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Bioactive Materials Jul 2023Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid...
Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid hemostasis, inflammation regulation, and skin tissue remodeling into the one system instead of single-stage boosting. In this work, a multilayer-structured bioactive glass nanopowder (BGN@PTE) is developed by coating the poly-tannic acid and ε-polylysine onto the BGN facile layer-by-layer assembly as an integrative and multilevel dressing for the sequential management of wounds. In comparison to BGN and poly-tannic acid coated BGN, BGN@PTE exhibited the better hemostatic performance because of its multiple dependent approaches to induce the platelet adhesion/activation, red blood cells (RBCs) aggregation and fibrin network formation. Simultaneously, the bioactive ions from BGN facilitate the regulation of the inflammatory response while the poly-tannic acid and antibacterial ε-polylysine prevent the wound infection, promoting the wound healing during the inflammatory stage. In addition, BGN@PTE can serve as a reactive oxygen species scavenger, alleviate the oxidation stress in wound injury, induce the cell migration and angiogenesis, and promote the proliferation stage of wound repair. Therefore, BGN@PTE demonstrated the significantly higher wound repair capacity than the commercial bioglass dressing Dermlin™. This multifunctional BGN@PTE is a potentially valuable dressing for full-thickness wound management and may be expected to extend to the other wounds therapy.
PubMed: 36844363
DOI: 10.1016/j.bioactmat.2023.01.019 -
Biomimetics (Basel, Switzerland) Jan 2023Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from...
Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs' appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs' pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment.
PubMed: 36810381
DOI: 10.3390/biomimetics8010050 -
Nanotheranostics 2023Dendrigraft Poly-L-Lysine (d-PLL) coated gold nanoparticles (AuNPs) were synthesized by reducing Tetrachloroauric acid with ascorbic acid in the presence of d-PLL....
Dendrigraft Poly-L-Lysine (d-PLL) coated gold nanoparticles (AuNPs) were synthesized by reducing Tetrachloroauric acid with ascorbic acid in the presence of d-PLL. AuNPs-d-PLL formed a stable colloidal solution that absorbs light at a maximum wavelength (λ) centered at 570 nm as demonstrated by UV-visible (UV-Vis) spectroscopy. From Scanning Electron Microscopy (SEM) analysis, AuNPs-d-PLL were spherical in shape with a mean diameter of 128 ± 47 nm. Dynamic Light scattering (DLS) analysis of the colloidal solution exhibited one size distribution with a hydrodynamic diameter of about 131 nm (size distribution by intensity). Zeta potential (ξ) measurements revealed positively charged AuNPs-d-PLL with ξ about 32 mV, an indicator of high stability in an aqueous solution. The AuNPs-d-PLL was successfully modified with either thiolated poly (ethylene glycol) SH-PEG-OCH (M 5400 g mol) or folic acid-modified thiolated poly (ethylene glycol) SH-PEG-FA of similar molecular weight as demonstrated via DLS and Zeta potential measurements. Complexation of PEGylated AuNPs-d-PLL with siRNA was confirmed by DLS and gel electrophoresis. Finally, we analyzed the functionalization of our nanocomplexes with folic acid via targeted cellular uptake to prostate cancer cells using flow cytometry and LSM imaging. Our findings implicate the broader applicability of folate-PEGylated AuNPs in siRNA-based therapeutics against prostate cancer and perhaps other types of cancer.
Topics: Humans; Male; Polyethylene Glycols; Gold; Polylysine; RNA, Small Interfering; Folic Acid; Metal Nanoparticles; Prostatic Neoplasms
PubMed: 36793347
DOI: 10.7150/ntno.79050 -
Polymers Jan 2023This work presents the synthesis of a new representative of hemicurcuminoids with a nonyloxy substituent () as a fluorescent amphiphilic structural element of vesicular...
Supramolecular Optimization of Sensory Function of a Hemicurcuminoid through Its Incorporation into Phospholipid and Polymeric Polydiacetylenic Vesicles: Experimental and Computational Insight.
This work presents the synthesis of a new representative of hemicurcuminoids with a nonyloxy substituent () as a fluorescent amphiphilic structural element of vesicular aggregates based on phosphatidylcholine (PC), phosphatidylserine (PS), and 10,12-pentacosadiynoic acid (PCDA). Both X-ray diffraction analysis of the single crystal and H NMR spectra of in organic solvents indicate the predominance of the enol-tautomer of . DFT calculations show the predominance of the enol tautomer in supramolecular assemblies with PC, PS, and PCDA molecules. The results of the molecular modeling show that molecules are surrounded by PC and PS with a rather weak exposure to water molecules, while an exposure of molecules to water is enhanced under its supramolecular assembly with PCDA molecules. This is in good agreement with the higher loading of into PC(PS) vesicles compared to PCDA vesicles converted into polydiacetylene (PDA) ones by photopolymerization. molecules incorporated into -PDA vesicles exhibit greater planarity distortion and hydration effect in comparison with -PC(PS) ones. -PDA is presented as a dual fluorescence-chromatic nanosensor responsive to a change in pH within 7.5-9.5, heavy metal ions and polylysine, and the concentration-dependent fluorescent response is more sensitive than the chromatic one. Thus, the fluorescent response of -PDA allows for the distinguishing between Cd and Pb ions in the concentration range 0-0.01 mM, while the chromatic response allows for the selective sensing of Pb over Cd ions at their concentrations above 0.03 mM.
PubMed: 36772015
DOI: 10.3390/polym15030714 -
International Journal of Molecular... Feb 2023is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis (CF) or those hospitalized in intensive care...
is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis (CF) or those hospitalized in intensive care units. Given its remarkable ability to resist antibiotics, eradication has grown more challenging. Therefore, there is an urgent need to discover and develop new strategies that can counteract -resistant strains. Here, we evaluated the efficacy of poly-L-lysine (pLK) in combination with commonly used antibiotics as an alternative treatment option against . First, we demonstrated by scanning electron microscopy that pLK alters the integrity of the surface membrane of . We also showed using a fluorometry test that this results in an enhanced permeability of the bacteria membrane. Based on these data, we further evaluated the effect of the combinations of pLK with imipenem, ceftazidime, or aztreonam using the broth microdilution method in vitro. We found synergies in terms of bactericidal effects against either sensitive or resistant strains, with a reduction in bacterial growth (up to 5-log compared to the control). Similarly, these synergistic and bactericidal effects were confirmed ex vivo using a 3D model of human primary bronchial epithelial cells maintained in an air-liquid interface. In conclusion, pLK could be an innovative antipseudomonal molecule, opening its application as an adjuvant antibiotherapy against drug-resistant strains.
Topics: Humans; Pseudomonas aeruginosa; Polylysine; Pseudomonas Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 36769174
DOI: 10.3390/ijms24032851 -
International Journal of Molecular... Jan 2023In this article, we used the numerical self-consistent field method of Scheutjens-Fleer to study the micellization of hybrid molecules consisting of one polylysine...
In this article, we used the numerical self-consistent field method of Scheutjens-Fleer to study the micellization of hybrid molecules consisting of one polylysine dendron with charged end groups and several linear hydrophobic tails attached to its root. The main attention was paid to spherical micelles and the determination of the range of parameters at which they can appear. A relationship has been established between the size and internal structure of the resulting spherical micelles and the length and number of hydrophobic tails, as well as the number of dendron generations. It is shown that the splitting of the same number of hydrophobic monomers from one long tail into several short tails leads to a decrease in the aggregation number and, accordingly, the number of terminal charges in micelles. At the same time, it was shown that the surface area per dendron does not depend on the number of hydrophobic monomers or tails in the hybrid molecule. The relationship between the structure of hybrid molecules and the electrostatic properties of the resulting micelles has also been studied. It is found that the charge distribution in the corona depends on the number of dendron generations in the hybrid molecule. For a small number of generations (up to G=3), a standard double electric layer is observed. For a larger number of generations (G=4), the charges of dendrons in the corona are divided into two populations: in the first population, the charges are in the spherical layer near the boundary between the micelle core and shell, and in the second population, the charges are near the periphery of the spherical shell. As a result, a part of the counterions is localized in the wide region between them. These results are of potential interest for the use of spherical dendromicelles as nanocontainers for drug delivery.
Topics: Micelles; Dendrimers; Lysine; Anthracenes
PubMed: 36768408
DOI: 10.3390/ijms24032078 -
Foods (Basel, Switzerland) Jan 2023Coating preservation has a remarkable effect on the preservation of aquatic products. This work prepared a composite coating using konjac glucomannan (KGM) as the...
Effects of Konjac Glucomannan/ε-Polylysine Hydrochloride/Ferulic Acid Composite Coating on the Freshness Preservation Performance and Flavor of Refrigerated Sea Bass Fillets.
Coating preservation has a remarkable effect on the preservation of aquatic products. This work prepared a composite coating using konjac glucomannan (KGM) as the film-forming matrix and ε-polylysine hydrochloride (ε-PL) and ferulic acid (FA) as the preservative. Three types of treated sea bass (KGM, KGM-ε-PL, and KGM-ε-PL-FA) and untreated sea bass were stored at 4 °C for 20 days to compare freshness changes under different treatment conditions. The results showed that the surface color and texture of sea bass in refrigerated storage changed dramatically and deteriorated as storage time increased. The composite coating treatment was significantly different from the control group. Using Gas-phase ion migration spectrometry (GC-IMS) technology, 32 volatile compounds, such as aldehydes, alcohols, and ketones, were found in fillets during flavor quality analysis. The composite coating can successfully inhibit the formation of odor compounds such as 2-nonenone, isoamyl alcohol monomer, ammonia, and trimethylamine, delaying the deterioration of fish and improving freshness. Among them, KGM-ε-PL-FA composite coating has the most remarkable preservation performance, which significantly inhibits the occurrence of rotten odor, and has a potential application prospect in the field of food preservation.
PubMed: 36766047
DOI: 10.3390/foods12030517 -
Frontiers in Bioengineering and... 2022Wound repair remains a huge clinical challenge, which can cause bleeding, infection, and patient death. In our current research, a bioactive, injectable, multifunctional...
Wound repair remains a huge clinical challenge, which can cause bleeding, infection, and patient death. In our current research, a bioactive, injectable, multifunctional composite hydrogel doped with nanospheres was prepared with antibacterial and angiogenesis-promoting functions for the treatment of wounds. Amino groups in ε-polylysine (ε-EPL) undergo dynamic Schiff base reaction cross-linking with oxidized hyaluronic acid (OHA), and F127 exhibits unique temperature sensitivity to form an injectable thermosensitive hydrogel (FHE10), which can form a hydrogel to cover the wound at body temperature. Nanospheres (PNs) prepared using poly (glyceryl-sebacate-acrylate) (PGSA) were loaded into hydrogels (FHE10) for promoting wound repair. The prepared FHE10 exhibited rapid gelation, good injectable abilities, and showed resistance to the flourish of () and (). investigations showed that FHE10 had good hemocompatibility and cytocompatibility. FHE10@PNs exhibited good proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) and human foreskin fibroblasts (HFF-1). Furthermore, FHE10@PNs significantly promoted reepithelialization and collagen deposition as well as micro-vascularization compared with the use of FHE10 or PNs alone, thereby accelerating the repair of wounds. In general, this study demonstrated that the multifunctional injectable composite hydrogel showed great potential in wound treatment.
PubMed: 36714634
DOI: 10.3389/fbioe.2022.1091122 -
Cytotechnology Feb 2023β-lactoglobulin (BLG) and ε-polylysine (PL) were bound by using microbial transglutaminase. Dextran (Dex) was further conjugated to the BLG-PL conjugate by the...
β-lactoglobulin (BLG) and ε-polylysine (PL) were bound by using microbial transglutaminase. Dextran (Dex) was further conjugated to the BLG-PL conjugate by the Maillard reaction. Confirmation of conjugation was carried out by SDS-PAGE. From the results of isoelectric focusing, it was revealed that the isoelectric point of the BLG-PL conjugate was shifted to the basic side as compared with native BLG. Immunogenicity of BLG in BALB/c mice was lowered by conjugation with PL and further lowered by conjugation with Dex. By conjugation with PL and PL-Dex, antibacterial activity against was endowed to BLG. Because the conjugation method in this study is a safe method, it is valuable in that it can be applicable to food processing.
PubMed: 36713066
DOI: 10.1007/s10616-022-00558-8 -
Asian Journal of Pharmaceutical Sciences Jan 2023Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including...
Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy. This self-assembled micelle possesses the following essential components for CPT: (1) pH-sensitive PEG (OHC-PEG-CHO) for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles, which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake; (2) polypeptide polylysine-polyphenylalanine (PKF) synthesized ring-opening polymerization for micelle formation and CPT analogue loading; (3) dimeric CPT (DCPT) with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites. Interestingly, the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles. Also, the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation. In conclusion, this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.
PubMed: 36711109
DOI: 10.1016/j.ajps.2022.100773