Estrone-modified pH-sensitive glycol chitosan nanoparticles for drug delivery in breast cancer

Background: The efficacy of chemotherapy is undermined by adverse side effects and chemoresistance of target tissues. Developing a drug delivery system can reduce off-target side effects and increase the efficacy of drugs by increasing their accumulation in target tissues. Inorganic salts have several advantages over other drug delivery vectors in that they are non-carcinogenic and less immunogenic than viral vectors and have a higher loading capacity and better controlled release than lipid and polymer vectors. Methods: MgF2 crystals were fabricated by mixing 20 mM MgCl2 and 10 mM NaF and incubating for 30 min at 37 °C. The crystals were characterized by absorbance, dynamic light scattering, microscopic observance, pH sensitivity test, SEM, EDX and FTIR. The binding efficacy to doxorubicin was assessed by measuring fluorescence intensity. pH-dependent doxorubicin release profile was used to assess the controlled release capability of the particle-drug complex. Cellular uptake was assessed by fluorescence microscopy. Cytotoxicity of the particles and the drug-particle complex were assessed using MTT assay to measure cell viability of MCF-7 cells. Results and Discussion: Particle size on average was estimated to be <200 nm. The crystals were cubic in shape. The particles were pH-sensitive and capable of releasing doxorubicin in increasing acidic conditions. MgF2 nanocrystals were safe in lower concentrations, and when bound to doxorubicin, enhanced its uptake. The protein corona formed around MgF2 nanoparticles lacks typical opsonins but contains some dysopsonins. Conclusion: A drug delivery vector in the form of MgF2 nanocrystals has been developed to transport doxorubicin into breast cancer cells. It is pH-sensitive (allowing for controlled release), size-modifiable, simple and cheap to produce.

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A pH-sensitive nanocarrier based on BSA-stabilized graphene-chitosan nanocomposite for sustained and prolonged release of anticancer agents

Scientific Reports ◽

10.1038/s41598-021-97081-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sahar Gooneh-Farahani ◽

Seyed Morteza Naghib ◽

M. Reza Naimi-Jamal ◽

Amir Seyfoori

Keyword(s):

Drug Delivery ◽

Cancer Cell ◽

Electrostatic Interactions ◽

Chitosan Nanoparticles ◽

Physicochemical Characterization ◽

Ph Sensitive ◽

Release Mechanism ◽

Burst Release ◽

Prolonged Release ◽

Acidic Ph

AbstractSmart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications. Regarding their specific conditions, such as acidic pH, drug carriers to treatment of tumor microenvironment need some criteria to enhance drug delivery efficiency. In this study, for the first time, pH-sensitive BSA-stabilized graphene (BSG)/chitosan nanocomposites were synthesized through electrostatic interactions between the positively charged chitosan nanoparticles and negatively charged BSG and used for Doxorubicin (DOX) encapsulation as a general anticancer drug. Physicochemical characterization of the nanocomposites with different concentrations of BSG (0.5, 2, and 5wt%) showed effective decoration of chitosan nanoparticles on BSG. Comparing DOX release behavior from the nanocomposites and free BSG-chitosan nanoparticles were evaluated at two pHs of 7.4 and 4.5 in 28 days. It was shown that the presence of BSG significantly reduced the burst release observed in chitosan nanoparticles. The nanocomposite of 2wt% BSG was selected as the optimal nanocomposite with a release of 84% in 28 days and with the most uniform release in 24 h. Furthermore, the fitting of release data with four models including zero-order, first-order, Higuchi, and Korsmeyer-Peppas indicated that the addition of BSG changed the release mechanism of the drug, enabling uniform release for the optimal nanocomposite in first 24 h, compared to that for pure chitosan nanoparticles. This behavior was proved using metabolic activity assay of the SKBR-3 breast cancer cell spheroids exposed to DOX release supernatant at different time intervals. It was also demonstrated that DOX released from the nanocomposite had a significant effect on the suppression of cancer cell proliferation at acidic pH.

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In Silico Molecular Interaction Studies of Chitosan Polymer with Aromatase Inhibitor: Leads to Letrozole Nanoparticles for the Treatment of Breast Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200825192652 ◽

2020 ◽

Vol 20 ◽

Author(s):

Keerti Mishra ◽

Sant Kumar Verma ◽

Pooja Ratre ◽

Laxmi Banjare ◽

Abhishek Jain ◽

...

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Binding Energy ◽

Molecular Interaction ◽

In Silico ◽

Encapsulation Efficiency ◽

Drug Loading ◽

Chitosan Nanoparticles ◽

Prolonged Release

Background: It takes lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into the account for the evaluation of drug delivery ability of the chitosan nanoparticles. Objective: The present work was aimed to develop the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in-silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency was carried out. Methods: In current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically, hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. Results: Letrozole had the second highest binding affinity within the core of chitosan with MolDock (-102.470) and Rerank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. Conclusion: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment.

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