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Hyaluronic gels for control release of active substances
Hekrlová, Veronika ; Smilek, Jiří (referee) ; Klučáková, Martina (advisor)
This diploma thesis is focused on the development of materials based on oxidized hyaluronic acid derivative (HA-Ox) crosslinked using bifunctional alkoxyamine POA. Hydrogels have been studied as potential matrices for the controlled release of biological drugs. For this purpose, hydrogels containing bovine serum albumin (BSA) as model of the active substances were prepared. The properties of the hydrogels were affected by the concentration of the derivative (10 mg / ml, 20 mg / ml and 30 mg / ml). In the first part of the work, the viscoelastic properties, swelling and dry matter content of the prepared hydrogels were evaluated. The dry matter of the starting hyaluronan derivative and the weight of the polymer network in the hydrogels were determined gravimetrically and by TGA (in all cases about 80% w/w). The difference in weight of the polymer contained in the hydrogels before and after swelling showed that the non-crosslinked sol leaches out of the hydrogel during swelling (about 10-20% w/w). Due to this phenomenon, hydrogels with a concentration of 10 mg / ml are depleted of hydrogels, while their more concentrated analogues swell even after the sol has washed off. The sizes of elastic moduli needed to calculate the mesh of the polymer network were determined using rheological measurements (amplitude and frequency test). The mesh size of the polymer network itself is calculated using two commonly used theories: Equilibrium SwellingTheory (EST) and Rubber Elasticity Theory (RET). The mesh size of BSA-free gels with a derivative concentration of 10 to 30 mg/ml was determined according to EST to 347 ± 29 nm, 319 ± 15 nm, 295 ± 6 nm and according to RET345 ± 30 nm, 308 ± 14 nm, 268 ± 5 nm. For hydrogels with BSA, the mesh sizes of the polymer network were determined according to EST 373 ± 34 nm, 307 ± 11 nm, 281 ± 7 nm and according to RET 372 ± 32 nm, 297 ± 11 nm, 258 ± 6 nm. The mesh size of the polymer network decreases with higher derivative concentration. In the second part of the work, the release of the model active substance BSA was monitored spectrophotometrically using fluorescent labeling. Using the Korsmeyer-Peppas model, it was found that diffusion release is the primary mechanism.
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Preparation of biodegradable films from PHA copolymers and evaluation of their application potential
Drotárová, Lenka ; Přikryl, Radek (referee) ; Sedláček, Petr (advisor)
This diploma thesis deals with the production of biodegradable PHA copolymer fims and the subsequent study of their material properties. The main goal of this thesis is to assess the application potential of PHA copolymer films in the biomedical industry. The theoretical part of the thesis deals with the characterization of polyhydroxyalkanoates and their copolymers, in terms of physical properties, synthesis, biodegradation or PHA producers. The current research in the processing and use of PHA in biomedicine is described in the literature search. The cultivation of bacterial strains of Aneurinibacillus sp. H1 and Cupriavidus necator H16 was done in the experimental part. Different ratios of glycerol and 1,4-butanediol substrates were used during the cultivation of Aneurinibacillus sp. H1, to obtain copolymers of P(3HB-co-4HB) with a different monomer composition. Polymer films were isolated from the obtained biomass by the extraction method and were characterized by GC-FID, FTIR and SEC-MALS methods. Subsequently, copolymer films containing of 65,25 and 43,61 wt. % 4HB and homopolymer PHB film were selected for release experiments. The drugs, ibuprofen and acetylsalicylic acid, were used for release experiments, their release from the polymer film into the physiological solution was monitored by UV-VIS spectroscopy. Based on the obtained data, the application potential of PHA copolymer films as a carrier system in biomedical use was verified.
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Release of active substances from porous structures based on poly(3-hydroxybutyrate) (PHB)
Černeková, Nicole ; Veselá, Mária (referee) ; Kovalčík, Adriána (advisor)
This bachelor thesis deals with the study of the release of active substances from porous structures based on poly(3-hydroxybutyrate) (P3HB). The theoretical part describes the basic characteristics of polyhydroxyalkanoates, their effect on the organism and method of electrospinning. In the experimental part, solutions of poly(3-hydroxybutyrate) in a solvent mixture of dichloromethane and chloroform were electrospun in three different ratios. The morphology of the formed fibrous porous structures was assessed by scanning electron microscopy, based on which the active substance, the antibiotic Levofloxacin, was incorporated into suitable structures. Antimicrobial activity of the antibiotic released from prepared porous structures was tested by the agar diffusion method against gram-negative bacteria Escherichia coli and Serratia marcescens, the gram-positive bacterium Micrococcus luteus and against the yeast Candida glabrata. The results showed a significant antimicrobial effect of the prepared samples against all bacterial cultures, in the case of the culture of yeasts, no zones of inhibition occurred. Next, the course of the active substance release from the prepared electrospun meshes was studied spectrophotometrically depending on the morphological structure. It was found that the active substance was successfully incorporated into electrospun fibers and the course of the drug release depended on the morphology of P3HB electrospun meshes.
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Methodology for experimental study on the release of humic acids from hydrogel application forms.
Palanová, Veronika ; Klučáková, Martina (referee) ; Sedláček, Petr (advisor)
Hlavnou náplňou bakalárskej práce bolo navrhnúť a optimalizovať metódu experimentálneho štúdia uvoľňovania huminovej látky z gelových matríc, ktoré boli vytvorené pomocou bežných kozmetických a farmaceutických zahusťujúcich látok. Pre štúdium uvoľňovania tejto aktívnej látky bola zvolená difúzna aparatúra vo vertikálnom usporiadaní, tzv. Francova cela. Výluhy gelových vzoriek boli podrobené spektrofotometrickým meraniam. Vzniklé interakcie medzi roztokmi lignohumátu a rôznych typov zahusťujúcich látok boli experimentálne stanovené. Celý proces optimalizácie metódy pre uvoľňovanie huminovej látky z gelových foriem bol diskutovaný.
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Polymeric Materials for the Controlled Drug Delivery and Controlled Release of Active Substances
Chamradová, Ivana ; Kučerík, Jiří (referee) ; Lehocký,, Marián (referee) ; Vojtová, Lucy (advisor)
Literární rešerše předložené dizertační práce shrnuje poznatky jak o současně používaných biomateriálech, tak i o tzv. „chytrých“ biomedicínských materiálech mezi které patří termocitlivé kopolymery. Mezi tyto kopolymery, jejichž vodné roztoky gelují při teplotě lidského těla (37 °C), řadíme amfifilní triblokové kopolymery skládající se z hydrofobního laktidu, glykolidu a hydrofilního polyethylen glykolu (PLGA PEG PLGA). Komerčně dostupné termocitlivé kopolymery známé pod názvem ReGel or OncoGel jsou v současné době využívány jako injekčně aplikovatelné nosiče s postupným uvolňováním léčiv, zejména při léčbě cukrovky nebo onkologického onemocnění. Nicméně PLGA PEG PLGA triblokový kopolymer může být použit I jako polymerní nosič anorganického léčiva případně jako biodegradabilní implantát v dentálních či ortopedickýchých aplikacích. Z toho důvodu byl vybrán anorganický biokompatibilní hydroxyapatit (HAp) pro své majoritní zastoupení v tvrdých tkáních. Experimentální část je zaměřena na přípravu HAp/PLGA PEG PLGA kompozitů, ve kterých je HAp buď ve formě nano- (n-HAp) nebo „core-shell“ částic (CS). Nové CS částice, připravené dvouemulzní metodou, jsou složeny z „tuhého“ HAp jádra obaleného termocitlivým kopolymerem, který je navíc funkcionalizován kyselinou itakonovou (ITA/PLGA PEG PLGA/ITA). Funkcionalizace pomocí ITA vnáší do původní struktury kopolymeru jak síťovatelné dvojné vazby, tak i koncové karboxylové skupiny. Volné karboxylové skupiny na koncích ITA/PLGA PEG PLGA/ITA kopolymerního obalu byly dále zesíťovány za vzniku 3D chemické sítě (CS-x), jejíž životnost je řízena a kontrolována. ATR-FTIR spektroskopie prokázala přítomnost „nových“ esterových vazeb vzniklých karbodiimidovou reakcí –OH a –COOH skupin, kterým náleží adsorpční pásy ve vlnové délce 1021 cm-1.. n-HAp a CS-x částice byly přidány do kopolymerní termocitlivé matrice (PLGA PEG PLGA) za účelem charakterizace jejich reologického chování. Bylo zjištěno, že pokud bylo do polymerní matrice přidáno méně než 10 hm. % CS-x částic a jen 5 hm.% n-HAp kompozit si zachoval své termocitlivé vlastnosti. Na druhou stranu, přídavek vyššího množství HAp částic do polymerní matrice zajistil změnu vodného polymerního solu v permanentní gel při teplotě nad 37 °C. Analýza ICP-OES prokázala rychlejší uvolňování CS-x částic z 10 hm/obj. % PLGA PEG PLGA polymerní matrice do inkubačního média (6 % 9. den) než tomu bylo u n-HAp částic (jen 3 %), které jsou vázány více v micelární struktuře kopolymeru. Proto, kompozit na bázi n-HAP částic tvořící tuhý trvalý gel při tělesné teplotě, je vhodný více jako biologicky rozložitelné kostní lepidlo, zatímco kompozit z CS-x částic a termocitlivého kopolymeru je vhodný jako nosič léčiv pro injekční aplikace.
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Formulation of vancomycin loaded PLGA nanoparticles for local treatment of musculoskeletal infections II.
Ptáčková, Karolína ; Šnejdrová, Eva (advisor) ; Zbytovská, Jarmila (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Karolína Ptáčková Title of thesis: Formulation of vancomycin loaded PLGA nanoparticles for local treatment of musculoskeletal infections II. Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Consultant: Mgr. Vladislav Frolov The aim of the work was to formulate vancomycin hydrochloride (Van-HCl) loaded PLGA nanoparticles (NPs) using a double emulsion method for the local treatment of musculoskeletal infections. During preparation, selected critical formulation factors were modified and their influence on the characteristics of nanoparticles was studied. The size of the NPs determined by the DLS method ranged from 200 to 800 nm, the PDI was lower than 0.2 in most batches. The encapsulation efficiency (EE) determined by the direct method ranged from 2 % to 9 %. Glycerol monostearate at a concentration of 15 mg/ml proved to be a suitable primary emulsion stabilizer. The optimal concentration of PVA for stabilizing the nanosuspension was 30 mg/ml. The size of the NPs was influenced by the intensity of homogenization and the concentration of PVA. The concentration of Van-HCl, the organic solvent used and the intensity of homogenization led to an increase in EE. The DSC method confirmed that Van-HCl remains...
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Formulation of vancomycin loaded PLGA nanoparticles for local treatment of musculoskeletal infections I.
Petrášová, Ivana ; Šnejdrová, Eva (advisor) ; Smékalová, Monika (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Ivana Petrášová Title of thesis: Formulation of PLGA nanoparticles with vancomycin for local treatment of musculoskeletal infections I Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The treatment of musculoskeletal infections requires the presence of high antibiotics concentration at the infection site. However, high doses of orally administered drugs cause the risk of increased systemic toxicity and serious adverse effects. Targeted drug delivery, currently one of the main areas of pharmaceutical research, represents a suitable option of a treatment without excessive burden on the organism. This diploma thesis focuses on the formulation of a therapeutic system for the local treatment of musculoskeletal infections in the form of polymer nanoparticles containing the antibiotic vancomycin. Due to the need of incorporation of a hydrophilic antimicrobial substance into them, the suspension-emulsion method of their preparation was used. Different concentrations of polyvinyl alcohol stabilizer and tripentaerythritol branched hydrophobic polymer poly(D,L- lactide-co-glycolide) were used for the preparation. Within the study the size of nanoparticles, polydispersity, zeta potential, encapsulation efficiency...
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Formulation and characterization of w/o emulsions for local treatment of musculoskeletal infections
Vedralová, Štěpánka ; Šnejdrová, Eva (advisor) ; Mužíková, Jitka (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical technology Author: Štěpánka Vedralová Title of diploma thesis: Formulation and characterization of w/o emulsions for local treatment of musculoskeletal infections Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The aim of the diploma thesis was to formulate a depot dosage form for the prevention and local treatment of musculoskeletal infections. A water-in-oil emulsions have been formulated which, due to the partition coefficient between the outer and inner phases, can provide sustained drug release. Oils with different viscosities were tested as oil phases. Tricaprin was chosen for the preparation of emulsions, due to the highest stability of the prepared emulsion. Lecithin and sorbitan monooleate or polyglyceryl-3-polyricinooleate (PGPR) and magnesium stearate were used as emulsifiers. The aqueous phase was a solution of vancomycin hydrochloride and gentamicin sulphate. The flow properties on a rotational rheometer were evaluated. The influence of the emulsion composition and the homogenization method on the coefficient of consistency and the index of flow behaviour of the emulsions was studied. The emulsions stabilized with lecithin have a higher viscosity and a structure more sensitive to changes in composition...
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Formulation and characterization of hydrogels for local treatment of musculoskeletal infections
Drdová, Pavlína ; Šnejdrová, Eva (advisor) ; Vraníková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Pavlína Drdová Title of thesis: Formulation and characterization of hydrogels for local treatement of musculoskeletal infection Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Local anti-infective therapy for musculoskeletal infections eliminates systemic drug toxicity. By selecting a suitable drug delivery system, higher drug concentrations at the site of infection and sustained release can be achieved. Such a system may be gels, formulated and tested in the submitted diploma thesis. The theoretical part of the work was devoted to the description of musculoskeletal infections and their treatment, characterization of gels and their use in parenteral administration. Hydrophilic gels based on hypromellose, carrageenan, gelatin and fish gelatin containing vamcomycin hydrochloride and gentamicin sulfate were formulated. Flow and viscoelastic properties were tested on a rotational rheometer. The analysis of flow curves by the Power law model proved a non-Newtonian type of flow. The most sensitive to applied stress is a 3 % hypromellose gel, the least a dispersion of iota-carrageenan with povidone 25. Viscoelastic properties were evaluated based on elastic, viscous and complex modulus, phase angle and yield...
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Dissolution of a drug from thin films based on plasticized PLGA derivatives
Kodytková, Simona ; Šnejdrová, Eva (advisor) ; Paraskevopoulou, Anna (referee)
CHARLES UNIVERSITY Faculty od Pharmacy in Hradec Kralove Department od Pharmaceutical Technology Author: Simona Kodytková Title od Diploma thesis: Dissolution of a drug from thin films based on plasticized PLGA derivatives Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The aim of the presented work was to formulate liquid systems for the formulation of in situ thin films (FFS) based on copolymers D,L-lactic and glycolic acid (PLGA) and to study the effect of a combination of salicylic acid and methyl salicylate in film and the effect of their various concentrations on dissolution profiles. The theoretical section summarizes the general knowledge about the characteristics, substances used to formulate FFS and methods for their testing. In the experimental section, liquid systems forming in situ films by solvent evaporation were prepared, based on a linear or branched PLGA polymer containing salicylic acid as a poor water soluble drug, and methyl-salicylate as a multifuctional plasticizer, at different concentrations. The solubility test of salicylic acid, methyl salicylate and their mixtures, and dissolution tests of drug and plasticizer in phosphate buffer buffer pH 5.5 at 37 řC were performed. Salicylate analysis was performed by HPLC. Based on the results, it can be stated that faster dissolution of...
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