scholarly journals Post-Synthetic Enzymatic and Chemical Modifications for Novel Sustainable Polyesters

2022 ◽  
Vol 9 ◽  
Author(s):  
Fady Abd El-malek ◽  
Alexander Steinbüchel
Keyword(s):  
Heat Resistance ◽  
Biodegradable Polymers ◽  
Mechanical Characteristics ◽  
Flexible Structures ◽  
Important Class ◽  
Chemical Modifications ◽  
Application Range ◽  
High Crystallinity

Because of their biodegradability, compostability, compatibility and flexible structures, biodegradable polymers such as polyhydroxyalkanoates (PHA) are an important class of biopolymers with various industrial and biological uses. PHAs are thermoplastic polyesters with a limited processability due to their low heat resistance. Furthermore, due to their high crystallinity, some PHAs are stiff and brittle. These features result sometimes in very poor mechanical characteristics with low extension at break values which limit the application range of some natural PHAs. Several in vivo approaches for PHA copolymer modifications range from polymer production to enhance PHA-based material performance after synthesis. The methods for enzymatic and chemical polymer modifications are aiming at modifying the structures of the polyesters and thereby their characteristics while retaining the biodegradability. This survey illustrates the efficient use of enzymes and chemicals in post-synthetic PHA modifications, offering insights on these green techniques for modifying and improving polymer performance. Important studies in this sector will be reviewed, as well as chances and obstacles for their stability and hyper-production.

Application of self-healing, swellable and biodegradable polymers for wound treatment

2021 ◽  
Vol 30 (Sup9a) ◽  
pp. IVi-IVx
Author(s):  
Chukwuma O Agubata ◽  
Mary A Mbah ◽  
Paul A Akpa ◽  
Godwin Ugwu
Keyword(s):  
Wound Healing ◽  
Polyvinyl Alcohol ◽  
Biodegradable Polymers ◽  
Hydroxypropyl Methylcellulose ◽  
Composite Films ◽  
Self Healing ◽  
Moisture Uptake ◽  
Folding Endurance

Aim: Self-healing, swellable and biodegradable polymers are vital materials that may facilitate the different stages of wound healing. The aim of this research was to prepare wound healing films using self-healing polyvinyl alcohol (PVA), swellable hydroxypropyl methylcellulose (HPMC), biodegradable polyglycolic acid (PGA) sutures and ciprofloxacin antibiotic for improved treatment outcome. Methods: Films were formulated through aqueous-based mixing of varying amounts of polyvinyl alcohol (10–20% weight/weight (w/w)) and hydroxypropyl methylcellulose (0.5, 1% w/w) with fixed quantities of ciprofloxacin. PGA sutures were placed as grids within the wet mixtures of the polymers and ciprofloxacin, and thereafter products were air dried. The formulated films were evaluated for swelling ratio, breaking elongation, folding endurance, moisture uptake and loss, compatibility and in vitro antibiotic release. Furthermore, in vivo wound healing was studied using excision model and histopathological examinations. Results: Swelling ratios were above 1.0 and the films were minimally stretchable, with folding endurance greater than 500. Films were stable while moisture uptake and loss were observed to be less than 30%. Among the optimised hydrogel batches, those containing 10% w/w PVA and 1% w/w HPMC with no PGA showed the highest drug release of 73%, whereas the batches with higher PGA content showed higher percentage wound size reduction with minimal scar. The completeness of wound healing with batches containing PVA, HPMC, ciprofloxacin and PGA, along with the standard, is evident considering the massive cornification, regeneration of the epithelial front and stratum spinosum. Conclusion: The findings show that polymer-based multifunctional composite films are suitable for use as dressings for improved wound healing.

scholarly journals Plasmid DNA-based Alphavirus Vaccines

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 29 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Tumor Cells ◽  
Plasmid Dna ◽  
Transgene Expression ◽  
Tumor Regression ◽  
Infectious Agents ◽  
Application Range ◽  
Mammalian Cell Lines ◽  
High Level ◽  
Rna Replicon

Alphaviruses have been engineered as vectors for high-level transgene expression. Originally, alphavirus-based vectors were applied as recombinant replication-deficient particles, subjected to expression studies in mammalian and non-mammalian cell lines, primary cell cultures, and in vivo. However, vector engineering has expanded the application range to plasmid DNA-based delivery and expression. Immunization studies with DNA-based alphavirus vectors have demonstrated tumor regression and protection against challenges with infectious agents and tumor cells in animal tumor models. The presence of the RNA replicon genes responsible for extensive RNA replication in the RNA/DNA layered alphavirus vectors provides superior transgene expression in comparison to conventional plasmid DNA-based expression. Immunization with alphavirus DNA vectors revealed that 1000-fold less DNA was required to elicit similar immune responses compared to conventional plasmid DNA. In addition to DNA-based delivery, immunization with recombinant alphavirus particles and RNA replicons has demonstrated efficacy in providing protection against lethal challenges by infectious agents and tumor cells.

scholarly journals Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods

Materials ◽  
2018 ◽  
Vol 11 (11) ◽  
pp. 2081 ◽  
Author(s):  
Teddy Tite ◽  
Adrian-Claudiu Popa ◽  
Liliana Balescu ◽  
Iuliana Bogdan ◽  
Iuliana Pasuk ◽  
...  
Keyword(s):  
High Performance ◽  
Life Time ◽  
Crystalline Lattice ◽  
Current Status ◽  
Synthesis Methods ◽  
Biological Interactions ◽  
Application Range ◽  
Biological Performance

High-performance bioceramics are required for preventing failure and prolonging the life-time of bone grafting scaffolds and osseous implants. The proper identification and development of materials with extended functionalities addressing socio-economic needs and health problems constitute important and critical steps at the heart of clinical research. Recent findings in the realm of ion-substituted hydroxyapatite (HA) could pave the road towards significant developments in biomedicine, with an emphasis on a new generation of orthopaedic and dentistry applications, since such bioceramics are able to mimic the structural, compositional and mechanical properties of the bone mineral phase. In fact, the fascinating ability of the HA crystalline lattice to allow for the substitution of calcium ions with a plethora of cationic species has been widely explored in the recent period, with consequent modifications of its physical and chemical features, as well as its functional mechanical and in vitro and in vivo biological performance. A comprehensive inventory of the progresses achieved so far is both opportune and of paramount importance, in order to not only gather and summarize information, but to also allow fellow researchers to compare with ease and filter the best solutions for the cation substitution of HA-based materials and enable the development of multi-functional biomedical designs. The review surveys preparation and synthesis methods, pinpoints all the explored cation dopants, and discloses the full application range of substituted HA. Special attention is dedicated to the antimicrobial efficiency spectrum and cytotoxic trade-off concentration values for various cell lines, highlighting new prophylactic routes for the prevention of implant failure. Importantly, the current in vitro biological tests (widely employed to unveil the biological performance of HA-based materials), and their ability to mimic the in vivo biological interactions, are also critically assessed. Future perspectives are discussed, and a series of recommendations are underlined.

scholarly journals In vivo mucoadhesive strength appraisal of gum Manilkara zapota

2015 ◽  
Vol 51 (3) ◽  
pp. 689-698 ◽  
Author(s):  
Singh Sudarshan ◽  
Bothara Sunil B
Keyword(s):  
Drug Delivery Systems ◽  
Guar Gum ◽  
Methyl Cellulose ◽  
Synthetic Polymers ◽  
Chemical Modifications ◽  
Experimental Conditions ◽  
Manilkara Zapota ◽  
Seed Mucilage

The mucilage (MMZ) extracted from the seeds of Manilkara zapota(Linn.) P. Royen syn. using maceration techniques was evaluated for mucoadhesive strength by various in vitro and in vivo methods. The result showed that mucoadhesive strength of seeds mucilage have comparable property toward natural and synthetic polymers such as Guar Gum and hydroxyl propyl methyl cellulose (HPMC E5LV) under the experimental conditions used in this study. Briefly, it could be concluded that the seed mucilage of Manilkara zapota can be used as a pharmaceutical excipient in oral mucoadhesive drug delivery systems. Further, it may be appropriate to study the changes in these properties after chemical modifications.

scholarly journals In Vivo Chaperone Activity of Heat Shock Protein 70 and Thermotolerance

1999 ◽  
Vol 19 (3) ◽  
pp. 2069-2079 ◽  
Author(s):  
Ellen A. A. Nollen ◽  
Jeanette F. Brunsting ◽  
Han Roelofsen ◽  
Lee A. Weber ◽  
Harm H. Kampinga
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Resistance ◽  
Cell Line ◽  
Heat Shock Protein 70 ◽  
Chaperone Activity ◽  
Luciferase Reporter ◽  
Reporter Protein ◽  
Regulated Gene Expression

ABSTRACT Heat shock protein 70 (Hsp70) is thought to play a critical role in the thermotolerance of mammalian cells, presumably due to its chaperone activity. We examined the chaperone activity and cellular heat resistance of a clonal cell line in which overexpression of Hsp70 was transiently induced by means of the tetracycline-regulated gene expression system. This single-cell-line approach circumvents problems associated with clonal variation and indirect effects resulting from constitutive overexpression of Hsp70. The in vivo chaperone function of Hsp70 was quantitatively investigated by using firefly luciferase as a reporter protein. Chaperone activity was found to strictly correlate to the level of Hsp70 expression. In addition, we observed an Hsp70 concentration dependent increase in the cellular heat resistance. In order to study the contribution of the Hsp70 chaperone activity, heat resistance of cells that expressed tetracycline-regulated Hsp70 was compared to thermotolerant cells expressing the same level of Hsp70 plus all of the other heat shock proteins. Overexpression of Hsp70 alone was sufficient to induce a similar recovery of cytoplasmic luciferase activity, as does expression of all Hsps in thermotolerant cells. However, when the luciferase reporter protein was directed to the nucleus, expression of Hsp70 alone was not sufficient to yield the level of recovery observed in thermotolerant cells. In addition, cells expressing the same level of Hsp70 found in heat-induced thermotolerant cells containing additional Hsps showed increased resistance to thermal killing but were more sensitive than thermotolerant cells. These results suggest that the inducible form of Hsp70 contributes to the stress-tolerant state by increasing the chaperone activity in the cytoplasm. However, its expression alone is apparently insufficient for protection of other subcellular compartments to yield clonal heat resistance to the level observed in thermotolerant cells.

scholarly journals Barcoding chemical modifications into nucleic acids improves drug stability in vivo

2018 ◽  
Vol 6 (44) ◽  
pp. 7197-7203 ◽  
Author(s):  
Cory D. Sago ◽  
Sujay Kalathoor ◽  
Jordan P. Fitzgerald ◽  
Gwyneth N. Lando ◽  
Naima Djeddar ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Drug Stability ◽  
Chemical Modifications

The efficacy of nucleic acid therapies can be limited by unwanted degradation.

scholarly journals In vitro and in vivo properties of therapeutic oligonucleotides containing non-chiral 3′ and 5′ thiophosphate linkages

2019 ◽  
Vol 48 (1) ◽  
pp. 63-74 ◽  
Author(s):  
Jörg Duschmalé ◽  
Henrik Frydenlund Hansen ◽  
Martina Duschmalé ◽  
Erich Koller ◽  
Nanna Albaek ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Rnase H ◽  
Modified Oligonucleotides ◽  
In Vitro Experiments ◽  
Chemical Modifications ◽  
Pharmacokinetic Properties ◽  
Target Binding ◽  
The Individual

Abstract The introduction of non-bridging phosphorothioate (PS) linkages in oligonucleotides has been instrumental for the development of RNA therapeutics and antisense oligonucleotides. This modification offers significantly increased metabolic stability as well as improved pharmacokinetic properties. However, due to the chiral nature of the phosphorothioate, every PS group doubles the amount of possible stereoisomers. Thus PS oligonucleotides are generally obtained as an inseparable mixture of a multitude of diastereoisomeric compounds. Herein, we describe the introduction of non-chiral 3′ thiophosphate linkages into antisense oligonucleotides and report their in vitro as well as in vivo activity. The obtained results are carefully investigated for the individual parameters contributing to antisense activity of 3′ and 5′ thiophosphate modified oligonucleotides (target binding, RNase H recruitment, nuclease stability). We conclude that nuclease stability is the major challenge for this approach. These results highlight the importance of selecting meaningful in vitro experiments particularly when examining hitherto unexplored chemical modifications.

Biodegradable Microfluidic Scaffolds with Tunable Degradation Properties from Amino Alcohol-based Poly(ester amide) Elastomers

2011 ◽  
Vol 1299 ◽  
Author(s):  
Jane Wang ◽  
Tatiana Kniazeva ◽  
Carly F. Campbell ◽  
Robert Langer ◽  
Jeffrey S. Ustin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Biodegradable Polymers ◽  
Half Life ◽  
Microfluidic Devices ◽  
Gas Permeation ◽  
Microfluidic Channels ◽  
Tissue Engineering Scaffolds ◽  
Rapid Prototyping And Manufacturing ◽  
Degradation Properties

ABSTRACTBiodegradable polymers with high mechanical strength, flexibility and optical transparency, optimal degradation properties and biocompatibility are critical to the success of tissue engineered devices and drug delivery systems. In this work, microfluidic devices have been fabricated from elastomeric scaffolds with tunable degradation properties for applications in tissue engineering and regenerative medicine. Most biodegradable polymers suffer from short half life resulting from rapid and poorly controlled degradation upon implantation, exceedingly high stiffness, and limited compatibility with chemical functionalization. Here we report the first microfluidic devices constructed from a recently developed class of biodegradable elastomeric poly(ester amide)s, poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s (APS), showing a much longer and highly tunable in vivo degradation half-life comparing to many other commonly used biodegradable polymers. The device is molded in a similar approach to that reported previously for conventional biodegradable polymers, and the bonded microfluidic channels are shown to be capable of supporting physiologic levels of flow and pressure. The device has been tested for degradation rate and gas permeation properties in order to predict performance in the implantation environment. This device is high resolution and fully biodegradable; the fabrication process is fast, inexpensive, reproducible, and scalable, making it the approach ideal for both rapid prototyping and manufacturing of tissue engineering scaffolds and vasculature and tissue and organ replacements.

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