Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

• Klíčová slova
• PLGA nanospheres, biodegradable nanoparticles, glucocorticoids, liver inflammation, macrophages,
• MeSH
• dexamethason * analogy a deriváty   farmakologie   chemie   MeSH
• játra * cytologie   metabolismus   účinky léků   patologie   MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná * chemie   MeSH
• kyselina polyglykolová * chemie   MeSH
• lékové transportní systémy MeSH
• makrofágy * účinky léků   metabolismus   MeSH
• myši MeSH
• nanokuličky * chemie   MeSH
• nosiče léků chemie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dexamethason * MeSH
• dexamethasone acetate MeSH Prohlížeč
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná * MeSH
• kyselina polyglykolová * MeSH
• nosiče léků MeSH

Many anticancer active pharmaceutical ingredients (APIs), such as paclitaxel (PTX), exhibit poor water solubility, which limits their bioavailability and necessitates the use of excipients. While biodegradable polymeric excipients combined with nanotechnology offer promising solutions, the high cost of polymers and APIs, along with the vast number of potential API-polymer combinations, poses significant challenges in developing effective drug delivery systems (DDS). This study explores the potential of API-polymer phase behavior modeling as part of the design of nanoparticle (NP)-based DDS for PTX using poly(lactide-co-glycolide) (PLGA) and poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG) with varying molecular weights. The phase behavior of PTX-PLGA/PLGA-PEG systems, which reflects the compatibility of PTX with polymeric excipients, was predicted using the Conductor-like Screening Model for Real Solvents (COSMO-RS). To investigate the correlation between the predictions and experimental observations, PTX-PLGA and PEGylated PLGA NPs were prepared via an emulsion-solvent evaporation method with varying initial PTX amounts. The predicted trends in PTX solubility in polymeric excipients were then compared with key NP characteristics, such as drug loading, solid-state properties, and cytotoxicity in HeLa, SKOV-3, and MRC-5 cells. COSMO-RS predictions indicated limited PTX solubility in PLGA, which aligns with experimental observations, where the maximum amorphous PTX loading did not exceed 2 wt%, regardless of the polymer molecular weight. COSMO-RS modeling predicted higher compatibility of PTX with PEG, suggesting that incorporating PEG would enhance PTX loading in PEGylated NPs. This trend was corroborated by experimental findings, which showed increased drug loading capacity and slower PTX release from PEGylated NPs during cytotoxicity studies. These results highlight the potential of API-polymer modeling as a tool for tailoring polymeric carriers and optimizing API consumption in NP-based DDS development.

• Klíčová slova
• COSMO-RS, Cell tests, Compatibility, Drug delivery systems, Nanoparticles, PLGA copolymers, Paclitaxel,
• MeSH
• fytogenní protinádorové látky * chemie   aplikace a dávkování   farmakologie   MeSH
• kopolymer kyseliny glykolové a mléčné * chemie   MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nanočástice * chemie   aplikace a dávkování   MeSH
• nosiče léků * chemie   MeSH
• paclitaxel * chemie   aplikace a dávkování   farmakologie   MeSH
• polyethylenglykoly chemie   MeSH
• polyglactin 910 * chemie   MeSH
• pomocné látky chemie   MeSH
• rozpustnost MeSH
• uvolňování léčiv MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fytogenní protinádorové látky * MeSH
• kopolymer kyseliny glykolové a mléčné * MeSH
• nosiče léků * MeSH
• paclitaxel * MeSH
• polyethylenglykoly MeSH
• polyglactin 910 * MeSH
• pomocné látky MeSH

Despite the obvious benefits of using ureteral stents to drain the ureters, there is also a risk of complications from 80-90%. The presence of a foreign body in the human body causes disturbances in its proper functioning. It can lead to biofilm formation on the stent surface, which may favor the development of urinary tract infections or the formation of encrustation, as well as stent fragmentation, complicating its subsequent removal. In this work, the effect of the polymeric coating containing the active substance-papaverine hydrochloride on the functional properties of ureteral stents significant for clinical practice were assessed. Methods: The most commonly clinically used polyurethane ureteral Double-J stent was selected for the study. Using the dip-coating method, the surface of the stent was coated with a poly(D,L-lactide-glycolide) (PLGA) coating containing the papaverine hydrochloride (PAP). In particular, strength properties, retention strength of the stent ends, dynamic frictional force, and the fluoroscopic visibility of the stent during X-ray imaging were determined. Results: The analysis of the test results indicates the usefulness of a biodegradable polymer coating containing the active substance for the modification of the surface of polyurethane ureteral stents. The stents coated with PLGA+PAP coating compared to polyurethane stents are characterized by more favorable strength properties, the smaller value of the dynamic frictional force, without reducing the fluoroscopic visibility.

• Klíčová slova
• PLGA with papaverine hydrochloride coatings, break strength, dynamic frictional force, radiopacity, retention strength, ureteral stent,
• MeSH
• biokompatibilní materiály farmakologie   MeSH
• kopolymer kyseliny glykolové a mléčné farmakologie   MeSH
• lidé MeSH
• obstrukce močovodu metabolismus   chirurgie   terapie   MeSH
• papaverin metabolismus   farmakologie   MeSH
• polyurethany chemie   MeSH
• stenty uvolňující léky * MeSH
• vstřebatelné implantáty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• papaverin MeSH
• polyurethany MeSH

Microparticles based on biodegradable synthetic lactic acid and glycolic acid copolymer (PLGA) were successfully prepared by the solvent evaporation method. Ibuprofen was chosen as the model drug. Various formulation and process parameters have been used to prepare each sample with emphasis on size reduction. The effect of the emulsification method (direct emulsification or emulsification using an ULTRA-TURRAX or a NE-1000 dispenser), the volume of the aqueous phase (200, 800 ml) and the stirring speed of the emulsion system (600, 1000 rpm) on the characteristic properties of microparticles, such as encapsulation efficiency, drug loading and particle morphology, was observed. The resulting microparticles were evaluated by optical microscopy or laser diffraction and the dissolution test was performed. It was found that the sample prepared by direct emulsification with 800 ml of an aqueous phase at 600 rpm provided the most favorable results, meanwhile the emulsification pre-step using a homogenizer caused promising particle size reduction. Gradual emulsification was evaluated as inapplicable due to great losses. Key words: microparticles solvent evaporation PLGA ibuprofen size reduction.

• Klíčová slova
• PLGA, ibuprofen, microparticles, size reduction, solvent evaporation,
• MeSH
• ibuprofen * MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina polyglykolová * MeSH
• mikrosféry MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ibuprofen * MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina polyglykolová * MeSH

In this experimental study, the biodegradable polylactide-co-glycolide (PLGA) microparticles (MP) loaded with the insoluble antidepressant mirtazapine were prepared by the simple o/w solvent evaporation method. The formation involved intrinsic variables, such as the content of polymer (700, 900 or 1200 mg), dichloromethane (5 or 10 ml) and/or drug (200 or 400 or 600 mg), and the volume of the aqueous emulsion phase (400, 600 or 800 ml). The influence of these parameters on the size and morphology of microparticles, encapsulation efficiency, and drug release behavior was observed. All MP were successfully prepared, and their size ranged between 165.34 ± 42.88 and 360.17 ± 121.59 μm. MP exhibited prolonged drug release (days), and some profiles had multiphasic character. It was found that the samples prepared with a higher initial amount of PLGA were bigger with prolonged lag time up to 34.3 hours. On the other hand, higher drug concentrations reduced the lag time. The external phase volume reduction and multiplication of dichloromethane amount prolonged the mirtazapine release and decreased the encapsulation efficiency. These observations were further confirmed by multivariate data analysis.

• Klíčová slova
• PLGA, microparticles, mirtazapine, multivariate data analysis, solvent evaporation method,
• MeSH
• antidepresiva MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná * MeSH
• kyselina polyglykolová * MeSH
• mikrosféry MeSH
• mirtazapin MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná * MeSH
• kyselina polyglykolová * MeSH
• mirtazapin MeSH

Despite several shortcomings such as extreme hydrophobicity, low drug capacity, characteristic triphasic drug release pattern with a high burst effect, poly(lactic-co-glycolic acid derivatives are widely used in drug delivery. Most frequent attempts to improve their properties are blending with other polymers or synthesis of block copolymers. We introduce a new class of branched poly(lactic-co-glycolic acid) derivatives as promising biodegradable carriers for prolonged or targeted drug release systems, employed as thin adhesive films, solid dispersions, in situ forming implants or nanoparticles. A series of poly(lactic-co-glycolic acid) derivatives with lower molar mass and star or comb architecture were synthesized by a simple, catalyst free, direct melt polycondensation method not requiring purification of the obtained sterile product by precipitation. Branching monomers used were mannitol, pentaerythritol, dipentaerythritol, tripentaerythritol and polyacrylic acid. The products were characterized by molar mass averages, average branching ratio, rheological and thermal properties.

• Klíčová slova
• PLGA, branching, light scattering, polymer synthesis, star polymer,
• MeSH
• farmaceutická chemie metody   MeSH
• farmaceutická technologie metody   MeSH
• hydrofobní a hydrofilní interakce MeSH
• kopolymer kyseliny glykolové a mléčné chemie   MeSH
• lékové transportní systémy * MeSH
• nosiče léků chemie   MeSH
• reologie MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kopolymer kyseliny glykolové a mléčné MeSH
• nosiče léků MeSH

Although the systemic administration of terbinafine is quite well tolerated, topical treatment of the local infections is often preferred. New formulation strategies in topical antifungal therapy represent the polymeric nanoparticles (NPs). We successfully employed the originally synthesized PLGA derivatives of branched architectures of various molar masses, branching ratio, and high number of terminal hydroxyl or carboxyl groups for compounding of terbinafine loaded nanoparticles by nanoprecipitation method. Employing the polymers with tailored properties allowed us to formulate the NPs with desired particle size, loading capacity for drug, mucoadhesive properties, and drug release profile. The hydrophobicity and the polyester concentration revealed the main impact on the NPs size ranging from 100 to 600 nm. The stability of the nanosuspension is demonstrated by zeta potential >25 mV, and polydispersity index values <0.2. We used terbinafine in its less dissolved form of the base to increase the drug loading and delay the release. Cationic surfactant as stabilizer give the NPs high positive surface charge enhancing the adhesion to the mucosal surfaces. All formulations provided prolonged sustained release of terbinafine for several days. Antimicrobial potential has been proven by agar-well diffusion method.

• Klíčová slova
• Cationic nanoparticles, PLGA, branched polyesters, drug release, nanoprecipitation, terbinafine,
• MeSH
• antifungální látky aplikace a dávkování   chemie   MeSH
• aplikace lokální MeSH
• hydrofobní a hydrofilní interakce MeSH
• kationty MeSH
• kopolymer kyseliny glykolové a mléčné chemie   MeSH
• nanočástice chemie   MeSH
• nosiče léků chemie   MeSH
• povrchově aktivní látky chemie   MeSH
• povrchové vlastnosti MeSH
• příprava léků metody   MeSH
• rozpustnost MeSH
• terbinafin aplikace a dávkování   chemie   MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• viskozita MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky MeSH
• kationty MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• nosiče léků MeSH
• povrchově aktivní látky MeSH
• terbinafin MeSH

The aim of the study was to prepare PLGA microparticles for prolonged release of mirtazapine by o/w solvent evaporation method and to evaluate effects of PVA concentration and organic solvent choice on microparticles characteristics (encapsulation efficiency, drug loading, burst effect, microparticle morphology). Also in vitro drug release tests were performed and the results were correlated with kinetic model equations to approximate drug release mechanism. It was found that dichloromethane provided microparticles with better qualities (encapsulation efficiency 64.2%, yield 79.7%). Interaction between organic solvent effect and effect of PVA concentration was revealed. The prepared samples released the drug for 5 days with kinetics very close to that of zero order (R(2 )= 0.9549 - 0.9816). According to the correlations, the drug was probably released by a combination of diffusion and surface erosion, enhanced by polymer swelling and chain relaxation.

• Klíčová slova
• Drug release, PLGA, kinetics, solvent evaporation method,
• MeSH
• antidepresiva chemie   MeSH
• kinetika MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• methylenchlorid chemie   MeSH
• mianserin analogy a deriváty   chemie   MeSH
• mikrosféry MeSH
• mirtazapin MeSH
• rozpouštědla chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH
• léky s prodlouženým účinkem MeSH
• methylenchlorid MeSH
• mianserin MeSH
• mirtazapin MeSH
• rozpouštědla MeSH

Poly lactic-co-glycolic acid (PLGA) particles safely and effectively deliver pharmaceutical ingredients, with many applications approved for clinical use in humans. In fishes, PLGA particles are being considered as carriers of therapeutic drugs and vaccine antigens. However, existing studies focus mainly on vaccine antigens, the endpoint immune responses to these (e.g., improved antibody titres), without deeper understanding of whether fishes react to the carrier. To test whether or not PLGA are recognized by or interact at all with the immune system of a teleost fish, we prepared, characterized and injected PLGA microparticles intraperitoneally into common carp. The influx, phenotype of inflammatory leukocytes, and their capacity to produce reactive oxygen species and phagocytose PLGA microparticles were tested by flow cytometry, qPCR, and microscopy. PLGA microparticles were indeed recognized. However, they induced only transient recruitment of inflammatory leukocytes that was resolved 4 days later whereas only the smallest µm-sized particles were phagocytosed. The overall response resembled that described in mammals against foreign materials. Given the similarities between our findings and those described in mammals, PLGA particles can be adapted to play a dual role as both antigen and drug carriers in fishes, depending on the administered dose and their design.

• Klíčová slova
• PLGA, antigen, aquaculture, carrier, common carp, foreign body, inflammation, microparticle, teleost fish, vaccine,
• MeSH
• antigeny MeSH
• glykoly MeSH
• imunita MeSH
• kapři * MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH
• savci MeSH
• vakcíny * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny MeSH
• glykoly MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH
• vakcíny * MeSH

A film-forming system (FFS) represents a convenient topical dosage form for drug delivery. In this study, a non-commercial poly(lactic-co-glycolic acid) (PLGA) was chosen to formulate an FFS containing salicylic acid (SA) and methyl salicylate (MS). This unique combination is advantageous from a therapeutic point of view, as it enabled modified salicylate release. It is beneficial from a technological perspective too, because it improved thermal, rheological, and adhesive properties of the in situ film. DSC revealed complete dissolution of SA and good miscibility of MS with the polymer. MS also ensures optimal viscoelastic and adhesive properties of the film, leading to prolonged and sustained drug release. The hydrolysis of MS to active SA was very slow at skin pH 5.5, but it apparently occurred at physiological pH 7.4. The film structure is homogeneous without cracks, unlike some commercial preparations. The dissolution study of salicylates revealed different courses in their release and the influence of MS concentration in the film. The formulated PLGA-based FFS containing 5 % SA and 10 % MS is promising for sustained and prolonged local delivery of salicylates, used mainly for keratolytic and anti-inflammatory actions and pain relief.

• Klíčová slova
• Bioadhesion, Film-forming system, Methyl salicylate, PLGA, Salicylic acid, Sustained drug release,
• MeSH
• aplikace kožní MeSH
• aplikace lokální MeSH
• farmaceutická chemie metody   MeSH
• koncentrace vodíkových iontů MeSH
• kopolymer kyseliny glykolové a mléčné * chemie   MeSH
• kůže metabolismus   MeSH
• kyselina mléčná * chemie   MeSH
• kyselina polyglykolová * chemie   MeSH
• kyselina salicylová * aplikace a dávkování   chemie   farmakokinetika   MeSH
• lékové transportní systémy * metody   MeSH
• léky s prodlouženým účinkem MeSH
• rozpustnost MeSH
• salicylany * aplikace a dávkování   chemie   farmakokinetika   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methyl salicylate MeSH Prohlížeč