•CNTs are considered as superior adsorbent for adsorption of guest molecules.•Functionalization is a well-known approach for alteration of the surface.•Purification is a prime factor in ...CNTs.•Conjugation of PEG to nanobiomaterials is known as PEGylation.•Stimuli-responsive engineered CNTs may offer interesting opportunities in targeting.
Applications of carbon nanotubes (CNTs) in the biomedical arena have gained increased attention over the past decade. Surface engineering of CNTs by covalent and noncovalent modifications enables site-specific drug delivery and targeting. CNTs are available as single-, double-, triple-, and multiwalled carbon nanotubes (SWCNTs, DWCNTs, TWCNTs, and MWCNTs, respectively) and have unique physicochemical properties, including a high surface area, high loading efficiency, good biocompatibility, low toxicity, ultra lightweight, rich surface chemistry, non-immunogenicity, and photoluminescence. In this review, we highlight current understanding of the different types of physical and chemical interaction that occur between therapeutics and CNTs, and the potential application of the latter in drug delivery and imaging. Such understanding will aid exploration of the utility of multifunctional CNTs as pharmaceutical nanocarriers, and potential safety and toxicity issues.
The present review provides a novel platform to scientist for CNTs and their conjugation chemistry, interactions, conjugation, and their potential biological applications in drug delivery perspectives.
Many synthetic drugs and monoclonal antibodies are currently in use to treat Inflammatory Bowel Disease (IBD). However, they all are implicated in causing severe side effects and long-term use ...results in many complications. Numerous in vitro and in vivo experiments demonstrate that phytochemicals and natural macromolecules from plants and animals reduce IBD-related complications with encouraging results. Additionally, many of them modify enzymatic activity, alleviate oxidative stress, and downregulate pro-inflammatory transcriptional factors and cytokine secretion. Translational significance of natural nanomedicine and strategies to investigate future natural product-based nanomedicine is discussed. Our focus in this review is to summarize the use of phytochemicals and macromolecules encapsulated in nanoparticles for the treatment of IBD and IBD-associated colorectal cancer.
Controlled delivery of a bioactive to specific organ, cellular and sub-cellular level is a desired feature of a drug carrier system. In order to achieve this goal, formulation scientists search for ...better alternatives of biomaterials to deliver the therapeutics in more precise and controlled manner in vivo. Zein, a plant protein obtained from corn, is a useful biomaterial for several industrial applications including agriculture, cosmetics, packaging and pharmaceuticals. Being a hydrophobic protein, which is biodegradable, biocompatible, economic to use and with generally regarded safe "GRAS" status, it is an attractive biomaterial for human use. Novel biomedical applications of zein such as controlled and targeted delivery of bioactives and tissue engineering are the current research interests of the scientific fraternity. Here we attempt to review the literature on zein as a biopolymer for drug/vaccine/gene delivery and its applicability in tissue engineering.
Multifunctional nanomaterials are rapidly emerging for ophthalmic delivery of therapeutics to facilitate safe and effective targeting with improved patient compliance. Because of their extremely high ...area to volume ratio, nanomaterials often have physicochemical properties that are different from those of their larger counterparts. There exists a complex relationship between the physicochemical properties (composition, size, shape, charge, roughness, and porosity) of the nanomaterials and their interaction with the biological system. The eye is a very sensitive accessible organ and is subjected to intended and unintended exposure to nanomaterials. Currently, various ophthalmic formulations are available in the market, while some are underway in preclinical and clinical phases. However, the data on safety, efficacy, and toxicology of these advanced nanomaterials for ocular drug delivery are sparse. Focus of the present review is to provide a comprehensive report on the safety, biocompatibility and toxicities of nanomaterials in the eye.
Clinical use of SN38 is limited by its poor aqueous solubility and hydrolysis of the lactone ring at pH > 6 to inactive carboxylate form. A variety of drug delivery systems have been developed to ...improve the solubility and stability of SN38, and reduce its toxicity. A few noteworthy formulations with some success in initial phases of clinical trials are reported.
This work aims to provide a comprehensive review on the various techniques and strategies employed (physical, chemical and biological methods) to improve physicochemical properties and to deliver the drug efficiently to the cancer cells. Physical methods such as nanoparticle encapsulation, cyclodextrin complexation; chemical methods such as prodrugs, polymer-, albumin- and immunoconjugates; and enzyme activated prodrug therapy are discussed.
The challenges in SN38 drug delivery may be overcome by two ways: ensuring multiple layers of protection against degradation and slow but sustained release of therapeutically effective drug concentrations. It may also be achieved by preparing a polymer-drug conjugate and further encapsulating the conjugate in suitable carrier system; tumor-targeted SN38 delivery by using immunoconjugates, enzyme-activated prodrug therapy and antibody-directed nanoparticle delivery. However, selection of a suitable ligand for tumor targeting and use of safe and biocompatible nanoparticle systems play an important role in realizing this goal.
Biotin is an essential micronutrient and its levels are high in rapidly proliferating cells such as cancer cells. We hypothesized that the synthesis of poly (amido)amine (PAMAM) dendrimers with ...biotin molecules might contribute to enhanced cancer cell-specific uptake.
PAMAM dendrimers were biotinylated using sulfo-NHS-LC-biotin and structural characterization was performed using 1H NMR and matrix assisted laser desorption ionization--time-of-flight. The effect of generation and the mechanism of cellular uptake of biotin-PAMAMG4 in ovarian cancer (OVCAR-3) and human embryonic kidney (HEK 293T) cells was determined by fluorescent microscopy and flow cytometry.
The cellular uptake of Biotin-PAMAM was significantly higher in the OVCAR-3 cells as compared to the HEK 293T cells (p<0.05). While the presence of either free biotin or colchicine significantly reduced the extent of uptake of biotin-PAMAMG4 at lower concentration (0.1 microM). The results demonstrated that the biotinylated-PAMAM was internalized by biotin receptor-mediated endocytosis and charge-mediated adsorptive endocytosis. The cytotoxicity of biotinylated-PAMAMG4 in the HEK 293T cells was comparable to that of the parent PAMAM dendrimers.
Biotinylated PAMAM dendrimers show potential as nanocarriers in targeted drug delivery.
Endometrial cancer (EC) often exhibit aberrant activation of PI3K/Akt/mTOR signaling and targeted therapies using mTOR inhibitors showed limited success. The epigenetic modifier, lysine-specific ...histone demethylase-1A (KDM1A/LSD1) is overexpressed in EC, however, the mechanistic and therapeutic implications of KDM1A in EC are poorly understood. Here, using 119 FDA-approved drugs screen, we identified that KDM1A inhibition is highly synergistic with mTOR inhibitors. Combination therapy of KDM1A and mTOR inhibitors potently reduced the cell viability, survival, and migration of EC cells. Mechanistic studies demonstrated that KDM1A inhibition attenuated the activation of mTOR signaling cascade and abolished rapamycin induced feedback activation of Akt. RNA-seq analysis identified that KDM1A inhibition downregulated the expression of genes involved in rapamycin induced activation of Akt, including the mTORC2 complex. Chromatin immunoprecipitation experiments confirmed KDM1A recruitment to the promoter regions of mTORC2 complex genes and that KDM1A inhibition promoted enrichment of repressive H3K9me2 marks at their promoters. Combination therapy of KDM1A inhibitor and rapamycin reduced the tumor growth in EC xenograft and patient derived xenograft models in vivo and patient derived tumor explants ex vivo. Importantly, in silico analysis of TCGA EC patients data sets revealed that KDM1A expression positively correlated with the levels of PI3K/Akt/mTOR genes. Collectively, our results provide compelling evidence that KDM1A inhibition potentiates the activity of mTOR inhibitors by attenuating the feedback activation of Akt survival signaling. Furthermore, the use of concurrent KDM1A and mTOR inhibitors may be an attractive targeted therapy for EC patients.
•From the drug screen, we found that KDM1A inhibition is highly synergistic with mTOR inhibitors.•KDM1A inhibition attenuated the mTOR signaling cascade and abolished rapamycin induced feedback activation of Akt.•KDM1A is recruited to the promoters of mTORC2 complex genes and KDM1A inhibition caused enrichment of repressive histone methyl marks to reduce their expression.•KDM1A inhibitor and rapamycin combination reduced the tumor growth in primary patient derived explant (PDEX), EC xenograft, and PDX models.
A sensitive and selective RP‐HPLC method has been developed and validated for the quantification of a highly potent poly ADP ribose polymerase inhibitor talazoparib (TZP) in rat plasma. ...Chromatographic separation was performed with isocratic elution method. Absorbance for TZP was measured with a UV detector (SPD‐20A UV–vis) at a λmax of 227 nm. Protein precipitation was used to extract the drug from plasma samples using methanol–acetonitrile (65:35) as the precipitating solvent. The method proved to be sensitive and reproducible over a 100–2000 ng/mL linearity range with a lower limit of quantification (LLQC) of 100 ng/mL. TZP recovery was found to be >85%. Following analytical method development and validation, it was successfully employed to determine the plasma protein binding of TZP. TZP has a high level of protein binding in rat plasma (95.76 ± 0.38%) as determined by dialysis method.
The unique properties of poly(amido)amine dendrimers such as nano size, multifunctional surface, ability to encapsulate and bind the guest molecules, efficient membrane transport and shelf-life ...stability have made them a promising carrier in drug delivery. The two key applications of dendrimers include increasing the solubility and sustained release of molecules, and drug targeting by grafting the cell-specific ligands on the surface. Despite their potential in drug delivery, inherent cytotoxicity, reticuloendothelial system uptake and hemolysis limit their use in clinical applications. Research groups have been working on surface modification methods to mitigate these problems. Herein we present a brief discussion on current surface modification approaches to: i) increase targeting efficiency; ii) increase the cellular permeability for enhanced absorption; iii) increase gene transfection efficiency; and iv) decrease the toxicity of the dendrimers, with a few classic examples. As the knowledge of relationship between the dendrimer surface chemistry and its mode of interactions with cell membrane is developed, so do the modifications of dendrimer structure to render them nontoxic, biocompatible, biodegradable and improve their pharmacodynamic and pharmacokinetic properties. Development of multifunctional dendrimers with each functional unit imparting a distinct characteristic feature such as target cell recognition, enhanced cellular transport, reduction in reticuloendothelial system uptake and stability in in vivo environment holds a great potential for future biomedical applications.
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