scholarly journals An Integrated Multiscale Mechanistic Model for Cancer Drug Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lei Tang ◽  
Jing Su ◽  
De-Shuang Huang ◽  
Daniel Y. Lee ◽  
King C. Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Therapy ◽  
Mechanistic Model ◽  
Scale Model ◽  
Distribution Model ◽  
Cancer Drug ◽  
Therapeutic Effects ◽  
Antitumor Effects ◽  
Combination Drug ◽  
Drug Concentrations

In this paper, we established a multiscale mechanistic model for studying drug delivery, biodistribution, and therapeutic effects of cancer drug therapy in order to identify optimal treatment strategies. Due to the specific characteristics of cancer, our proposed model focuses on drug effects on malignant solid tumor and specific internal organs as well as the intratumoral and regional extracellular microenvironments. At the organ level, we quantified drug delivery based on a multicompartmental model. This model will facilitate the analysis and prediction of organ toxicity and provide important pharmacokinetic information with regard to drug clearance rates. For the analysis of intratumoral microenvironment which is directly related to blood drug concentrations and tumor properties, we constructed a drug distribution model using diffusion-convection solute transport to study temporal/spatial variations of drug concentration. With this information, our model incorporates signaling pathways for the analysis of antitumor response with drug combinations at the extracellular level. Moreover, changes in tumor size, cellular proliferation, and apoptosis induced by different drug treatment conditions are studied. Therefore, the proposed multi-scale model could be used to understand drug clinical actions, study drug therapy-antitumor effects, and potentially identify optimal combination drug therapy. Numerical simulations demonstrate the proposed system's effectiveness.

scholarly journals SCIDOT-18. NANOTHERAPEUTICS FOR NEUROSURGICALLY-APPLIED DRUG DELIVERY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi275-vi275
Author(s):  
Catherine Vasey ◽  
Vincenzo Taresco ◽  
Stuart Smith ◽  
Cameron Alexander ◽  
Ruman Rahman
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
Drug Formulation ◽  
Local Drug Delivery ◽  
Resection Margins ◽  
Therapeutic Drug ◽  
Tumour Resection ◽  
Combination Drug ◽  
Drug Encapsulation ◽  
Drug Concentrations

Abstract Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to deliver a mucoadhesive hydrogel containing chemotherapeutic nanoparticles (NPs) into the tumour resection margins. The overall aim is to spray a NP and polymer solution onto the resection cavity and potentially increase penetration of anti-cancer drugs within the 2 cm reoccurrence zone beyond the infiltrative margin. The mucoadhesive gel of choice, pectin, is currently used in other in vivo applications; however we have repurposed this for the brain. Pectin is biocompatible with GBM and human astrocyte cells in vitro and showed neither toxicity nor inflammation for up to 2 weeks upon orthotopic brain injection. Pectin is biodegradable in artificial CSF and is capable of being sprayed from the engineered device. A panel of polymeric, oil-based and polymer-coated NPs have been developed and optimised to maximise drug encapsulation of etoposide and olaparib as proof-of-concept for combination drug delivery. Etoposide/olaparib was chosen due to cytotoxicity from 5 GBM cell lines, including primary lines isolated from the invasive tumour margin (Mean IC50 of 1.1 µM and 8.3 µM respectively). The optimal NP/drug formulation (based on drug encapsulation, spray capability and bio-adhesiveness) will ultimately be assessed for tolerability and efficacy using orthotopic allograft and xenograft high-grade glioma models, including measurement of penetration of drug/nanoparticle in ex vivo murine and porcine brain using novel hybrid time-of-flight/Orbitrap TM secondary ion mass spectrometer (orbiSIMS) technology.

scholarly journals EXTH-25. A MECHANICALLY-ENGINEERED SPRAY TO INCREASE BRAIN PENETRATION OF CHEMOTHERAPEUTIC NANOPARTICLES IN THE TREATMENT OF HIGH GRADE GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi87-vi87
Author(s):  
Phoebe McCrorie ◽  
Vincenzo Taresco ◽  
Alison Ritchie ◽  
Phillip Clarke ◽  
David Scurr ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Formulation ◽  
Local Drug Delivery ◽  
Resection Margins ◽  
Therapeutic Drug ◽  
Tumour Resection ◽  
High Grade ◽  
Combination Drug ◽  
Drug Encapsulation ◽  
Drug Concentrations

Abstract Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to deliver a mucoadhesive hydrogel containing chemotherapeutic nanoparticles (NPs) into the tumour resection margins. The overall aim is to spray a NP and polymer solution onto the resection cavity and potentially increase penetration of anti-cancer drugs within the 2 cm reoccurrence zone beyond the infiltrative margin. The mucoadhesive gel of choice, pectin, is currently used in other in vivo applications; however we have repurposed this for the brain. Pectin is biocompatible with GBM and human astrocyte cells in vitro and showed neither toxicity nor inflammation for up to 2 weeks upon orthotopic brain injection. Pectin is biodegradable in artificial CSF and is capable of being sprayed from the engineered device. A panel of polymeric, oil-based and polymer-coated NPs have been developed and optimised to maximise drug encapsulation of etoposide and olaparib as proof-of-concept for combination drug delivery. Etoposide/olaparib were chosen due to cytotoxicity from 5 GBM cell lines, including primary lines isolated from the invasive tumour margin (Mean IC50 of 1.1 µM and 8.3 µM respectively). The optimal NP/drug formulation (based on drug encapsulation, spray capability and bio-adhesiveness) will ultimately be assessed for tolerability and efficacy using orthotopic allograft and xenograft high-grade glioma models, including measurement of penetration of drug/nanoparticle in ex vivo murine and porcine brain using novel hybrid time-of-flight/Orbitrap TM secondary ion mass spectrometer (orbiSIMS) technology.

scholarly journals A mechanically-engineered spray to increase brain penetration of chemotherapeutic nanoparticles in the treatment of high-grade gliomas

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv1-iv1
Author(s):  
Phoebe McCrorie ◽  
Vincenco Taresco ◽  
Zeyuan Xu ◽  
Alison Ritchie ◽  
Phillip Clarke ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Formulation ◽  
Local Drug Delivery ◽  
Resection Margins ◽  
Therapeutic Drug ◽  
Tumour Resection ◽  
High Grade ◽  
Combination Drug ◽  
Drug Encapsulation ◽  
Drug Concentrations

Abstract Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to deliver a mucoadhesive hydrogel containing chemotherapeutic nanoparticles (NPs) into the tumour resection margins. The overall aim is to spray a NP and polymer solution onto the resection cavity and potentially increase penetration of anti-cancer drugs within the 2 cm reoccurrence zone beyond the infiltrative margin. The mucoadhesive gel of choice, pectin, is currently used in other in vivo applications; however we have repurposed this for the brain. Pectin is biocompatible with GBM and human astrocyte cells in vitro and showed neither toxicity nor inflammation for up to 2 weeks upon orthotopic brain injection. Pectin is biodegradable in artificial CSF and is capable of being sprayed from the engineered device. A panel of polymeric, oil-based and polymer-coated NPs have been developed and optimised to maximise drug encapsulation of etoposide and olaparib as proof-of-concept for combination drug delivery. Etoposide/olaparib was chosen due to cytotoxicity from 5 GBM cell lines, including primary lines isolated from the invasive tumour margin (Mean IC50 of 1.1 µM and 8.3 µM respectively). The optimal NP/drug formulation (based on drug encapsulation, spray capability and bio-adhesiveness) will ultimately be assessed for tolerability and efficacy using orthotopic allograft and xenograft high-grade glioma models.

scholarly journals SCIDOT-19. A MECHANICALLY-ENGINEERED SPRAY TO INCREASE BRAIN PENETRATION OF CHEMOTHERAPEUTIC NANOPARTICLES IN THE TREATMENT OF HIGH-GRADE GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi275-vi275
Author(s):  
Phoebe McCrorie ◽  
Vincenzo Taresco ◽  
Zeyuan Xu ◽  
Alison Ritchie ◽  
Philip A Clarke ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Formulation ◽  
Local Drug Delivery ◽  
Resection Margins ◽  
Therapeutic Drug ◽  
Tumour Resection ◽  
High Grade ◽  
Combination Drug ◽  
Drug Encapsulation ◽  
Drug Concentrations

Abstract Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to deliver a mucoadhesive hydrogel containing chemotherapeutic nanoparticles (NPs) into the tumour resection margins. The overall aim is to spray a NP and polymer solution onto the resection cavity and potentially increase penetration of anti-cancer drugs within the 2 cm reoccurrence zone beyond the infiltrative margin. The mucoadhesive gel of choice, pectin, is currently used in other in vivo applications; however we have repurposed this for the brain. Pectin is biocompatible with GBM and human astrocyte cells in vitro and showed neither toxicity nor inflammation for up to 2 weeks upon orthotopic brain injection. Pectin is biodegradable in artificial CSF and is capable of being sprayed from the engineered device. A panel of polymeric, oil-based and polymer-coated NPs have been developed and optimised to maximise drug encapsulation of etoposide and olaparib as proof-of-concept for combination drug delivery. Etoposide/olaparib was chosen due to cytotoxicity from 5 GBM cell lines, including primary lines isolated from the invasive tumour margin (Mean IC50 of 1.1 µM and 8.3 µM respectively). The optimal NP/drug formulation (based on drug encapsulation, spray capability and bio-adhesiveness) will ultimately be assessed for tolerability and efficacy using orthotopic allograft and xenograft high-grade glioma models, including measurement of penetration of drug/nanoparticle in ex vivo murine and porcine brain using novel hybrid time-of-flight/Orbitrap TM secondary ion mass spectrometer (orbiSIMS) technology.

Doxorubicin Loaded Nanoparticle Consisting of Chitosan and Mannose Modified Graphene Oxide for Intracellular Drug Delivery and Anti-tumor Activity

2020 ◽  
Vol 13 (5) ◽  
pp. 5155-5164
Author(s):  
Meena K. S. ◽  
Sonia K ◽  
Alamelu Bai S
Keyword(s):  
Drug Delivery ◽  
Graphene Oxide ◽  
Drug Delivery System ◽  
Delivery System ◽  
In Vitro Release ◽  
Cancer Drug ◽  
Hemolysis Assay ◽  
Functionalized Graphene Oxide ◽  
Intracellular Drug Delivery ◽  
Modified Graphene Oxide

In order to develop the efficiency and the specificity of anticancer drug delivery, we have designed an innovative nanocarrier. The nanocarrier system comprises of a multifunctional graphene oxide nanoparticle-based drug delivery system (GO-CS-M-DOX) as a novel platform for intracellular drug delivery of doxorubicin (DOX). Firstly, graphene oxide (GO) was synthesized by hummer’s method whose surface was functionalized by chitosan (CS) in order to obtain a more precise drug delivery, the system was then decorated with mannose (M). Further conjugation of an anti-cancer drug doxorubicin to the nanocarrier system resulted in GO-CS-M-DOX drug delivery system. The resultant conjugate was characterized for its physio-chemical properties and its biocompatibility was evaluated via hemolysis assay. The drug entrapment efficiency is as high as 90% and in vitro release studies of DOX under pH 5.3 is significantly higher than that under pH 7.4. The anticancer activity of the synthesized drug delivery system was studied by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay against MCF-7 cell line. These results stated that the pH dependent multifunctional doxorubicin- chitosan functionalized graphene oxide based nanocarrier system, could lead to a promising and potential platform for intracellular delivery and cytotoxicity activity for variety of anticancer drugs.   

Chitosan-based Polymer Matrix for Pharmaceutical Excipients and Drug Delivery

2019 ◽  
Vol 26 (14) ◽  
pp. 2502-2513 ◽  
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.

Self-Assembled Nanocarriers Based on Amphiphilic Natural Polymers for Anti- Cancer Drug Delivery Applications

2018 ◽  
Vol 23 (35) ◽  
Author(s):  
Sally Sabra ◽  
Mona Abdelmoneem ◽  
Mahmoud Abdelwakil ◽  
Moustafa Taha Mabrouk ◽  
Doaa Anwar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Drug ◽  
Natural Polymers ◽  
Anti Cancer ◽  
Drug Delivery Applications ◽  
Self Assembled ◽  
Cancer Drug Delivery
Sign in / Sign up

Export Citation Format

Share Document