Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged time, reduce the overall drug dose needed, and suppress severe side effects. Herein, nanofibrous carriers of the anticancer agent topotecan (TPT) with a multilayered structure composed of a TPT-loaded inner layer of poly(vinyl alcohol) (PVA) and outer covering layers of polyurethane (PUR) are proposed. Scanning electron microscopy showed homogeneous incorporation of TPT into the PVA nanofibers. HPLC-FLD proved the good loading efficiency of TPT (≥85%) with a content of the pharmacologically active lactone TPT of more than 97%. In vitro release experiments demonstrated that the PUR cover layers effectively reduced the initial burst release of hydrophilic TPT. In a 3-round experiment with human retinoblastoma cells (Y-79), TPT showed prolonged release from the sandwich-structured nanofibers compared with that from a PVA monolayer, with significantly enhanced cytotoxic effects as a result of an increase in the PUR layer thickness. The presented PUR-PVA/TPT-PUR nanofibers appear to be promising carriers of active TPT lactone that could be useful for local cancer therapy.
- Publikační typ
- časopisecké články MeSH
Transscleral diffusion delivery of chemotherapy is a promising way to reach the vitreal seeds of retinoblastoma, the most common intraocular malignancy in childhood. In this in vivo study, the delivery of topotecan via lens-shaped, bi-layered hydrogel implants was combined with transconjunctival cryotherapy to assess whether cryotherapy leads to higher concentrations of topotecan in the vitreous. The study included 18 New Zealand albino rabbits; nine rabbits received a topotecan-loaded implant episclerally and another nine rabbits received transconjunctival cryotherapy superotemporally 2 weeks before implant administration. Median vitreous total topotecan exposures (area under the curve, AUC) were 455 ng·h/mL for the cryotherapy group and 281 ng·h/mL for the non-cryotherapy group, and were significantly higher in the cryotherapy group, similar to maximum levels. Median plasma AUC were 50 ng·h/mL and 34 ng·h/mL for the cryotherapy and non-cryotherapy groups, respectively, with no statistically significant differences between them. In both groups, AUC values in the vitreous were significantly higher than in plasma, with plasma exposure at only approximately 11-12% of the level of vitreous exposure. The results confirmed the important role of the choroidal vessels in the pharmacokinetics of topotecan during transscleral administration and showed a positive effect of cryotherapy on intravitreal penetration, resulting in a significantly higher total exposure in the vitreous.
- Publikační typ
- časopisecké články MeSH
Treatment of retinoblastoma (Rb) has greatly improved in recent years in terms of survival and eye salvage rates, using mainly intra-arterial or intravitreal chemotherapy. However, the treatment of vitreous tumor seeding still represents a challenge and it is of great interest to develop new strategies to deliver pharmacologically sufficient drug amounts to the vitreous humor. In the present work, we present a lens-shaped bi-layered hydrogel implant for delivery of topotecan (TPT) via transscleral diffusion. The implant consists of an inner TPT-loaded poly(2-hydroxyethyl methacrylate) (pHEMA) layer adjacent to the sclera and an outer covering poly(2-ethoxyethyl methacrylate) (pEOEMA) layer impermeable to TPT. TPT-loaded pHEMA samples exhibit long-lasting in vitro cytotoxicity against the Rb cell line Y79. In an in vivo experiment, pHEMA/pEOEMA implants are successfully surgically administered to the posterior segment of rabbit eyes. The determination of TPT pharmacokinetics demonstrates the attainment of promising levels of TPT (10 ng/ml) in vitreous humor 8 h after implant placement. The results from the pilot experiment constitute the proof of principle for the use of the proposed implants as a drug delivery system for the local treatment of intraocular diseases.
- Publikační typ
- abstrakt z konference MeSH
Chronic wounds and their associated bacterial infections are major issues in modern health care systems. Therefore, antimicrobial resistance (AMR), treatment costs, and number of disability-adjusted life-years have gained more interest. Recently, photodynamic therapy emerged as an effective approach against resistant and naïve bacterial strains with a low probability of creating AMR. In this study, needleless electrospinning was used to produce an indocyanine green (ICG) loaded poly(d,l-lactide) nanofibrous mesh as a photoresponsive wound dressing. The non-woven mesh had a homogeneous nanofibrous structure and showed long-term hydrolytic stability at different pH values. The antimicrobial activity was tested against several bacterial strains, namely Staphylococcus saprophyticus subsp. bovis, Escherichia coli DH5 alpha, and Staphylococcus aureus subsp. aureus. Upon irradiation with a laser of a specific wavelength (λ = 810 nm), the bacterial viability was significantly reduced by 99.978% (3.66 log10), 99.699% (2.52 log10), and 99.977% (3.64 log10), respectively. The nanofibrous mesh showed good biocompatibility, which was confirmed by the proliferation of mouse fibroblasts (L929) on the surface and into deeper parts of the mesh. Furthermore, a favorable proangiogenic effect was observed in ovo using the chorioallantoic membrane assay. In general, it can be concluded that ICG loaded nanofibers as an innovative wound dressing represent a promising strategy against chronic wounds associated with skin infections.
- MeSH
- biokompatibilní materiály chemie farmakologie MeSH
- buněčné linie MeSH
- chorioalantoická membrána krevní zásobení účinky léků MeSH
- Escherichia coli účinky léků růst a vývoj MeSH
- fibroblasty cytologie účinky léků MeSH
- fotochemoterapie MeSH
- indokyanová zeleň chemie farmakologie MeSH
- mikrobiální viabilita účinky léků MeSH
- myši MeSH
- nanovlákna MeSH
- obvazy MeSH
- polyestery chemie MeSH
- proliferace buněk účinky léků MeSH
- Staphylococcus aureus účinky léků růst a vývoj MeSH
- Staphylococcus saprophyticus účinky léků růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Retinoblastoma (Rb) is the most common primary malignant intraocular tumor in children which develops from the retinal stem cells. Systemic chemotherapy is the typical therapeutic treatment and though most children survive Rb, they often lose their vision, or the eye needs to be enucleated. Regarding to the pure availability of the target tumor by systemic chemotherapy, the local anticancer drug administration would be advantageous to increase the local drug concentration and minimize adverse side effects of chemotherapy. The present paper describes a new hydrogel implant enabled to deliver therapeutically active doses of low molecular weight hydrophilic antitumor drugs topotecan and vincristine. The hydrogel implant is proposed as bi-layered with an inner hydrophilic layer from 2-hydroxyethyl methacrylate (HEMA) serving as a reservoir of the chemotherapeutic agent and an outer hydrophobic layer from 2-ethoxyethyl methacrylate (EOEMA) acting as a barrier to protect the surrounding vascularized tissue against cytotoxicity of the delivered chemotherapeutics. The experiments with enucleated pig eyes demonstrated the ability of tested drugs to diffuse through sclera and reach the vitreous humor. HEMA-based hydrogels were examined in terms of sorption, release and transport properties, showing the possibility of adjusting the loading capacity and diffusion of the drugs by the degree of crosslinking. The EOEMA-based gels proved to be an inert for drug sorption and diffusion. A chorioallantoic membrane assay demonstrated excellent biocompatibility of unloaded hydrogels, and in vitro experiments confirmed significant cytotoxicity of drug-loaded hydrogels against a Rb cell line; 2 days for those topotecan-loaded and a minimum of 6 days for vincristine-loaded hydrogels. The bi-layered hydrogel implant can be considered promising for local administration of active agents to eye-globe for the treatment of Rb and also other ocular disorders.
- MeSH
- hydrogely chemie MeSH
- kinetika MeSH
- lidé MeSH
- methakryláty chemie MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemie MeSH
- oči účinky léků metabolismus MeSH
- prasata MeSH
- protézy a implantáty MeSH
- retinoblastom metabolismus patologie MeSH
- stabilita léku MeSH
- topotekan chemie metabolismus farmakologie MeSH
- viabilita buněk účinky léků MeSH
- vinkristin chemie metabolismus farmakologie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cancer despite the introduction of new targeted therapy remains for many patients a fatal disease. Nanotechnology in cancer medicine has emerged as a promising approach to defeat cancer. Targeted delivery of anti-cancer drugs by different nanosystems promises enhanced drug efficacy, selectivity, better safety profile and reduced systemic toxicity. The article presents an overview of recent developments in cancer nanomedicine. We focus on approved anti-cancer medical products and on the results of clinical studies, highlighting that liposomal and micellar cytostatics or albumin-based nanoparticles have less side effects and are more efficient than "free" drugs. In addition, we discuss results of in vitro and in vivo preclinical studies with lipid, inorganic and polymer nanosystems loaded by anticancer drugs which according to our meaning are important for development of new nanodrugs. Pharmacokinetic characteristics of nanodrugs are discussed and characterization of major nanotechnology systems used for cancer nanomedicine is presented.
- MeSH
- albuminy MeSH
- antitumorózní látky aplikace a dávkování MeSH
- lidé MeSH
- liposomy MeSH
- micely MeSH
- nádory farmakoterapie MeSH
- nanotechnologie * MeSH
- systémy cílené aplikace léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.
- MeSH
- buněčná smrt účinky léků MeSH
- difrakce rentgenového záření MeSH
- inhibitory angiogeneze farmakologie MeSH
- kur domácí MeSH
- lidé MeSH
- lokální recidiva nádoru patologie prevence a kontrola MeSH
- myši nahé MeSH
- nádorové buněčné linie MeSH
- nanovlákna chemie ultrastruktura MeSH
- nosiče léků chemie MeSH
- paclitaxel farmakologie MeSH
- polyestery chemie MeSH
- polyethylenglykoly chemie MeSH
- tělesná hmotnost MeSH
- teplota MeSH
- tumor burden účinky léků MeSH
- uvolňování léčiv * MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Currently, chemotherapy is the most common treatment for oncological diseases. Systemic administration of chemotherapeutics provides an easy and effective distribution of the active agents throughout the patient's body, however organs may be severely impaired by serious life-threatening side effects. In many oncological diseases, particularly solid tumors, the local application of chemotherapeutics would be advantageous. Recently, nanofibrous materials as local drug delivery systems have attracted much attention. They have considerable potential in the treatment of various cancers as they can provide a high concentration of the drug at the target site for a prolonged time, thereby lowering total exposure and adverse effects. The present review describes the specifics of drug delivery to the tumor microenvironment, basic characteristics of nanofibrous materials and their preparation, and comprehensively summarizes recent scientific reports concerning in vivo experiments with drug-loaded electrospun nanofibrous systems designed for local anticancer therapy.
Polymeric bile acid sequestrants (BAS) have recently attracted much attention as lipid-lowering agents. These non-absorbable materials specifically bind bile acids (BAs) in the intestine, preventing bile acid (BA) reabsorption into the blood through enterohepatic circulation. Therefore, it is important to understand the structure-property relationships between the polymer sequestrant and its ability to bind specific BAs molecules. In this review, we describe pleiotropic effects of bile acids, and we focus on BAS with various molecular architectures that result in different mechanisms of BA sequestration. Here, we present 1) amphiphilic polymers based on poly(meth)acrylates, poly(meth)acrylamides, polyalkylamines and polyallylamines containing quaternary ammonium groups, 2) cyclodextrins, and 3) BAS prepared via molecular imprinting methods. The synthetic approaches leading to individual BAS preparation, as well as results of their in vitro BA binding activities and in vivo lipid-lowering activities, are discussed.
- MeSH
- anticholesteremika chemická syntéza chemie farmakologie MeSH
- hypercholesterolemie farmakoterapie MeSH
- lidé MeSH
- molekulární struktura MeSH
- polymery chemická syntéza chemie farmakologie MeSH
- racionální návrh léčiv * MeSH
- vazebná místa účinky léků MeSH
- žlučové kyseliny a soli chemická syntéza chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
