Abstract:An
injectable hydrogel-based drug delivery carrier has been developed
for long-term drug release by assembling various generations of cyclodextrin
(CD) followed by hydrophobic layers to control the drug release for
effective cancer treatment. Three generations of CD are designed through
urethane linkages using small spacers to create a large hydrophilic
core, which is covered with hydrophobic layers of polyurethane through
grafting to maintain the hydrophilic hydrophobic balance of the whole
superstructure. Dr… Show more
“…The degree of grafting is calculated from the integrated peak area under the peaks and is found to be 15% for D-P-L (low graft density) to 30% in D-P-H (high graft density). 34 The peaks between δ = 4.46 and 4.67 ppm are attributed to protons at positions 2, 3, 4, 5, and 6 (H 2 to H 6 ) while the peak at 5.15 ppm is due to anomeric protons. The peaks indicate the existence of hydroxyl protons -OH (2) and -OH (3, 4, 6), respectively.…”
Section: Resultsmentioning
confidence: 98%
“…Hydrophilic poly(ethylene oxide) based PU hydrogels have been synthesized and have presented with the desired characteristics that can be used for drug-delivery applications. 33,34 Grafting of polyurethanes on dextrin can be a new frontier for developing biodegradable and biocompatible polymers, utilizing them as drug-delivery carrier by tuning the hydrophobic wrapping on hydrophilic moiety. Interest lies in investigation of novel chemically linked, biocompatible graft copolymer for sustained drug-delivery applications.…”
Novel biocompatible and brush copolymers have been developed for cancer treatment using its controlled drug-release potential. Polyurethane graft on linear dextrin has been synthesized to control the hydrophilic–hydrophobic balance for regulated drug delivery. The properties of the graft copolymers have been tuned through graft density. The prepared grafts are thermally stable and mechanically strong. An injectable hydrogel has been developed by embedding the drug-loaded brush copolymers in methyl cellulose to better control the release for a prolonged period, importantly by keeping the drug release at a constant rate. Cellular studies indicate the biocompatible nature of the brush copolymers whose controlled and slow release of drug exhibit significant cytotoxic effects on cancer cells. Endocytosis of drug tagged contrast agent indicates greater transport of biologically active material inside cell as observed through cellular uptake studies. In vivo studies on melanoma mice exhibit the real efficacy of the controlled drug release from the injectable hydrogel with significant melanoma suppression without any side effects as opposed to severe toxic effects observed in conventional chemotherapy. Special application method of drug-loaded hydrogel just beneath the tumor makes this system incredibly effective through confinement. Thus, brush copolymer injectable hydrogel is a promising vehicle for control release of drug for cancer treatment in future.
“…The degree of grafting is calculated from the integrated peak area under the peaks and is found to be 15% for D-P-L (low graft density) to 30% in D-P-H (high graft density). 34 The peaks between δ = 4.46 and 4.67 ppm are attributed to protons at positions 2, 3, 4, 5, and 6 (H 2 to H 6 ) while the peak at 5.15 ppm is due to anomeric protons. The peaks indicate the existence of hydroxyl protons -OH (2) and -OH (3, 4, 6), respectively.…”
Section: Resultsmentioning
confidence: 98%
“…Hydrophilic poly(ethylene oxide) based PU hydrogels have been synthesized and have presented with the desired characteristics that can be used for drug-delivery applications. 33,34 Grafting of polyurethanes on dextrin can be a new frontier for developing biodegradable and biocompatible polymers, utilizing them as drug-delivery carrier by tuning the hydrophobic wrapping on hydrophilic moiety. Interest lies in investigation of novel chemically linked, biocompatible graft copolymer for sustained drug-delivery applications.…”
Novel biocompatible and brush copolymers have been developed for cancer treatment using its controlled drug-release potential. Polyurethane graft on linear dextrin has been synthesized to control the hydrophilic–hydrophobic balance for regulated drug delivery. The properties of the graft copolymers have been tuned through graft density. The prepared grafts are thermally stable and mechanically strong. An injectable hydrogel has been developed by embedding the drug-loaded brush copolymers in methyl cellulose to better control the release for a prolonged period, importantly by keeping the drug release at a constant rate. Cellular studies indicate the biocompatible nature of the brush copolymers whose controlled and slow release of drug exhibit significant cytotoxic effects on cancer cells. Endocytosis of drug tagged contrast agent indicates greater transport of biologically active material inside cell as observed through cellular uptake studies. In vivo studies on melanoma mice exhibit the real efficacy of the controlled drug release from the injectable hydrogel with significant melanoma suppression without any side effects as opposed to severe toxic effects observed in conventional chemotherapy. Special application method of drug-loaded hydrogel just beneath the tumor makes this system incredibly effective through confinement. Thus, brush copolymer injectable hydrogel is a promising vehicle for control release of drug for cancer treatment in future.
“…UV−visible spectra of pure chitosan, prepolymer (PU) and graft copolymer are shown in Figure 1c. Pure chitosan and PU show absorption peaks at 305 and 290 nm, respectively, for the n → π* transition, 51,52 whereas the graft copolymer shows an absorption band at higher wavelength (333 nm), suggesting good interaction between PU and CHT. The graft copolymer shows the hydrophobic nature after grafting of an hydrophobic PU component on the hydrophilic chitosan backbone as observed from the contact angle measurement showing higher contact angle for CHTPU (69°) as compared to pure CHT (56°) (Figure 1d).…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…UV–visible spectra of pure chitosan, prepolymer (PU) and graft copolymer are shown in Figure c. Pure chitosan and PU show absorption peaks at 305 and 290 nm, respectively, for the n → π* transition, , whereas the graft copolymer shows an absorption band at higher wavelength (333 nm), suggesting good interaction between PU and CHT.…”
An injectable hydrogel of chemically modified chitosan has been developed for controlled drug delivery application. Highly hydrophilic chitosan is chemically modified through grafting of ester-diol based polyurethane to transform into hydrogel through hydrophilic−hydrophobic balance. Grafting is confirmed through different spectroscopic techniques such as 13 C NMR, UV− visible, and FTIR. Grafted copolymer shows higher contact angle as well as poorer swelling than pure one. Hydrogel of graft copolymer is made in dilute acetic acid medium. Surface morphology of the hydrogel, as investigated through SEM, exhibits an interconnected porous network suitable for drug delivery vehicle. In vitro drug release kinetics reveals that the graft copolymer releases the drug in a sustained manner as compared to the pure one. Two types of model drugs (antibacterial tetracycline hydrochloride and anticancerous doxorubicin hydrochloride) are used for release study to check the control release for various applications. The cytotoxicity of the newly developed hydrogel is accessed using the B16−F10 melanoma cell line, and the hydrogel is found to have a better biocompatible nature than that of pure chitosan. Cellular uptake of drug from graft copolymer hydrogel has considerably increased vis-a-vis pure drug resulting in significant enhancement of cell killing using the developed drug embedded hydrogel system. In vivo gelation study in an animal model verifies that the graft copolymer has the fine ability to be used as an injectable hydrogel for disease control. Hence, the developed graft copolymer has the potential to be used as an injectable hydrogel as a controlled drug delivery vehicle.
“…8h). 256 Therefore, complete melanoma shrinkage with higher biodistribution of the drug through a gel placed subcutaneously is an effective carrier for cancer treatment. However, drugs embedded in nanoparticles, whether inorganic or organic, exhibit sustained drug release and thereby exhibit much greater therapeutic effects than the pure drug.Fig.…”
Section: Application Of Various Nanocarriers For Diagnosis and Treatmentmentioning
The application of nanomedicines is increasing rapidly with the promise of targeted and efficient drug delivery. Nanomedicines address the shortcomings of conventional therapy, as evidenced by several preclinical and clinical investigations indicating sitespecific drug delivery, reduced side effects, and better treatment outcome. The development of suitable and biocompatible drug delivery vehicles is a prerequisite that has been successfully achieved by using simple and functionalized liposomes, nanoparticles, hydrogels, micelles, dendrimers, and mesoporous particles. A variety of drug delivery vehicles have been established for the targeted and controlled delivery of therapeutic agents in a wide range of chronic diseases, such as diabetes, cancer, atherosclerosis, myocardial ischemia, asthma, pulmonary tuberculosis, Parkinson's disease, and Alzheimer's disease. After successful outcomes in preclinical and clinical trials, many of these drugs have been marketed for human use, such as Abraxane®, Caelyx®, Mepact®, Myocet®, Emend®, and Rapamune®. Apart from drugs/compounds, novel therapeutic agents, such as peptides, nucleic acids (DNA and RNA), and genes have also shown potential to be used as nanomedicines for the treatment of several chronic ailments. However, a large number of extensive clinical trials are still needed to ensure the short-term and long-term effects of nanomedicines in humans. This review discusses the advantages of various drug delivery vehicles for better understanding of their utility in terms of current medical needs. Furthermore, the application of a wide range of nanomedicines is also described in the context of major chronic diseases.
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