- Efficacy of polyurethane graft on cyclodextrin to control drug release for tumor treatment. [Journal Article]
- JCJ Colloid Interface Sci 2018 Sep 11; 534:215-227
- Hydrophilicity of cyclodextrin is controlled through grafting of polyurethane of varying graft density, thereby maintain the hydrophilic-hydrophobic balance, to sustain the drug delivery rate for bet...
Hydrophilicity of cyclodextrin is controlled through grafting of polyurethane of varying graft density, thereby maintain the hydrophilic-hydrophobic balance, to sustain the drug delivery rate for better tumor treatment. Grafting is verified through nuclear magnetic resonance (1H NMR) and other spectroscopic techniques along with the hydrodynamic volume measurement of grafted species and the degree of substitution has been calculated from the integrated peak areas. Thermal and mechanical stability of the graft copolymers have improved significantly with respect to cyclodextrin and the formation of smaller blobs having larger in number has been obtained from small angle neutron scattering, atomic force microscopy and optical images. Sustained drug delivery has been achieved using graft copolymer as opposed to burst release in pure cyclodextrin and polyurethane and the phenomenon is understood from the specific interactions, as observed though spectroscopic and thermal measurement, between graft copolymer and drug followed by this novel architecture of the graft copolymers. Biocompatibility of graft copolymers has been checked using cellular studies through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell adhesion. Importantly, the cell killing efficiency has been demonstrated by embedding anti-cancer drug in polymer matrices causing mortality rate of 80% using graft copolymer against meagre 20% using pure drug or drug embedded in cyclodextrin and the result is realised from the sustained release of drug from the graft copolymer vis-à-vis burst release in other systems. Cellular studies have been translated into an animal model showing the efficacy of newly developed patch, made of drug embedded in copolymer, towards the significant suppression of tumors in mice as compared to control. Histopathological images and biochemical parameters indicate the normal body organ/blood in copolymer treated mice against severely damaged organ especially liver/blood in the mice treated with pure drug or drug embedded in cyclodextrin arising from burst release. Thus, graft copolymer with unique architecture is found to be an effective drug delivery vehicle for melanoma cancer treatment without side effect.
- Molecular reorganization in bulk bottlebrush polymers: direct observation via nanoscale imaging. [Journal Article]
- NNanoscale 2018 Sep 18
- Bottlebrush polymers are important for a variety of applications ranging from drug delivery to electronics. The functional flexibility of the branched sidechains has unique assembly properties when c...
Bottlebrush polymers are important for a variety of applications ranging from drug delivery to electronics. The functional flexibility of the branched sidechains has unique assembly properties when compared to linear block polymer systems. However, reports of direct observation of molecular reorganization have been sparse. This information is necessary to enhance the understanding of the structure-property relationships in these systems and yield a rational design approach for novel polymeric materials. In this work, we report direct visualization of bottlebrush molecular organization and the formation of nematic-type ordering in an amorphous polymer bottlebrush system, captured with plasma etching and helium ion microscopy. By observing the unperturbed structure of this material at high resolution and quantifying image features, we were able to qualitatively link experimental results with structures predicted by coarse-grained molecular dynamics simulations. The direct visualization and computation workflow developed in this work can be applied to a broad variety of polymers with different architectures, linking imaging results with other, independent channels of information for better understanding and control of these classes of materials.
- Static Magnetic Field (SMF) as a Regulator of Stem Cell Fate - New Perspectives in Regenerative Medicine Arising from an Underestimated Tool. [Review]
- SCStem Cell Rev 2018 Sep 17
- Tissue engineering and stem cell-based therapies are one of the most rapidly developing fields in medical sciences. Therefore, much attention has been paid to the development of new drug-delivery sys...
Tissue engineering and stem cell-based therapies are one of the most rapidly developing fields in medical sciences. Therefore, much attention has been paid to the development of new drug-delivery systems characterized by low cytotoxicity, high efficiency and controlled release. One of the possible strategies to achieve these goals is the application of magnetic field and/or magnetic nanoparticles, which have been shown to exert a wide range of effects on cellular metabolism. Static magnetic field (SMF) has been commonly used in medicine as a tool to increase wound healing, bone regeneration and as a component of magnetic resonance technique. However, recent data shed light on deeper mechanism of SMF action on physiological properties of different cell populations, including stem cells. In the present review, we focused on SMF effects on stem cell biology and its possible application as a tool for controlled drug delivery. We also highlighted the perspectives, in which SMF can be used in future therapies in tissue engineering due to its easy application and a wide range of possible effects on cells and organisms.
- The Use of Liquids Ionic Fluids as Pharmaceutically Active Substances Helpful in Combating Nosocomial Infections Induced by Klebsiella Pneumoniae New Delhi Strain, Acinetobacter Baumannii and Enterococcus Species. [Review]
- IJInt J Mol Sci 2018 Sep 15; 19(9)
- This review deals with various microbiological activities of ionic liquids, which constitute the first anti-infective defense against multi-drug-resistant bacteria-with a particular emphasis placed o...
This review deals with various microbiological activities of ionic liquids, which constitute the first anti-infective defense against multi-drug-resistant bacteria-with a particular emphasis placed on medicine and pharmacology. The quoted data on the biological activity of ionic liquids including their antimicrobial properties (depending on the type of a cation or an anion) and are discussed in view of possible applications in nosocomial infections. Dedicated attention is given to finding infections with the Klebsiella pneumoniae New Delhi strain, Acinetobacter baumannii, and Enterococcus species, which are responsible for the induction of antibiotic resistance in intensive care units. Diagnosis and treatment using current antibiotics is a significant problem in hospital care, and the relevant burden on the health systems of the European Union member states induces the search for new, effective methods of treatment. Ionic liquids, due to their antibacterial effect, can be considered topical and general medications and may provide the basis for treatment to eliminate the antibiotic resistance phenomenon in the future. At present, the number of infections with resistant pathogens in hospitals and outpatient clinics in the European Union is growing. In 2015⁻2017, a significant incidence of respiratory and bloodstream infections with bacteria resistant to antibiotics from the 3rd generation group of cephalosporins, glycopeptides, and carbapenems were observed. The paper presents examples of synthesized bifunctional salts with at least one pharmaceutically active ion in obtaining a controlled release, controlled delivery, and biological impact on the pathogenic bacteria, viruses and fungi. The ionic liquids obtained in the presented way may find applications in the treatment of wounds and infections.
- Therapeutic Peptide Amphiphile as a Drug Carrier with ATP-Triggered Release for Synergistic Effect, Improved Therapeutic Index, and Penetration of 3D Cancer Cell Spheroids. [Journal Article]
- IJInt J Mol Sci 2018 Sep 14; 19(9)
- Despite the great progress in the field of drug delivery systems for cancer treatment over the last decade, many challenges still lie ahead, such as low drug loading, deep penetration of tumors, side...
Despite the great progress in the field of drug delivery systems for cancer treatment over the last decade, many challenges still lie ahead, such as low drug loading, deep penetration of tumors, side effects, and the development of drug resistance. A class of cationic membrane lytic peptides has shown potential as an anticancer agent by inducing cancer cell death via membrane disruption; meanwhile, their intrinsic selectivity renders them as having low cytotoxicity towards noncancerous cells. Here, we report the use of a cationic peptide amphiphile (PA), named PAH6, to load doxorubicin (Dox) that is intercalated in an ATP-binding aptamer-incorporated DNA scaffold. The PA contains a cationic lytic sequence, (KLAKLAK)₂, a polyhistidine segment for the "proton sponge" effect, and a hydrophobic alkyl tail to drive the self-assembly. Dox-loaded DNA was found to form a spherical nanocomplex (NC) with PAH6 with particle sizes below 100 nm at various ratios. Since the carrier PAH6 is also a therapeutic agent, the drug loadings of the NC reached up to ~86% within the ratios we tested, and Dox was released from the NC in an ATP-rich environment. In vitro studies indicate that the presence of PAH6 could permeabilize cell membranes and kill cells through fast membrane disruption and depolarization of mitochondrial membranes. The cytotoxicity tests were conducted using A549 nonsmall cell lung cancer cells and NIH-3T3 fibroblast cells. PAH6 showed selectivity towards A549 cells. Significantly, the Dox-DNA/PAH6 NC exhibited a synergistic effect against A549 cells, with the IC50 decreased up to ~90% for Dox and ~69% for PAH6 when compared to the IC50 values of the two components, respectively. Furthermore, the selectivity of PAH6 conferred to the complex an improved therapeutic index between A549 and NIH-3T3 cells. A 3D-cultured A549 spheroid model was adopted to test the capability of Dox-DNA/PAH6 for tumor penetration. The PAH6 or Dox-DNA/PAH6 complex was found to break the spheroids into pieces, while Dox-treated spheroids maintained their shapes. In summary, this work provides a new strategy for constructing nanomedicines using therapeutic agents to meet the features required by anticancer treatment.
- COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer therapy in preclinical models. [Journal Article]
- BBiomaterials 2018 Sep 10; 185:63-72
- Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as an important component in current cancer therapeutic modalities. However, the associated benefits have proven to be mo...
Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as an important component in current cancer therapeutic modalities. However, the associated benefits have proven to be modest as tumor angiogenesis and regrowth persist, probably due to other ill-defined complex angiogenic mechanisms. Herein, we developed an indomethacin (IMC) incorporating system to mediate hypoxia responsive prodrug (TA) and diagnostic agent (DA) in cancer theranostic applications. Cyclooxygenase 2 (COX-2) elevated expression in several cancer types is closely associated with severe tumor supporting vascularization factors. Our strategy utilizing COX-2 inhibition augmented the anti-angiogenetic induced hypoxia responsive prodrug activation well. Both in vitro and in vivo results proved that DA and TA exhibited specificity towards COX-2 positive (+ve) HeLa and A549 cancer cell lines and activation under hypoxic conditions. Compared with controls (R1, and anticancer drug SN-38), TA displayed prolonged tumor retention and enhanced therapeutic efficacy in xenograft mouse models at a reduced dosage. Our results significantly highlighted the importance of COX-2 blockade mediated anti-angiogenesis in complementing the hypoxia-responsive drug delivery systems (DDSs) and could to beneficial for the rapid development of more efficacious antitumor therapeutics.
- Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study. [Journal Article]
- JAJ Am Geriatr Soc 2018 Sep 17
- CONCLUSIONS: Most commonly prescribed nonanticholinergic depression medications used in late life do not appear to be associated with dementia risk. Paroxetine and other anticholinergic antidepressants may be exceptions in older individuals. Future studies are warranted to improve scientific understanding of potential associations in other settings and populations.
- Formulation Development of Self-Nanoemulsifying Drug Delivery System of Celecoxib for the Management of Oral Cavity Inflammation. [Journal Article]
- JLJ Liposome Res 2018 Sep 16; :1-27
- CONCLUSIONS: CLX-SNEDDS was found to achieve effective local therapeutic concentration and intended to reduce cheek edema, congestive capillary, inflammatory cells and reduce side effects due to lower dose size.
- Nanogel Tectonics for Tissue Engineering: Protein Delivery Systems with Nanogel Chaperones. [Review]
- AHAdv Healthc Mater 2018 Sep 16; :e1800729
- Amphiphilic polysaccharide self-assembled (SA) nanogels are promising protein carriers owing to their chaperone-like activity that allows them to nanoencapsulate proteins within their polymer network...
Amphiphilic polysaccharide self-assembled (SA) nanogels are promising protein carriers owing to their chaperone-like activity that allows them to nanoencapsulate proteins within their polymer networks. The chaperoning function is an important concept that has led to breakthroughs in the development of effective protein drug delivery systems by stabilizing formulations and controlling the quality of unstable proteins. Recently, nanogel-tectonic materials that integrate SA nanogels as building blocks have been designed as new hydrogel biomaterials. This article describes recent progress and applications of SA nanogel tectonic materials as protein delivery systems for tissue engineering.
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- A self-targeting and controllable drug delivery system by fabricating with multi-stimuli responsive chitosan-based thin film layer on mesoporous silica nanoparticles. [Journal Article]
- IJInt J Biol Macromol 2018 Sep 13
- Surface modification and functionalization of nanomaterials have been adopted widely in devising smart drug delivery systems. This work examines the fabrication of multi-stimuli responsive surfaces o...
Surface modification and functionalization of nanomaterials have been adopted widely in devising smart drug delivery systems. This work examines the fabrication of multi-stimuli responsive surfaces on mesoporous silica nanoparticles (MSN) for environmentally sensitive site specific drug delivery with reduced risk of premature drug leakage. Chitosan cross-linked via disulfide bonds was applied to form a thin film on drug-loaded MSN, realizing a capsulation and stimuli-sensitive regulating gate membrane; that was further conjugated with folate for site specific targeting toward cancer cells. The chitosan thin film was very stable under neutral conditions and could effectively prevent drug leakage, but was sensitive to both pH and GSH stimulations to reach rapid drug release. Thus, drug release could be triggered by changes in such factors that are common to cancer cells. However, complete and accelerated release could only be realized when triggered simultaneously by both acidic pH and GSH. Moreover, tests with HepG-2 cells confirmed that folate-receptor mediated endocytosis successfully enhanced the cellular uptake of the nanoparticle and antitumor activity toward cancer cells. It is expected that this surface chemical modification strategy promises a powerful approach constructing smart drug delivery systems for efficient and safe chemotherapy.