanotechnology and the further development of this promising research direction.


2013 ◽  
Vol 23 (03n04) ◽  
pp. 135-145 ◽  
Author(s):  
S. Harada ◽  
S. Ehara ◽  
K. Ishii ◽  
T. Sato ◽  
M. Kouka ◽  
...  

We have been developing microcapsules that release anticancer drugs in response to radiation with an aim of targeted delivery and increasing the efficacy of anticancer drugs by a combination of these drugs with radiation. The aim of this study was to micronize microcapsules by adding carbonated water to the core material of microcapsules, which releases the anticancer drugs in response to radiation. The core material of microcapsules was prepared by mixing 0.1 g of hyaluronic acid and 0.2 g of alginate into 5 mL of carbonated water. The mixture was sprayed onto a 0.3 mmoL/L solution of calcium chloride (CaCl2) and ferrous chloride (FeCl2) using an ultrasound disintegrator. The vibration of the ultrasound disintegrator generated microbubbles in the carbonated water, which micronized the microcapsules. Intravenous injection of the micronized microcapsules to tumor-bearing mice showed that the micronized microcapsules passed more efficiently through the capillaries of lungs or kidneys, which resulted in increased delivery of microcapsules to the tumors and increased the anticancer effect.


2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Sharma Pankaj ◽  
Tailang Mukul

The aim of present work was to prepare colon specific delivery system of Ornidazole using different ratio of shellac, zein and guar gum. From study of various literature it revealed that shellac, zein and guar gum released drug from dosage form at the pH of 6.9, 11.5, 7-9 respectively. The main problem associated with colon targeted drug delivery system is degradation of drug in the acidic environment of stomach to circumvent the present problem different combinations of shellac, zein and guar gum were employed in the formulation of colon targeted tablet. Several preformulation parameters were determined such as melting point, FTIR spectroscopy, preparation of calibration curve, determination of λmax and partition coefficient. After the preformulation studies, next steps were preparation of core tablets, evaluation of core of tablets and coating of tablets. The data obtained from preformulation study seven formulations were developed and evaluated for various parameters. Based on evaluated parameter such as weight variation, friability, dissolution study, invitro drug release etc. the F7 formulation show better results colon targeted tablets. Drug content in F7 formulation was 95% and drug release after 6 hrs was 96%. Formulation containing combination of shellac, zein and guar gum released least amount of drug in the acidic environment of stomach and released most of the drug in colon. It is evide


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