Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.
- MeSH
- akrylové pryskyřice * chemie MeSH
- diferenciální skenovací kalorimetrie MeSH
- difrakce rentgenového záření MeSH
- hydrogely * chemie MeSH
- koncentrace vodíkových iontů MeSH
- králíci MeSH
- lékové transportní systémy MeSH
- léky s prodlouženým účinkem chemie farmakokinetika MeSH
- mikroskopie elektronová rastrovací MeSH
- nosiče léků chemie MeSH
- poloxamer * chemie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- termogravimetrie MeSH
- timolol * aplikace a dávkování farmakokinetika chemie MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.
- MeSH
- chitosan * chemie MeSH
- doxorubicin chemie MeSH
- jodacetamid MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- monoklonální protilátky chemie MeSH
- nádory prsu * farmakoterapie MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- trastuzumab MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.
- MeSH
- akrylamidy chemie farmakologie aplikace a dávkování MeSH
- antiflogistika farmakologie aplikace a dávkování chemie MeSH
- Aspirin * aplikace a dávkování farmakologie chemie MeSH
- cyklooxygenasy metabolismus MeSH
- inhibitory cyklooxygenasy farmakologie aplikace a dávkování chemie MeSH
- léky s prodlouženým účinkem * MeSH
- mediátory zánětu metabolismus MeSH
- myši MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- polymery * chemie aplikace a dávkování MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Restoring the structures and functions of tissues along with organs in human bodies is a topic gathering attention nowadays. These issues are widely discussed in the context of regenerative medicine. Excipients/delivery systems play a key role in this topic, guaranteeing a positive impact on the effectiveness of the drugs or therapeutic substances supplied. Advances in materials engineering, particularly in the development of hydrogel biomaterials, have influenced the idea of creating an innovative material that could serve as a carrier for active substances while ensuring biocompatibility and meeting all the stringent requirements imposed on medical materials. This work presents the preparation of a natural polymeric material based on pullulan modified with silymarin, which belongs to the group of flavonoids and derives from a plant called Silybum marianum. Under UV light, matrices with a previously prepared composition were crosslinked. Before proceeding to the next stage of the research, the purity of the composition of the matrices was checked using Fourier-transform infrared (FT-IR) spectroscopy. Incubation tests lasting 19 days were carried out using incubation fluids such as simulated body fluid (SBF), Ringer's solution, and artificial saliva. Changes in pH, electrolytic conductivity, and weight were observed and then used to determine the sorption capacity. During incubation, SBF proved to be the most stable fluid, with a pH level of 7.6-7.8. Sorption tests showed a high sorption capacity of samples incubated in both Ringer's solution and artificial saliva (approximately 350%) and SBF (approximately 300%). After incubation, the surface morphology was analyzed using an optical microscope for samples demonstrating the greatest changes over time. The active substance, silymarin, was released using a water bath, and then the antioxidant capacity was determined using the Folin-Ciocâlteu test. The tests carried out proved that the material produced is active and harmless, which was shown by the incubation analysis. The continuous release of the active ingredient increases the biological value of the biomaterial. The material requires further research, including a more detailed assessment of its balance; however, it demonstrates promising potential for further experiments.
- MeSH
- glukany * chemie MeSH
- koncentrace vodíkových iontů MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- nosiče léků * chemie MeSH
- polyethylenglykoly * chemie MeSH
- silymarin * chemie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ABC transportéry MeSH
- cytostatické látky aplikace a dávkování terapeutické užití MeSH
- doxorubicin aplikace a dávkování terapeutické užití MeSH
- geny MDR MeSH
- inhibitory HIV-proteasy farmakologie terapeutické užití MeSH
- inhibitory proteas farmakologie terapeutické užití MeSH
- lidé MeSH
- Lopinavir aplikace a dávkování terapeutické užití MeSH
- mnohočetná léková rezistence * účinky léků MeSH
- nádory farmakoterapie MeSH
- nanočásticový lékový transportní systém MeSH
- P-glykoprotein metabolismus účinky léků MeSH
- protinádorové látky aplikace a dávkování terapeutické užití MeSH
- transkripční faktor STAT3 metabolismus MeSH
- Check Tag
- lidé MeSH
Lipid nanoparticle (LNP)-mRNA complexes are transforming medicine. However, the medical applications of LNPs are limited by their low endosomal disruption rates, high toxicity and long tissue persistence times. LNPs that rapidly hydrolyse in endosomes (RD-LNPs) could solve the problems limiting LNP-based therapeutics and dramatically expand their applications but have been challenging to synthesize. Here we present an acid-degradable linker termed 'azido-acetal' that hydrolyses in endosomes within minutes and enables the production of RD-LNPs. Acid-degradable lipids composed of polyethylene glycol lipids, anionic lipids and cationic lipids were synthesized with the azido-acetal linker and used to generate RD-LNPs, which significantly improved the performance of LNP-mRNA complexes in vitro and in vivo. Collectively, RD-LNPs delivered mRNA more efficiently to the liver, lung, spleen and brains of mice and to haematopoietic stem and progenitor cells in vitro than conventional LNPs. These experiments demonstrate that engineering LNP hydrolysis rates in vivo has great potential for expanding the medical applications of LNPs.
- Klíčová slova
- nanoterapeutika,
- MeSH
- imunoterapie metody MeSH
- nádory * farmakoterapie MeSH
- nanočásticový lékový transportní systém * MeSH
- objevování léků MeSH
- Publikační typ
- novinové články MeSH
- rozhovory MeSH
Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters. Efficient surface modification of liposomes was confirmed by transmission electron microscopy, atomic force microscopy, and gradient ultracentrifugation. The ability of long-term circulation in the vascular bed was demonstrated in rabbits after i.v. application of fluorescently labelled liposomes. Compared to PEGylated liposomes, HPMA-based copolymer-modified liposomes did not induce specific antibody formation and did not activate murine and human complement. Compared with PEGylated liposomes, HPMA-based copolymer-modified liposomes showed a better long-circulating effect after repeated administration. HPMA-based copolymer-modified liposomes thus represent suitable new candidates for a generation of safer and improved liposomal drug delivery platforms.
- MeSH
- akrylamidy chemie MeSH
- aktivace komplementu účinky léků MeSH
- cholesterol chemie krev MeSH
- hydrofobní a hydrofilní interakce * MeSH
- králíci MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- liposomy * MeSH
- myši MeSH
- polyethylenglykoly * chemie MeSH
- polymery chemie MeSH
- povrchové vlastnosti * MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Polysaccharides like hyaluronan (HA) and chondroitin sulfate (CS) are native of the brain's extracellular matrix crucial for myelination and brain maturation. Despite extensive research on HA and CS as drug delivery systems (DDS), their high water solubility limits their application as drug carriers. This study introduces an injectable DDS using aldehyde-modified hyaluronic acid (HAOX) hydrogel containing polyelectrolyte complexes (PEC) formed with calcium, gelatin, and either CS or aldehyde-modified CS (CSOX) to deliver minocycline for Multiple Sclerosis therapy. PECs with CSOX enable covalent crosslinking to HAOX, creating immobilized PECs (HAOX_PECOX), while those with CS remain unbound (HAOX_PECS). The in situ forming DDS can be administered via a 20 G needle, with rapid gelation preventing premature leakage. The system integrates into an implanted device for minocycline release through either Fickian or anomalous diffusion, depending on PEC immobilization. HAOX_PECOX reduced burst release by 88 %, with a duration of 127 h for 50 % release. The DDS exhibited an elastic modulus of 3800 Pa and a low swelling ratio (0-1 %), enabling precise control of minocycline release kinetics. Released minocycline reduced IL-6 secretion in the Whole Blood Monocytes Activation Test, suggesting that DDS formation may not alter the biological activity of the loaded drug.
- MeSH
- aldehydy chemie MeSH
- chondroitinsulfáty * chemie MeSH
- hydrogely * chemie farmakologie MeSH
- interleukin-6 metabolismus MeSH
- kyselina hyaluronová * chemie MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- minocyklin * chemie farmakologie aplikace a dávkování MeSH
- nosiče léků * chemie MeSH
- polyelektrolyty * chemie MeSH
- uvolňování léčiv MeSH
- želatina * chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In recent years, multifunctional nanocarriers that provide simultaneous drug delivery and imaging have attracted enormous attention, especially in cancer treatment. In this research, a biocompatible fluorescent multifunctional nanocarrier is designed for the co-delivery of capsaicin (CPS) and nitrogen-doped graphene quantum dots (N-GQDs) using the pH sensitive amphiphilic block copolymer (poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone), PEtOx-b-PCL). The effects of the critical formulation parameters (the amount of copolymer, the concentration of poly(vinyl alcohol) (PVA) as a stabilizing agent in the inner aqueous phase, and volume of the inner phase) are evaluated to achieve optimal nanoparticle (NP) properties using Central Composite Design. The optimized NPs demonstrated a desirable size distribution (167.8 ± 1.4 nm) with a negative surface charge (-19.9 ± 0.4) and a suitable loading capacity for CPS (70.80 ± 0.05%). The CPS & N-GQD NPs are found to have remarkable toxicity on human breast adenocarcinoma cell line (MCF-7). The solid fluorescent signal is acquired from cells containing multifunctional NPs, according to the confocal microscope imaging results, confirming the significant cellular uptake. This research illustrates the enormous potential for cellular imaging and enhanced cancer therapy offered by multifunctional nanocarriers that combine drug substances with the novel fluorescent agents.
- MeSH
- dusík * chemie MeSH
- fluorescenční barviva chemie MeSH
- grafit * chemie MeSH
- kapsaicin * chemie farmakologie MeSH
- kvantové tečky * chemie terapeutické užití MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- protinádorové látky * farmakologie chemie MeSH
- teranostická nanomedicína * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
