Nanoparticles-in-soft microagglomerates as oral colon-specific cancer therapeutic vehicle

2021 ◽  
Author(s):  
Nafisah Musa ◽  
Tin Wui Wong
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Colon Cancer ◽  
Drug Release ◽  
Primary Therapy ◽  
Specific Drug ◽  
Nanoparticle Aggregation ◽  
Cancer Chemotherapeutics ◽  
Colon Specific Drug Delivery ◽  
Upper Gastrointestinal

Polymeric nanoparticles can be conjugated with targeting ligand such as folate to elicit oral colon-specific drug delivery to treat colon cancer. Oral chemotherapy can be used as adjuvant, neo-adjuvant, or primary therapy. Nonetheless, oral cancer chemotherapeutics may experience premature drug release at the upper gastrointestinal tract due to the availability of a large specific dissolution surface area of nanoparticles leading to failure in colon cancer targeting. This study designed soft microagglomerates as carrier of nanoparticles to delay drug release. High molecular weight chitosan/pectin with covalent 5-fluorouracil/folate was processed into nanoparticles. Low molecular weight chitosan was spray-dried into nanoparticle aggregation vehicle. The soft agglomerates were produced by blending of nanoparticles and aggregation vehicle in specific weight ratios through vortex method. Adding aggregation vehicle promoted soft agglomeration with nanoparticles deposited onto its surfaces with minimal binary coalescence. Soft agglomerates prepared from 10:18 weight ratio of nanoparticles to nanoparticle aggregation vehicle using 1% chitosan solution concentration reduced the propensity of premature drug release of nanoparticles in the upper gastrointestinal region. Soft agglomerates reduced early drug release of cancer chemotherapeutics and was responsive to intracapsular sodium alginate coat to further sustain drug release. The soft microagglomerates are a viable dosage form in colon-specific drug delivery. Further study will focus on investigating intracapsular-coated soft agglomerates in vivo pharmacokinetics and pharmacodynamics behaviours with respect to local colorectal cancer.

scholarly journals Development and evaluation of colon targeted drug delivery system by using natural Polysaccharides/Polymers

2015 ◽  
Vol 13 (1) ◽  
pp. 105-113 ◽  
Author(s):  
GR Godge ◽  
SN Hiremath
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Ethyl Cellulose ◽  
Xanthan Gum ◽  
Guar Gum ◽  
Specific Drug ◽  
Metoprolol Succinate ◽  
Colon Specific Drug Delivery ◽  
Enteric Coated ◽  
Upper Gastrointestinal

Colon is being extensively investigated as a drug delivery site. This study contains comparison of the usual enteric coating polymers viz. xanthan gum, guar gum, chitosan and ethyl cellulose, as carriers for colon specific drug delivery. Lactose based metoprolol succinate tablets were prepared. These were coated with one of the coating polymers to a varying coat thickness. Tablets were prepared using polysaccharides or synthetic polymer as binders. These included xanthan gum, guar gum, chitosan and ethyl cellulose. Metoprolol Succinate was used as a model drug. The prepared tablets were enteric coated with kollicoat MAE 100 DP to give protection in the stomach. The coated tablets were tested in-vitro for their suitability as colon specific drug delivery systems. The drug release studies were carried out in simulated stomach environment (pH 1.2) for 2 h followed by small intestinal environment at pH 6.8. The dissolution data obtained from tablets demonstrates that the dissolution rate of the tablet is dependent upon the type and concentration of polysaccharide/polymer used as binder. The results demonstrate that enteric coated tablets containing 3% chitosan as a binder, showed only 12.5% drug release in the first 5 h, which is the usual upper gastrointestinal transit time, whereas, tablets prepared using guar gum as binder, were unable to protect drug release under similar conditions. Preparations with xanthan gum as a binder formed time-dependent release formulations. When used in a concentration of 5.92% in the tablets, 28% drug release was observed in the usual upper gastrointestinal tract conditions. It was also found that enteric coated preparation formulated with 8.88% of kollicoat MAE 100 DP as binder could be used to carry water insoluble drug molecules. The above study shows that chitosan could be successfully used as a binder, for colon targeting of water insoluble drugs in preference to guar gum when used in the same concentration. Additionally, formulations developed with chitosan and kollicoat MAE 100 DP would be highly site specific since drug release would be at a retarded rate till microbial degradation or polymer solubilization takes place in the colon. DOI: http://dx.doi.org/10.3329/dujps.v13i1.21874 Dhaka Univ. J. Pharm. Sci. 13(1): 105-113, 2014 (June)

scholarly journals Synthesis, in-vitro characterization and pharmacological evaluation of conjugates of flurbiprofen and polysaccharides for colon specific drug delivery

2019 ◽  
Vol 9 (2) ◽  
pp. 316-320
Author(s):  
P Soni ◽  
K Soni ◽  
GP Choudhary
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Specific Drug ◽  
Glycosidic Linkage ◽  
In Vitro Drug Release ◽  
In Vitro Characterization ◽  
Microbial System ◽  
Colon Specific Drug Delivery ◽  
Upper Gastrointestinal

The aim of the study was to prepare site specific drug delivery of flurbiprofen using polysaccharides by the formation of glycosidic linkage which is hydrolysed by the microflora present in colon. This approach prevents drug release in the upper gastrointestinal environment. Due to the minimal degradation of conjugates in upper Git, the in vitro drug release in SGF, SIF and SCF was found upto 4.26±0.03%, 12.41±0.08% and 92.72±3.33% respectively. Keywords: Colon specific drug delivery, Conjugates, Flurbiprofen, Microbial system.

scholarly journals Chitosan-capped enzyme-responsive hollow mesoporous silica nanoplatforms for colon-specific drug delivery

2020 ◽  
Author(s):  
Defu Cai ◽  
Cuiyan Han ◽  
Chang Liu ◽  
Xiaoxing Ma ◽  
Jiayi Qian ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Mesoporous Silica ◽  
Specific Drug ◽  
Hollow Mesoporous Silica Spheres ◽  
Good Biocompatibility ◽  
Colon Specific Drug Delivery ◽  
Loading Amount ◽  
Hollow Mesoporous Silica

Abstract An enzyme-responsive colon-specific delivery system was developed based on hollow mesoporous silica spheres (HMSS) to which biodegradable chitosan (CS) was attached via cleavable azo bonds (HMSS-N=N-CS). Doxorubicin (DOX) was encapsulated in a noncrystalline state in the hollow cavity and mesopores of HMSS with the high loading amount of 35.2%. In vitro drug release proved that HMSS-N=N-CS/DOX performed enzyme-responsive drug release. The grafted CS could increase the biocompatibility and stability, and reduce the protein adsorption on HMSS. Gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS-N=N-CS. Cellular uptake results indicated that the uptake of DOX was obviously increased after HMSS-N=N-CS/DOX was preincubated with a colonic enzyme mixture. HMSS-N=N-CS/DOX incubated with colon enzymes showed increased cytotoxicity, and its IC 50 value was three times lower than that of HMSS-N=N-CS/DOX group without colon enzymes. The present work lays the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.

scholarly journals Chitosan capping enzyme-responsive hollow mesoporous silica nanoplatforms for colon specific drug delivery

2020 ◽  
Author(s):  
Defu Cai ◽  
Cuiyan Han ◽  
Chang Liu ◽  
Xiaoxing Ma ◽  
Jiayi Qian ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Mesoporous Silica ◽  
Laser Scanning ◽  
Confocal Laser Scanning Microscope ◽  
Confocal Laser ◽  
Specific Drug ◽  
Colon Specific Drug Delivery ◽  
Hollow Mesoporous Silica

Abstract In summary, an enzyme-responsive colon specific drug delivery system was developed based on hollow mesoporous silica sphere (HMSS), in which the biodegradable chitosan (CS) was gated on the openings of HMSS through cleavable azo bonds (HMSS-N=N-CS). Doxorubicin (DOX) was encapsulated into the hollow cavity and mesopores of HMSS, and HMSS-N=N-CS/DOX showed a high loading amount of 35.2%. X-ray diffraction (XRD) experiment proved that the DOX loaded in the HMSS-N=N-CS was in a non–crystalline state. In vitro drug release experiments proved that HMSS-N=N-CS/DOX showed an enzyme-responsive drug release property. The grafted CS could increase the biocompatibility and stability of HMSS, and reduce the protein adsorption on the surface of HMSS. The gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS-N=N-CS. The confocal laser scanning microscope (CLSM) and flow cytometry technique (FCM) results indicated that the cellular uptake of DOX was obviously increased after the HMSS-N=N-CS/DOX was preincubated with colonic enzyme mixture. Cell viability result indicated that HMSS-N=N-CS/DOX incubated with colon enzyme showed an increased cytotoxicity and the IC50 value was three time less than that of HMSS-N=N-CS/DOX group. The present work will lay the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.

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