Kristina Nesporova - Academia.edu (original) (raw)

Papers by Kristina Nesporova

L'invention concerne un film biodegradable autoportant, comprenant un derive C 10 -C 22 -acyl... more L'invention concerne un film biodegradable autoportant, comprenant un derive C 10 -C 22 -acyle d'acide hyaluronique selon la formule generale (I), ou R represente H + ou Na + , et ou R 1 represente H ou -C(=O)C x H y , ou x est un nombre entier dans la plage de 9 a 21 et y est un nombre entier dans la plage de 11 a 43 et C x H y represente une chaine lineaire ou ramifiee, saturee ou insaturee en C 9 -C 21 , au moins un motif recurrent de R 1 etant -C(=O)C x H y et ou n se situe dans la plage de 12 a 4000; un procede de preparation correspondant et une utilisation correspondante.

Řeseni se týka konjugatů oligomeru kyseliny hyaluronove obecných vzorců I, II, III nebo IV, nebo... more Řeseni se týka konjugatů oligomeru kyseliny hyaluronove obecných vzorců I, II, III nebo IV, nebo jeji soli, způsobu jejich připravy a použiti, kde oligomer je napojen na přislusný substrat svým koncovým anomernim centrem přes bifunkcni aminolinker pomoci amino respektive imino vazby. Tento typ konjugatů umožňuje uvolněni oligomerů v jejich nativni podobě. Připravene systemy vykazaly zvýsenou biologickou aktivitu proti vybraným liniim rakovinových buněk.

Carbohydrate Polymers, 2021

There is inconsistent information regarding the size effects of exogenously given hyaluronan on i... more There is inconsistent information regarding the size effects of exogenously given hyaluronan on its in vivo fate. The data are often biased by the poor quality of hyaluronan and non-ideal labelling strategies used for resolving exogenous/endogenous hyaluronan, which only monitor the label and not hyaluronan itself. To overcome these drawbacks and establish the pharmacokinetics of intravenous hyaluronan in relation to its Mw, 13C-labelled HA of five Mws from 13.6-1562 kDa was prepared and administered to mice at doses 25-50 mg kg-1. The elimination efficiency increased with decreasing Mw. Low Mw hyaluronan was rapidly eliminated as small hyaluronan fragments in urine, while high Mw hyaluronan exhibited saturable kinetics and complete metabolization within 48 h. All tested Mws exhibited a similar uptake by liver cells and metabolization into activated sugars. 13C-labelling combined with LC-MS provides an excellent approach to elucidating in vivo fate and biological activities of hyaluronan.

Carbohydrate Polymers, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of Cellular Physiology, 2018

The stimulation of myocardium repair is restricted due to the limited understanding of heart rege... more The stimulation of myocardium repair is restricted due to the limited understanding of heart regeneration. Interestingly, endogenous opioid peptides such as dynorphins and enkephalins are suggested to support this process. However, the mechanism—whether through the stimulation of the regenerative capacity of cardiac stem cells or through effects on other cell types in the heart—is still not completely understood. Thus, a model of the spontaneous cardiomyogenic differentiation of mouse embryonic stem (mES) cells via the formation of embryoid bodies was used to describe changes in the expression and localization of opioid receptors within cells during the differentiation process and the potential of the selected opioid peptides, dynorphin A and B, and methionin‐enkephalins and leucin‐enkephalins, to modulate cardiomyogenic differentiation in vitro. The expressions of both κ‐ and δ‐opioid receptors significantly increased during mES cell differentiation. Moreover, their primary colocal...

International Journal of Biological Macromolecules, 2017

Hyaluronan (HA) effects on immune response are suggested to be dependent on HA molecular weight (... more Hyaluronan (HA) effects on immune response are suggested to be dependent on HA molecular weight (MW), as low MW HA should activate immune cells in contrast to high MW HA. However, some current studies do not support this conception and emphasize the importance of the form of preparation of HA, particularly with respect to its purity and origin. We compared the activation of mouse immune cells by HA samples (100 kDa, 500 kDa, and 997 kDa) prepared from HA originating from rooster comb, and HA samples (71 kDa, 500 kDa, and 1000 kDa) prepared from pharmacological grade HA originating from Streptococcus equi. Interestingly, in contrast to established theory, only middle and high MW HA originating from rooster comb induced the production of tumor necrosis factor-␣ by macrophages and in whole blood. Further, all tested preparations of HA failed to induce the expression of inducible nitric oxide synthase, the production of nitric oxide, or the expression of cyclooxygenase 2 in macrophages and splenocytes. Importantly, all HA samples originating from rooster comb were found to be contaminated by endotoxin (up to 1.23 EU/ml). Hence, low MW HA did not reveal itself to have significantly higher immunostimulatory activity compared to HA of higher MW.

Carbohydrate Polymers, 2017

Nanosized materials offer promising strategy for topical drug delivery due to their enhancing eff... more Nanosized materials offer promising strategy for topical drug delivery due to their enhancing effect on drug percutaneous transport across the stratum corneum barrier. In this work, polymeric micelles made from hydrophobized hyaluronic acid (HA) were probed for skin delivery. Compared to non-polymeric micelle solutions containing similar drug amount, in vitro skin penetration analysis indicated 3 times larger deposition of drug in the epidermis and 6 times larger drug deposition in the dermis after 5h of topical treatment in Franz diffusion cells. The drug deposition was further increased with prolonged time of topical treatment. Laser confocal microscopy revealed the accumulation of both, the HA forming the vehicle and the payload, in the epidermis and dermis. Although fluorescent labeling of the HA would suggest co-transport of the HA and the drug, loading FRET pair dyes in the micellar core clearly demonstrated gradual micelle disruption with increasing skin depth. Transcellular penetration was the predominant pathway for the loaded drug. The HA polymeric micelles also demonstrated increased bioactivity of loaded compound in vitro and in vivo. In addition, the loaded micelles were found to be stable in cream formulations and thus they have great potential for topical applications for cosmetic and pharmaceutical purposes.

Frontiers in Bioengineering and Biotechnology, 2016

Materials, 2020

The achievement of rapid hemostasis represents a long-term trend in hemostatic research. Specific... more The achievement of rapid hemostasis represents a long-term trend in hemostatic research. Specifically, composite materials are now the focus of attention, based on the given issues and required properties. In urology, different materials are used to achieve fast and effective hemostasis. Additionally, it is desirable to exert a positive influence on local tissue reaction. In this study, three nonwoven textiles prepared by a wet spinning method and based on a combination of hyaluronic acid with either oxidized cellulose or carboxymethyl cellulose, along with the addition of etamsylate, were introduced and assessed in vivo using the rat partial nephrectomy model. A significantly shorter time to hemostasis in seconds (p < 0.05), was attributed to the effect of the carboxymethyl cellulose material. The addition of etamsylate did not noticeably contribute to further hemostasis, but its application strengthened the structure and therefore significantly improved the effect on local chan...

Biomolecules

The physical stresses during cryopreservation affect stem cell survival and further proliferation... more The physical stresses during cryopreservation affect stem cell survival and further proliferation. To minimize or prevent cryoinjury, cryoprotective agents (CPAs) are indispensable. Despite the widespread use of 10% dimethyl sulfoxide (DMSO), there are concerns about its potential adverse effects. To bypass those effects, combinations of CPAs have been investigated. This study aimed to verify whether high-molecular-hyaluronic acid (HMW-HA) serves as a cryoprotectant when preserving human mesenchymal stem cells (hMSCs) to reduce the DMSO concentration in the cryopreservation medium. We studied how 0.1% or 0.2% HMW-HA combined with reduced DMSO concentrations (from 10% to 5%, and 3%) affected total cell count, viability, immunophenotype, and differentiation potential post-cryopreservation. Immediately after cell revival, the highest total cell count was observed in 10% DMSO-stored hMSC. However, two weeks after cell cultivation an increased cell count was seen in the HMW-HA-stored gro...

Biomolecules, 2022

Hyaluronan (HA) comprises a fundamental component of the extracellular matrix and participates in... more Hyaluronan (HA) comprises a fundamental component of the extracellular matrix and participates in a variety of biological processes. Half of the total amount of HA in the human body is present in the skin. HA exhibits a dynamic turnover; its half-life in the skin is less than one day. Nevertheless, the specific participants in the catabolism of HA in the skin have not yet been described in detail, despite the essential role of HA in cutaneous biology. A deeper knowledge of the processes involved will act to support the development of HA-based topical and implantable materials and enhance the understanding of the various related pathological cutaneous conditions. This study aimed to characterize the distribution and activity of hyaluronidases and the other proteins involved in the degradation of HA in healthy human full-thickness skin, the epidermis and the dermis. Hyaluronidase activity was detected for the first time in healthy human skin. The degradation of HA occurred in lysates ...

Biomolecules

All-trans-retinoic acid (atRA) is a potent ligand that regulates gene expression and is used to t... more All-trans-retinoic acid (atRA) is a potent ligand that regulates gene expression and is used to treat several skin disorders. Hyaluronic acid (HA) was previously conjugated with atRA (HA-atRA) to obtain a novel amphiphilic compound. HA-atRA forms micelles that incorporate hydrophobic molecules and facilitate their transport through the skin. The aim of this study was to determine the influence of HA-atRA on gene expression in skin cells and to compare it with that of unbound atRA. Gene expression was investigated using microarrays and a luciferase system with a canonical atRA promoter. HA-atRA upregulated gene expression similarly to atRA. However, HA-atRA activated the expression of cholesterol metabolism genes, unlike atRA. Further investigation using HPLC and filipin III staining suggested that the treated cells induced cholesterol synthesis to replenish the cholesterol removed from the cells by HA-atRA. HA modified with oleate (HA-C18:1) removed cholesterol from the cells simila...

Biomolecules

Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdomina... more Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs—mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This revi...

Řeseni se týka připravy a použiti .alfa.,.beta.-nenasyceneho aldehydu hyaluronanu s dvojnou vazb... more Řeseni se týka připravy a použiti .alfa.,.beta.-nenasyceneho aldehydu hyaluronanu s dvojnou vazbou v polohach 4 a 5 a aldehydickou skupinou v poloze 6 glukosaminove casti polysacharidu podle strukturniho vzorce X nebo jeho hydratovane formy podle strukturniho vzorce Y. Způsob připravy je založen na dehydrataci hyaluronanu s aldehydickou skupinou v poloze 6 glukosaminove casti polysacharidu. Byly popsany dvě metody, a to dehydratace v roztoku, anebo zahřati v suchem stavu bez přitomnosti rozpoustědel, bazi nebo jiných aditiv. Tento derivat umožňuje stabilizovat konjugaty hyaluronanu s aminoslouceninami pomoci nasobne vazby ze strany aldehydu, takže na takto modifikovaný hyaluronan je možne efektivně imobilizovat ve fyziologických podminkach prakticky jakoukoliv slouceninu obsahujici amino skupinu. V připadě použiti diaminu nebo sloucenin připadně polymerů s obsahem tři nebo vic aminoskupin, je možne připravit siťovane derivaty hyaluronanu. Popsane řeseni dava významnou výhodu nejeno...

Řeseni se týka způsobu připravy hydrofobizovaneho hyaluronanu (vzorec I) a dale způsobu enkapsul... more Řeseni se týka způsobu připravy hydrofobizovaneho hyaluronanu (vzorec I) a dale způsobu enkapsulace biologicky aktivnich latek do nanomicel hydrofobizovaneho hyaluronanu sloužiciho jako nosice biologicky aktivnich hydrofobnich latek. Hydrofobizace hyaluronanu je provedena esterifikacni reakci hyaluronanu s karboxylovými kyselinami s dlouhými řetězci, ktere jsou aktivovany halogenidovým derivatem kyseliny 2,4,6-trichlorbenzoove nebo jiným organickým chloridem. Ve vodě rozpustne hydrofobizovane hyaluronany mohou ve vodnem prostředi vytvařet nanomicely, ve kterých mohou být nekovalentně fyzikalnimi interakcemi navazany nepolarni latky. Jadro nanomicely tvoři hydrofobni funkcni skupiny acylu, zatimco obal nanomicely tvoři hyaluronan. Enkapsulaci latek do nanomicel lze provest metodou výměny rozpoustědel nebo sonikaci. Hyaluronove nanomicely podporuji penetraci navazaných latek při topických aplikacich a umožňuji transfer navazaných latek do buněk. Nanomicely z hydrofobizovaných hyaluro...

L'invention concerne un film biodegradable autoportant, comprenant un derive C 10 -C 22 -acyl... more L'invention concerne un film biodegradable autoportant, comprenant un derive C 10 -C 22 -acyle d'acide hyaluronique selon la formule generale (I), ou R represente H + ou Na + , et ou R 1 represente H ou -C(=O)C x H y , ou x est un nombre entier dans la plage de 9 a 21 et y est un nombre entier dans la plage de 11 a 43 et C x H y represente une chaine lineaire ou ramifiee, saturee ou insaturee en C 9 -C 21 , au moins un motif recurrent de R 1 etant -C(=O)C x H y et ou n se situe dans la plage de 12 a 4000; un procede de preparation correspondant et une utilisation correspondante.

Řeseni se týka konjugatů oligomeru kyseliny hyaluronove obecných vzorců I, II, III nebo IV, nebo... more Řeseni se týka konjugatů oligomeru kyseliny hyaluronove obecných vzorců I, II, III nebo IV, nebo jeji soli, způsobu jejich připravy a použiti, kde oligomer je napojen na přislusný substrat svým koncovým anomernim centrem přes bifunkcni aminolinker pomoci amino respektive imino vazby. Tento typ konjugatů umožňuje uvolněni oligomerů v jejich nativni podobě. Připravene systemy vykazaly zvýsenou biologickou aktivitu proti vybraným liniim rakovinových buněk.

Carbohydrate Polymers, 2021

There is inconsistent information regarding the size effects of exogenously given hyaluronan on i... more There is inconsistent information regarding the size effects of exogenously given hyaluronan on its in vivo fate. The data are often biased by the poor quality of hyaluronan and non-ideal labelling strategies used for resolving exogenous/endogenous hyaluronan, which only monitor the label and not hyaluronan itself. To overcome these drawbacks and establish the pharmacokinetics of intravenous hyaluronan in relation to its Mw, 13C-labelled HA of five Mws from 13.6-1562 kDa was prepared and administered to mice at doses 25-50 mg kg-1. The elimination efficiency increased with decreasing Mw. Low Mw hyaluronan was rapidly eliminated as small hyaluronan fragments in urine, while high Mw hyaluronan exhibited saturable kinetics and complete metabolization within 48 h. All tested Mws exhibited a similar uptake by liver cells and metabolization into activated sugars. 13C-labelling combined with LC-MS provides an excellent approach to elucidating in vivo fate and biological activities of hyaluronan.

Carbohydrate Polymers, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of Cellular Physiology, 2018

The stimulation of myocardium repair is restricted due to the limited understanding of heart rege... more The stimulation of myocardium repair is restricted due to the limited understanding of heart regeneration. Interestingly, endogenous opioid peptides such as dynorphins and enkephalins are suggested to support this process. However, the mechanism—whether through the stimulation of the regenerative capacity of cardiac stem cells or through effects on other cell types in the heart—is still not completely understood. Thus, a model of the spontaneous cardiomyogenic differentiation of mouse embryonic stem (mES) cells via the formation of embryoid bodies was used to describe changes in the expression and localization of opioid receptors within cells during the differentiation process and the potential of the selected opioid peptides, dynorphin A and B, and methionin‐enkephalins and leucin‐enkephalins, to modulate cardiomyogenic differentiation in vitro. The expressions of both κ‐ and δ‐opioid receptors significantly increased during mES cell differentiation. Moreover, their primary colocal...

International Journal of Biological Macromolecules, 2017

Hyaluronan (HA) effects on immune response are suggested to be dependent on HA molecular weight (... more Hyaluronan (HA) effects on immune response are suggested to be dependent on HA molecular weight (MW), as low MW HA should activate immune cells in contrast to high MW HA. However, some current studies do not support this conception and emphasize the importance of the form of preparation of HA, particularly with respect to its purity and origin. We compared the activation of mouse immune cells by HA samples (100 kDa, 500 kDa, and 997 kDa) prepared from HA originating from rooster comb, and HA samples (71 kDa, 500 kDa, and 1000 kDa) prepared from pharmacological grade HA originating from Streptococcus equi. Interestingly, in contrast to established theory, only middle and high MW HA originating from rooster comb induced the production of tumor necrosis factor-␣ by macrophages and in whole blood. Further, all tested preparations of HA failed to induce the expression of inducible nitric oxide synthase, the production of nitric oxide, or the expression of cyclooxygenase 2 in macrophages and splenocytes. Importantly, all HA samples originating from rooster comb were found to be contaminated by endotoxin (up to 1.23 EU/ml). Hence, low MW HA did not reveal itself to have significantly higher immunostimulatory activity compared to HA of higher MW.

Carbohydrate Polymers, 2017

Nanosized materials offer promising strategy for topical drug delivery due to their enhancing eff... more Nanosized materials offer promising strategy for topical drug delivery due to their enhancing effect on drug percutaneous transport across the stratum corneum barrier. In this work, polymeric micelles made from hydrophobized hyaluronic acid (HA) were probed for skin delivery. Compared to non-polymeric micelle solutions containing similar drug amount, in vitro skin penetration analysis indicated 3 times larger deposition of drug in the epidermis and 6 times larger drug deposition in the dermis after 5h of topical treatment in Franz diffusion cells. The drug deposition was further increased with prolonged time of topical treatment. Laser confocal microscopy revealed the accumulation of both, the HA forming the vehicle and the payload, in the epidermis and dermis. Although fluorescent labeling of the HA would suggest co-transport of the HA and the drug, loading FRET pair dyes in the micellar core clearly demonstrated gradual micelle disruption with increasing skin depth. Transcellular penetration was the predominant pathway for the loaded drug. The HA polymeric micelles also demonstrated increased bioactivity of loaded compound in vitro and in vivo. In addition, the loaded micelles were found to be stable in cream formulations and thus they have great potential for topical applications for cosmetic and pharmaceutical purposes.

Frontiers in Bioengineering and Biotechnology, 2016

Materials, 2020

The achievement of rapid hemostasis represents a long-term trend in hemostatic research. Specific... more The achievement of rapid hemostasis represents a long-term trend in hemostatic research. Specifically, composite materials are now the focus of attention, based on the given issues and required properties. In urology, different materials are used to achieve fast and effective hemostasis. Additionally, it is desirable to exert a positive influence on local tissue reaction. In this study, three nonwoven textiles prepared by a wet spinning method and based on a combination of hyaluronic acid with either oxidized cellulose or carboxymethyl cellulose, along with the addition of etamsylate, were introduced and assessed in vivo using the rat partial nephrectomy model. A significantly shorter time to hemostasis in seconds (p < 0.05), was attributed to the effect of the carboxymethyl cellulose material. The addition of etamsylate did not noticeably contribute to further hemostasis, but its application strengthened the structure and therefore significantly improved the effect on local chan...

Biomolecules

The physical stresses during cryopreservation affect stem cell survival and further proliferation... more The physical stresses during cryopreservation affect stem cell survival and further proliferation. To minimize or prevent cryoinjury, cryoprotective agents (CPAs) are indispensable. Despite the widespread use of 10% dimethyl sulfoxide (DMSO), there are concerns about its potential adverse effects. To bypass those effects, combinations of CPAs have been investigated. This study aimed to verify whether high-molecular-hyaluronic acid (HMW-HA) serves as a cryoprotectant when preserving human mesenchymal stem cells (hMSCs) to reduce the DMSO concentration in the cryopreservation medium. We studied how 0.1% or 0.2% HMW-HA combined with reduced DMSO concentrations (from 10% to 5%, and 3%) affected total cell count, viability, immunophenotype, and differentiation potential post-cryopreservation. Immediately after cell revival, the highest total cell count was observed in 10% DMSO-stored hMSC. However, two weeks after cell cultivation an increased cell count was seen in the HMW-HA-stored gro...

Biomolecules, 2022

Hyaluronan (HA) comprises a fundamental component of the extracellular matrix and participates in... more Hyaluronan (HA) comprises a fundamental component of the extracellular matrix and participates in a variety of biological processes. Half of the total amount of HA in the human body is present in the skin. HA exhibits a dynamic turnover; its half-life in the skin is less than one day. Nevertheless, the specific participants in the catabolism of HA in the skin have not yet been described in detail, despite the essential role of HA in cutaneous biology. A deeper knowledge of the processes involved will act to support the development of HA-based topical and implantable materials and enhance the understanding of the various related pathological cutaneous conditions. This study aimed to characterize the distribution and activity of hyaluronidases and the other proteins involved in the degradation of HA in healthy human full-thickness skin, the epidermis and the dermis. Hyaluronidase activity was detected for the first time in healthy human skin. The degradation of HA occurred in lysates ...

Biomolecules

All-trans-retinoic acid (atRA) is a potent ligand that regulates gene expression and is used to t... more All-trans-retinoic acid (atRA) is a potent ligand that regulates gene expression and is used to treat several skin disorders. Hyaluronic acid (HA) was previously conjugated with atRA (HA-atRA) to obtain a novel amphiphilic compound. HA-atRA forms micelles that incorporate hydrophobic molecules and facilitate their transport through the skin. The aim of this study was to determine the influence of HA-atRA on gene expression in skin cells and to compare it with that of unbound atRA. Gene expression was investigated using microarrays and a luciferase system with a canonical atRA promoter. HA-atRA upregulated gene expression similarly to atRA. However, HA-atRA activated the expression of cholesterol metabolism genes, unlike atRA. Further investigation using HPLC and filipin III staining suggested that the treated cells induced cholesterol synthesis to replenish the cholesterol removed from the cells by HA-atRA. HA modified with oleate (HA-C18:1) removed cholesterol from the cells simila...

Biomolecules

Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdomina... more Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs—mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This revi...

Řeseni se týka připravy a použiti .alfa.,.beta.-nenasyceneho aldehydu hyaluronanu s dvojnou vazb... more Řeseni se týka připravy a použiti .alfa.,.beta.-nenasyceneho aldehydu hyaluronanu s dvojnou vazbou v polohach 4 a 5 a aldehydickou skupinou v poloze 6 glukosaminove casti polysacharidu podle strukturniho vzorce X nebo jeho hydratovane formy podle strukturniho vzorce Y. Způsob připravy je založen na dehydrataci hyaluronanu s aldehydickou skupinou v poloze 6 glukosaminove casti polysacharidu. Byly popsany dvě metody, a to dehydratace v roztoku, anebo zahřati v suchem stavu bez přitomnosti rozpoustědel, bazi nebo jiných aditiv. Tento derivat umožňuje stabilizovat konjugaty hyaluronanu s aminoslouceninami pomoci nasobne vazby ze strany aldehydu, takže na takto modifikovaný hyaluronan je možne efektivně imobilizovat ve fyziologických podminkach prakticky jakoukoliv slouceninu obsahujici amino skupinu. V připadě použiti diaminu nebo sloucenin připadně polymerů s obsahem tři nebo vic aminoskupin, je možne připravit siťovane derivaty hyaluronanu. Popsane řeseni dava významnou výhodu nejeno...

Řeseni se týka způsobu připravy hydrofobizovaneho hyaluronanu (vzorec I) a dale způsobu enkapsul... more Řeseni se týka způsobu připravy hydrofobizovaneho hyaluronanu (vzorec I) a dale způsobu enkapsulace biologicky aktivnich latek do nanomicel hydrofobizovaneho hyaluronanu sloužiciho jako nosice biologicky aktivnich hydrofobnich latek. Hydrofobizace hyaluronanu je provedena esterifikacni reakci hyaluronanu s karboxylovými kyselinami s dlouhými řetězci, ktere jsou aktivovany halogenidovým derivatem kyseliny 2,4,6-trichlorbenzoove nebo jiným organickým chloridem. Ve vodě rozpustne hydrofobizovane hyaluronany mohou ve vodnem prostředi vytvařet nanomicely, ve kterých mohou být nekovalentně fyzikalnimi interakcemi navazany nepolarni latky. Jadro nanomicely tvoři hydrofobni funkcni skupiny acylu, zatimco obal nanomicely tvoři hyaluronan. Enkapsulaci latek do nanomicel lze provest metodou výměny rozpoustědel nebo sonikaci. Hyaluronove nanomicely podporuji penetraci navazaných latek při topických aplikacich a umožňuji transfer navazaných latek do buněk. Nanomicely z hydrofobizovaných hyaluro...