NDH-4338 is a highly lipophilic prodrug comprising indomethacin and an acetylcholinesterase inhibitor. A design of experiments approach was used to synthesize, characterize, and evaluate the wound healing efficacy of optimized NDH-4338 nanosuspensions against nitrogen mustard-induced skin injury. Nanosuspensions were prepared by sonoprecipitation in the presence of a Vitamin E TPGS aqueous stabilizer solution.
View Article and Find Full Text PDFBackground: Sulfur mustard (SM) is a chemical warfare vesicant that severely injures exposed eyes, lungs, and skin. Mechlorethamine hydrochloride (NM) is widely used as an SM surrogate. This study aimed to develop a depilatory double-disc (DDD) NM skin burn model for investigating vesicant pharmacotherapy countermeasures.
View Article and Find Full Text PDFSulfur mustard (SM; bis(2-chloroethyl) sulfide) is a highly reactive bifunctional alkylating agent synthesized for chemical warfare. The eyes are particularly sensitive to SM where it causes irritation, pain, photophobia, and blepharitis, depending on the dose and duration of exposure. In these studies, we examined the effects of SM vapor on the corneas of New Zealand white male rabbits.
View Article and Find Full Text PDFThe study aims to develop high drug-loaded (about 15% lipid matrix) curcumin solid lipid nanoparticles (CSLNs) for wound healing. CSLNs prepared by hot, high-pressure homogenization, without using organic solvents, were optimized using the Taguchi design followed by the central composite design. The optimized CSLNs exhibited a high assay/drug content (0.
View Article and Find Full Text PDFDuctal carcinoma in situ (DCIS) represents approximately 20-25% of newly diagnosed breast cancers. DCIS is treated by surgery and possibly radiotherapy. Chemotherapy is only used as adjuvant or neoadjuvant therapy but not as primary therapy.
View Article and Find Full Text PDFNanocarriers (NCs) are an attractive class of vehicles for drug delivery with the potential to improve drug efficacy and safety, particularly for intravenous parenteral delivery. Many therapeutics remain challenging to formulate in NCs due to their intrinsic solubilities that frustrate NC loading or result in too rapid release . Therapeutic conjugate approaches that alter the solubility of a conjugate "prodrug" have been used to enable NC formation and controlled release from NCs using labile linker chemistry.
View Article and Find Full Text PDFSulfur mustard (SM), a dermal vesicant that has been used in chemical warfare, causes inflammation, edema and epidermal erosions depending on the dose and time following exposure. Herein, a minipig model was used to characterize wound healing following dermal exposure to SM. Saturated SM vapor caps were placed on the dorsal flanks of 3-month-old male Gottingen minipigs for 30 min.
View Article and Find Full Text PDFIntroduction: Ductal Carcinoma In Situ (DCIS) represents a significant fraction (~20-25%) of all newly diagnosed breast cancer cases and, if left untreated, a significant fraction of patients will progress to invasive disease. Surgery is the only treatment option. Ciclopirox (CPX), an FDA-approved antifungal drug, has exhibited promising antitumor activity by down-regulating the expression of vital antiapoptotic cellular proteins and inhibiting the genetic expression of several oncogenic pathways.
View Article and Find Full Text PDFPersistent activation of macrophages (MP)s into a proinflammatory M1 or anti-inflammatory M2 phenotype plays a role in several pathological conditions, including autoimmune diseases, fibrosis, infections, atherosclerosis and tumor development. The mannose receptor (MR, CD206), expressed at low levels on resting MPs and absent on M1 MPs, is highly expressed on M2 MPs, making it a potential target and drug delivery portal. Recently, we developed a novel, highly selective MR targeting ligand (MRTL), consisting of two mannose molecules separated by a monodisperse 12 unit poly(ethylene glycol) linker, to enhance the cellular uptake of polymeric nanocarriers.
View Article and Find Full Text PDFDuctal carcinoma in situ is the most commonly diagnosed early stage breast cancer. The efficacy of intraductally delivered poly(ethylene glycol)-doxorubicin (PEG-DOX) nanocarriers, composed of one or more DOX conjugated to various PEG polymers, was investigated in an orthotopic ductal carcinoma in situ-like rat model. In vitro cytotoxicity was evaluated against 13762 Mat B III cells using MTT assay.
View Article and Find Full Text PDFThe feasibility of utilizing the cell surface chemokine receptor CXCR4 for human immunodeficiency virus (HIV) entry inhibition and as an intracellular portal for targeted drug delivery was evaluated. Novel DV3 ligands (1DV3, 2DV3, and 4DV3) were designed, synthesized and conjugated to various probes (fluorescein isothiocyanate (FITC) or biotin) and cargos with sizes ranging from 10 to 50 nm (polyethylene glycol (PEG), streptavidin, and a polymeric nanoparticle). 4DV3 conjugated probes inhibited HIV-1 entry into the CXCR4-expressing reporter cell line TZM-bl (IC at 553 nM) whereas 1DV3 and 2DV3 did not.
View Article and Find Full Text PDFAlthough systemic administration of chemotherapeutic agents is routinely used for treating invasive breast cancer, the only therapeutic options for ductal carcinoma in situ (DCIS) are surgery and radiation. Treating DCIS by delivering drugs locally to the affected milk duct offers significant advantages over systemic administration, including reduced systemic and breast toxicities, as well as a greatly reduced need for surgery and radiation. In this study, mammary gland retention and toxicity of intraductally administered poly(ethylene) glycol-doxorubicin (PEG-DOX) polymeric conjugate nanocarriers of varying molecular sizes and architectures were investigated.
View Article and Find Full Text PDFMol Ther Nucleic Acids
April 2016
The development of a convenient and sensitive biosensing system to detect specific DNA sequences is an important issue in the field of genetic disease therapy. As a classic DNA detection technique, molecular beacon (MB) is often used in the biosensing system. However, it has intrinsic drawbacks, including high assay cost, complicated chemical modification, and operational complexity.
View Article and Find Full Text PDFThe circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay.
View Article and Find Full Text PDFLocal delivery of anti-HIV drugs to the colorectal mucosa, a major site of HIV replication, and their retention within mucosal tissue would allow for a reduction in dose administered, reduced dosing frequency and minimal systemic exposure. The current report describes a mucosal pre-exposure prophylaxis (mPrEP) strategy that utilizes nanocarrier conjugates (NC) consisting of poly(ethylene glycol) (PEG), amprenavir (APV), and a cell-penetrating peptide (CPP; namely Bac7, a fragment derived from bactenecin 7). APV-PEG NCs with linear PEGs (2, 5, 10, and 30 kDa) exhibited reduced (52-21%) anti-HIV-1 protease (PR) activity as compared to free APV in an enzyme-based FRET assay.
View Article and Find Full Text PDFUSA and China are two leading countries engaged in nanotechnology research and development. They compete with each other for fruits in this innovative area in a parallel and compatible manner. Understanding the status and developmental prospects of nanotechnology in USA and China is important for policy-makers to decide nanotechnology priorities and funding, and to explore new ways for global cooperation on key issues.
View Article and Find Full Text PDFThe year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today.
View Article and Find Full Text PDFWe have developed responsive foam systems for nanoparticle delivery. The foams are easy to make, stable at room temperature, and can be engineered to break in response to temperature or moisture. Temperature-responsive foams are based on the phase transition of long chain alcohols and could be produced using medical grade nitrous oxide as a propellant.
View Article and Find Full Text PDFBackground: This study was aimed at establishing a sensitive and specific isolation, characterization, and enumeration method for living circulating tumor cells (CTCs) in patients with colorectal carcinoma.
Methods: Quantitative isolation and characterization of CTCs were performed through a combination of immunomagnetic negative enrichment and fluorescence-activated cell sorting. Isolated CTCs were identified by immunofluorescence staining.
Circulating tumor cells (CTCs) have been detected by us and others in cancer patient blood. However, little is known about how to specifically capture and deactivate CTCs in vivo, which may lead to successful metastasis prevention in asymptomatic cancer survivors after surgery. We hypothesize that the dual antibody conjugates may have the advantage of capturing CTCs specifically over their single antibody counterparts.
View Article and Find Full Text PDFMagnetic resonance imaging (MRI)- and near-infrared (NIR)-active, multimodal composite nanocarriers (CNCs) are prepared using a simple one-step process, flash nanoprecipitation (FNP). The FNP process allows for the independent control of the hydrodynamic diameter, co-core excipient and NIR dye loading, and iron oxide-based nanocrystal (IONC) content of the CNCs. In the controlled precipitation process, 10 nm IONCs are encapsulated into poly(ethylene glycol) (PEG) stabilized CNCs to make biocompatible T2 contrast agents.
View Article and Find Full Text PDFCirculation tumor cells (CTCs) in the bloodstream of early-stage cancer patients carry the important information about valuable biomarkers and biological properties of primary tumor. However, detection and capture of CTCs are challenging owing to their low concentrations. Traditional technologies have the limited detection sensitivity and the low capture efficiency.
View Article and Find Full Text PDFTuberculosis (TB) remains a major global health concern, and new therapies are needed to overcome the problems associated with dosing frequency, patient compliance, and drug resistance. To reduce side effects associated with systemic drug distribution and improve drug concentration at the target site, stable therapeutic nanocarriers (NCs) were prepared and evaluated for efficacy in vitro in Mycobacterium tuberculosis-infected macrophages. Rifampicin (RIF), a current, broad-spectrum antibiotic used in TB therapy, was conjugated by degradable ester bonds to form hydrophobic prodrugs.
View Article and Find Full Text PDFBackground: Cancer metastasis caused by circulating tumor cells (CTCs) accounts for 90% cancer-related death worldwide. Blocking the circulation of CTCs in bloodstream and their hetero-adhesion to vascular endothelia of the distant metastatic organs may prevent cancer metastasis. Nanomaterial-based intervention with adhesion between CTCs and endothelia has not been reported.
View Article and Find Full Text PDFMifepristone (RU486), a synthetic steroid compound used as an abortifacient drug, has received considerable attention to its anticancer activity recently. To explore the possibility of using mifepristone as a cancer metastasis chemopreventive, we performed a systems pharmacology analysis of mifepristone-related molecules in the present study. Data were collected by using Natural Language Processing (NLP) and 513 mifepristone-related genes were dug out and classified functionally using a gene ontology (GO) hierarchy, followed by KEGG pathway enrichment analysis.
View Article and Find Full Text PDF