Loading and Release of Anti -Cancer Drugs Using Simultaneous pH and Temperature Responsive Nanohybrid

Abstract BackgroundTodays, drug nanocarrier development and improving its biophysical properties is one of the updated and intended of nano-biopharmaceutical science researches. Single-walled carbon nanotubes (SWCNT), as a typical carbon structure based nanocarrier, but have some obstacles in drug delivery mechanisms. In that current study, the penetration, loading, and release of Doxorubicin and Paclitaxel, as two anticancer agents, were investigated using a novel modified and functionalized SWCNT.ResultsThis study was carried out using molecular dynamics simulation based on a dual-responsive smart biomaterial. At the in-silico study, Interaction energies between drugs and carriers, numbers of hydrogen bonds, diffusion coefficient, and gyration radius were investigated. The kinetic analysis of drug adsorption and release revealed that, fascinatingly, drug loading and drug release are selective at physiological and cancerous acidic pH, respectively. Interaction of Dimethyl acryl amid-trimethyl chitosan, as a biodegradable and biocompatible hydrogel, with SWCNT indicated that degradation reaction in acidic condition destructs the polymer, which leads to a smart release in cancerous tissue at specific pH. Moreover, it resolves hydrophilicity, optimum nanoparticle size, cell membrane penetration, and cell toxicity concerns.ConclusionsThe simulation results indicated a marvelous role of dimethyl acryl amide-trimethyl chitosan in the adsorption and release of anticancer drugs in normal and neoplastic tissue. The interaction of trimethyl chitosan also improves biocompatibility as well as biodegradability of the carrier. Overall, that novel drug carrier can be a virtuous nanoparticle for loading, transporting, and releasing the anticancer drugs.

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Loading and Release of Anti-Cancer Drugs Using Simultaneous pH and Temperature Responsive Nanohybrid

10.21203/rs.3.rs-96927/v1 ◽

2020 ◽

Author(s):

Reza Maleki ◽

Mohammad Dahri ◽

Hossein Akbarialiabad

Keyword(s):

Anticancer Drugs ◽

Anticancer Agents ◽

Drug Carrier ◽

Drug Loading ◽

Dynamics Simulation ◽

Gyration Radius ◽

Neoplastic Tissue ◽

Trimethyl Chitosan ◽

Dual Responsive ◽

Adsorption And Release

Abstract Background: Todays, drug nanocarrier development and improving its biophysical properties is one of the updated and intended of nano-biopharmaceutical science researches. Single-walled carbon nanotubes (SWCNT), as a typical carbon structure based nanocarrier, but have some obstacles in drug delivery mechanisms. In that current study, the penetration, loading, and release of Doxorubicin and Paclitaxel, as two anticancer agents, were investigated using a novel modified and functionalized SWCNT.Results: This study was carried out using molecular dynamics simulation based on a dual-responsive smart biomaterial. At the in-silico study, Interaction energies between drugs and carriers, numbers of hydrogen bonds, diffusion coefficient, and gyration radius were investigated. The kinetic analysis of drug adsorption and release revealed that, fascinatingly, drug loading and drug release are selective at physiological and cancerous acidic pH, respectively. Interaction of Dimethyl acryl amid-trimethyl chitosan, as a biodegradable and biocompatible hydrogel, with SWCNT indicated that degradation reaction in acidic condition destructs the polymer, which leads to a smart release in cancerous tissue at specific pH. Moreover, it resolves hydrophilicity, optimum nanoparticle size, cell membrane penetration, and cell toxicity concerns.Conclusions: The simulation results indicated a marvelous role of dimethyl acryl amide-trimethyl chitosan in the adsorption and release of anticancer drugs in normal and neoplastic tissue. The interaction of trimethyl chitosan also improves biocompatibility as well as biodegradability of the carrier. Overall, that novel drug carrier can be a virtuous nanoparticle for loading, transporting, and releasing the anticancer drugs.

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Atomistic insight into novel co-delivery of doxorubicin and paclitaxel using fullerene modified by dimethyl acrylamide trimethyl chitosan: A computational study

10.21203/rs.3.rs-21545/v2 ◽

2020 ◽

Author(s):

Ehsan Alimohammadi ◽

Reza Maleki ◽

Hossein Akbarialiabad ◽

Mohammad Dahri

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Carrier ◽

Dynamics Simulation ◽

Gyration Radius ◽

Temperature Sensitive ◽

Trimethyl Chitosan ◽

Smart Drug ◽

Smart Drug Delivery

Abstract Background: The distribution of drugs could not be controlled in the conventional drug delivery system. This has led to the development of a smart nanoparticle-based drug delivery system, known as smart drug delivery systems. In cancer research, novel biocompatible nanocarriers have received much attention for various ranges of anticancer drugs.In the current study, the effect of a novel co-polymer "dimethyl acrylamide-trimethyl chitosan" was investigated on drug delivery of doxorubicin and paclitaxel utilizing modified fullerene nanocarrier. This study was performed via molecular dynamics simulation based on acidic pH sensitivity of the cancer microenvironment. Furthermore, hydrogen bonds, diffusion coefficient, gyration radius, and drug-carrier interaction energies were investigated here. Interestingly, a simultaneous pH and temperature-sensitive system was proposed for paclitaxel and doxorubicin for a co-polymer. A pH-sensitive and temperature-sensitive copolymer was used based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent option to have two properties in one bio-polymer. Results: The results suggest the dramatic and indisputable role of the co-polymer in the release of doxorubicin and paclitaxel in cancerous tissues, as well as an increased biocompatibility and drug uptake in a neutral state. The validation test was performed by repeated simulations of a similar article. The results are very close to those of the reference paper .Conclusions: Overall, conjugated fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as carriers can be a good proposition for loading, delivery, and release of anti-cancer drugs based on a pH/temperature-sensitive smart drug delivery system.

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Novel pH-Responsive Nanohybrid for Stimultaneous Delivery of Doxorubicin and Paclitaxel: An In-Silico Insight

10.21203/rs.3.rs-96912/v1 ◽

2020 ◽

Author(s):

Ehsan Alimohammadi ◽

Reza Maleki ◽

Hossein Akbarialiabad ◽

Mohammad Dahri

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Carrier ◽

Dynamics Simulation ◽

Gyration Radius ◽

Temperature Sensitive ◽

Trimethyl Chitosan ◽

Smart Drug ◽

Smart Drug Delivery

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Atomistic insight into novel co-delivery of doxorubicin and paclitaxel using fullerene modified by dimethyl acrylamide trimethyl chitosan: A computational study

10.21203/rs.3.rs-21545/v1 ◽

2020 ◽

Author(s):

Ehsan Alimohammadi ◽

Reza Maleki ◽

Hossein Akbarialiabad ◽

Mohammad Dahri

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Carrier ◽

Dynamics Simulation ◽

Gyration Radius ◽

Temperature Sensitive ◽

Trimethyl Chitosan ◽

Smart Drug ◽

Smart Drug Delivery

Abstract Background: The distribution of drugs could not be controlled in the conventional drug delivery system. This has led to the development of a smart nanoparticle-based drug delivery system, known as smart drug delivery systems. In cancer research, novel biocompatible nanocarriers have received much attention for various ranges of anticancer drugs.In the current study, the effect of a novel co-polymer "dimethyl acrylamide-trimethyl chitosan" was investigated on drug delivery of doxorubicin and paclitaxel utilizing modified fullerene nanocarrier. This study was performed via molecular dynamics simulation based on acidic pH sensitivity of the cancer microenvironment. Furthermore, hydrogen bonds, diffusion coefficient, gyration radius, and drug-carrier interaction energies were investigated here. Interestingly, a simultaneous pH and temperature-sensitive system was proposed for paclitaxel and doxorubicin for a co-polymer. A pH-sensitive and temperature-sensitive copolymer was used based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent option to have two properties in one bio-polymer.Results: The results suggest the dramatic and indisputable role of the co-polymer in the release of doxorubicin and paclitaxel in cancerous tissues, as well as an increased biocompatibility and drug uptake in a neutral state. The validation test was performed by repeated simulations of a similar article. The results are very close to those of the reference paper.Conclusions: Overall, conjugated fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as carriers can be a good proposition for loading, delivery, and release of anti-cancer drugs based on a pH/temperature-sensitive smart drug delivery system.

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Novel pH-responsive nanohybrid for simultaneous delivery of doxorubicin and paclitaxel: an in-silico insight

BMC Chemistry ◽

10.1186/s13065-021-00735-4 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Ehsan Alimohammadi ◽

Reza Maleki ◽

Hossein Akbarialiabad ◽

Mohammad Dahri

Keyword(s):

Drug Delivery ◽

Delivery System ◽

Drug Loading ◽

Delivery Systems ◽

Dynamics Simulation ◽

Radius Of Gyration ◽

Ph Responsive ◽

Trimethyl Chitosan ◽

Smart Drug ◽

Smart Drug Delivery

Abstract Background The distribution of drugs could not be controlled in the conventional delivery systems. This has led to the developing of a specific nanoparticle-based delivery system, called smart drug delivery systems. In cancer therapy, innovative biocompatible nanocarriers have received much attention for various ranges of anti-cancer drugs. In this work, the effect of an interesting and novel copolymer named "dimethyl acrylamide-trimethyl chitosan" was investigated on delivery of paclitaxel and doxorubicin applying carboxylated fullerene nanohybrid. The current study was run via molecular dynamics simulation and quantum calculations based on the acidic pH differences between cancerous microenvironment and normal tissues. Furthermore, hydrogen bonds, radius of gyration, and nanoparticle interaction energies were studied here. Stimulatingly, a simultaneous pH and temperature-responsive system were proposed for paclitaxel and doxorubicin for a co-polymer. A pH-responsive and thermal responsive copolymer were utilized based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent system to possess two simultaneous properties in one bio-polymer. Results The simulation results proposed dramatic and indisputable effects of the copolymer in the release of drugs in cancerous tissues, as well as increased biocompatibility and drug uptake in healthy tissues. Repeated simulations of a similar article performed for the validation test. The results are very close to those of the reference paper. Conclusions Overall, conjugated modified fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as nanohybrid can be an appropriate proposition for drug loading, drug delivery, and drug release on dual responsive smart drug delivery system.

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Chitosan-based Polymer Matrix for Pharmaceutical Excipients and Drug Delivery

Current Medicinal Chemistry ◽

10.2174/0929867325666180927100817 ◽

2019 ◽

Vol 26 (14) ◽

pp. 2502-2513 ◽

Cited By ~ 9

Author(s):

Md. Iqbal Hassan Khan ◽

Xingye An ◽

Lei Dai ◽

Hailong Li ◽

Avik Khan ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Drug Carrier ◽

Drug Loading ◽

Delivery Systems ◽

Cancer Drug ◽

Release Mechanism ◽

Innovative Drug ◽

Pharmaceutical Excipients ◽

Weight Variation

The development of innovative drug delivery systems, versatile to different drug characteristics with better effectiveness and safety, has always been in high demand. Chitosan, an aminopolysaccharide, derived from natural chitin biomass, has received much attention as one of the emerging pharmaceutical excipients and drug delivery entities. Chitosan and its derivatives can be used for direct compression tablets, as disintegrant for controlled release or for improving dissolution. Chitosan has been reported for use in drug delivery system to produce drugs with enhanced muco-adhesiveness, permeation, absorption and bioavailability. Due to filmogenic and ionic properties of chitosan and its derivative(s), drug release mechanism using microsphere technology in hydrogel formulation is particularly relevant to pharmaceutical product development. This review highlights the suitability and future of chitosan in drug delivery with special attention to drug loading and release from chitosan based hydrogels. Extensive studies on the favorable non-toxicity, biocompatibility, biodegradability, solubility and molecular weight variation have made this polymer an attractive candidate for developing novel drug delivery systems including various advanced therapeutic applications such as gene delivery, DNA based drugs, organ specific drug carrier, cancer drug carrier, etc.

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Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

Current Medicinal Chemistry ◽

10.2174/0929867326666191016151018 ◽

2019 ◽

Vol 26 ◽

Cited By ~ 1

Author(s):

Agnieszka Wróbel ◽

Danuta Drozdowska

Keyword(s):

Anticancer Activity ◽

Anticancer Drugs ◽

Anticancer Agents ◽

Physicochemical Characterization ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Biological Research ◽

Structure Activity ◽

Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

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Nanostructured Lipid Carriers (NLCs) for drug delivery: Role of Liquid lipid (oil)

Current Drug Delivery ◽

10.2174/1567201817666200423083807 ◽

2020 ◽

Vol 17 ◽

Author(s):

Anisha D’Souza ◽

Ranjita Shegokar

Keyword(s):

Drug Delivery ◽

Essential Oils ◽

Drug Carrier ◽

Drug Loading ◽

Performance Criteria ◽

Long Term Stability ◽

Natural Oils ◽

Optimal Drug

: In recent years, SLNs and NLCs are among the popular drug delivery systems studied for delivery of lipophilic drugs. Both systems have demonstrated several beneficial properties as an ideal drug-carrier, optimal drug-loading and good long-term stability. NLCs are getting popular due to their stability advantages and possibility to load various oil components either as an active or as a matrix. This review screens types of oils used till date in combination with solid lipid to form NLCs. These oils are broadly classified in two categories: Natural oils and Essential oils. NLCs offer range advantages in drug delivery due to the formation of imperfect matrix owing to the presence of oil. The type and percentage of oil used determines optimal drug loading and stability. Literature shows that variety of oils is used in NLCs mainly as matrix, which is from natural origin, triglycerides class. On the other hand, essential oils not only serve as a matrix but as an active. In short, oil is the key ingredient in formation of NLCs, hence needs to be selected wisely as per the performance criteria expected.

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Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170911170104 ◽

2018 ◽

Vol 18 (2) ◽

pp. 302-311

Author(s):

Shulin Dai ◽

Yucheng Feng ◽

Shuyi Li ◽

Yuxiao Chen ◽

Meiqing Liu ◽

...

Keyword(s):

Glutamic Acid ◽

Drug Carrier ◽

Drug Loading ◽

Drug Carriers ◽

Cancer Drug ◽

Drug Release Profile ◽

Sustained Drug Release ◽

Anti Cancer ◽

Physical Interactions

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. </P><P> Aims/Methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

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