-
Advanced Healthcare Materials Sep 2022With the rapid growth of fungal infections and the emergence of multi-drug resistant (MDR) fungal strains, new antifungals with novel mechanisms are a pressing need to...
With the rapid growth of fungal infections and the emergence of multi-drug resistant (MDR) fungal strains, new antifungals with novel mechanisms are a pressing need to tackle this emerging health problem. Herein it is reported for the first time that hyperbranched polylysine (HPL) shows antifungal activities against Candida, especially for drug-sensitive and MDR C. albicans strains, and broad-spectrum antibacterial activities against both Gram-negative and Gram-positive bacteria. The high antimicrobial activities are ascribed to the high charge density and compact size of the globular structure of HPL. The in vitro antifungal activities of HPL3 are further enhanced by the modification of amine groups to form guanylated polylysines (HPL3-Gxs). Similar to antimicrobial peptides (AMPs), HPLs and HPL3-Gxs interact with and lyse the membranes of microbes, which mitigates the emergence of drug resistance. HPLs and HPL3-Gxs demonstrate excellent in vivo antimicrobial efficacies against both lethal C. albicans challenge in the invasive candidiasis model and lethal Methicillin resistant Staphylococcus aureus challenge in the peritonitis model, and have potentials as broad-spectrum antimicrobials.
Topics: Amines; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Candida albicans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Polylysine
PubMed: 35775877
DOI: 10.1002/adhm.202201091 -
Biomaterials Science Nov 2023Invasive fungal infections pose a crucial threat to public health and are an under-recognized component of antimicrobial resistance, which is an emerging crisis...
Invasive fungal infections pose a crucial threat to public health and are an under-recognized component of antimicrobial resistance, which is an emerging crisis worldwide. Here we designed and synthesized a panel of multi-arm ε-polylysines (ε-mPLs, R-K) with a precise number of = 3-6 arms of ε-oligo(L-lysine)s and a precise arm length of = 3-7 ε-lysine residues. ε-mPLs have good biocompatibility and exhibited broad-spectrum antifungal activities towards , and species, and their antifungal activities increased with residue arm length. Among these ε-mPLs, 3R-K7 showed high antifungal activity against with a MIC value of as low as 24 μg mL (only 1/16th that of ε-PL) and also exhibited similar antifungal activity towards the clinically isolated multi-drug resistant (MDR) strain. Furthermore, 3R-K7 could inhibit the formation of biofilms and kill the cells within mature biofilms. Mechanistic studies proved that 3R-K7 killed fungal cells by entering the cells to generate reactive oxygen species (ROS) and induce cell apoptosis. An study showed that 3R-K7 significantly increased the survival rate of mice in a systemic murine candidiasis model, demonstrating that ε-mPL has great potential as a new antifungal agent.
Topics: Animals; Mice; Antifungal Agents; Candida; Polylysine; Candidiasis; Candida albicans; Microbial Sensitivity Tests; Biofilms
PubMed: 37823351
DOI: 10.1039/d3bm01233f -
Biomedicine & Pharmacotherapy =... Jun 2023Drug delivery systems require that carrier materials have good biocompatibility, degradability, and constructability. Poly(amino acids), a substance with a distinctive...
Drug delivery systems require that carrier materials have good biocompatibility, degradability, and constructability. Poly(amino acids), a substance with a distinctive secondary structure, not only have the basic features of the carrier materials but also have several reactive functional groups in the side chain, which can be employed as drug carriers to deliver anticancer drugs. The conformation of isomers of drug carriers has some influence on the preparation, morphology, and efficacy of nanoparticles. In this study, two isomers of polylysine, including ε-polylysine (ε-PL) and α-polylysine (α-PL), were used as drug carriers to entrap methotrexate (MTX) and construct nano-drug delivery systems. ε-PL/MTX nanoparticles with the morphology of helical nanorods presented a small particle size (115.0 nm), and relative high drug loading content (57.8 %). The anticancer effect of ε-PL/MTX nanoparticles was 1.3-fold and 2.6-fold stronger than that of α-PL/MTX nanoparticles in vivo and in vitro, respectively. ε-PL is an ideal drug carrier with potential clinical application prospects.
Topics: Methotrexate; Polylysine; Antineoplastic Agents; Drug Carriers; Nanoparticles
PubMed: 37037095
DOI: 10.1016/j.biopha.2023.114662 -
Reproduction in Domestic Animals =... Jul 2023Carboxylated poly-l-lysine (CPLL) is an anti-freeze agent having pronounced non-permeating yet membrane stabilizing cryoprotective capabilities. The objective was to...
Carboxylated poly-l-lysine (CPLL) is an anti-freeze agent having pronounced non-permeating yet membrane stabilizing cryoprotective capabilities. The objective was to evaluate the CPLL supplementation in extender in terms of post-thaw quality (sperm), total anti-oxidant activity (milt) and fertilization potential of cryopreserved Labeo rohita sperm. For this purpose, male brood fish reared at a fish seed hatchery, Rawal Town Islamabad, Pakistan were captured from different rearing ponds and acclimatized in hatchery ponds for 6 h. The brooder was injected with Ovaprim (0.2 mL/kg), and milt was collected after 8 h in cooled sterilized falcon tubes, maintained at 4°C and evaluated for sperm motility. The milt collected from three brooders (n = 3) was diluted in extenders viz., modified Kurokura-2 extender having 10% methanol (control); experimental extenders with CPLL supplementation at the rate of 0.5%, 1% and 1.5%. Diluted milt was filled in 0.5 mL straws, exposed to liquid nitrogen vapours and cryopreserved. Cryopreserved milt was thawed at 25°C and assessed for post-thaw sperm quality. Sperm motility, motility duration, viability, total anti-oxidant capacity and DNA integrity was significantly higher (p < 0.05) in the extender having 1.5% CPLL than control. To evaluate the fertilization rates, male and female brooders were injected with Ovaprim at 0.2 mL/Kg and 0.5 mL/Kg body weight respectively. Fresh eggs and milt were collected through abdominal stripping. Batches of 10 g of eggs from each female (n = 2) were fertilized with one straw, each from frozen sperm with KE + methanol (control), KE + methanol + 1.5% CPLL and 50 μL fresh milt (negative control). After 1.5 h of fertilization, eggs were collected from all jars and a total of 200 eggs were counted. The fertilized eggs appeared clear and transparent while unfertilized eggs looked opaque with disintegrated nuclei. Sperm fertilization rate (%) was higher (p < 0.05) in extender KE + methanol + 1.5% CPLL (78.7 ± 0.5) compared to control (KE + methanol) (52.0 ± 0.4) however, it was lower compared to that of negative control, the fresh milt (85.2 ± 0.6). In conclusion, supplementation of carboxylated poly-l-lysine (1.5%) to modified Kurokura-2 extender having 10% methanol improves post-thaw motility, motility duration, viability, DNA integrity, anti-oxidant capacity (milt) and fertilizing ability of cryopreserved L. rohita sperm.
Topics: Male; Female; Animals; Polylysine; Sperm Motility; Methanol; Antioxidants; Semen Preservation; Cryoprotective Agents; Seeds; Spermatozoa; Cryopreservation
PubMed: 37191551
DOI: 10.1111/rda.14391 -
Food Chemistry Oct 2023PVA/CC/CUR/PL composite films containing curcumin (CUR) and ε-polylysine (PL) were prepared by casting and chemical grafting methods to address the threat to food...
PVA/CC/CUR/PL composite films containing curcumin (CUR) and ε-polylysine (PL) were prepared by casting and chemical grafting methods to address the threat to food spoilage. Morphological analysis showed that the grafting of CUR and PL resulted in a rough cross-section of the polymer matrix. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the grafting of CUR and PL into the polymer matrix via esterification and amidation reactions, respectively. Thermal weight loss analysis showed that grafting process positively improved the thermal stability. The PVA/CC/CUR/PL films exhibited strong bactericidal activity, reaching 99.0% and 99.8% for Pseudomonas lundensis and Shewanella putrefaciens, respectively. After 8 days of storage, the total number of colonies and the TVB-N content in the PVA/CC/CUR/PL group decreased by 1.51 lg CFU/g and 13.77 mg/100 g, respectively. Therefore, PVA/CC/CUR/PL films are considered as a promising bactericidal material with good mechanical properties, functionality, and other excellent characteristics.
Topics: Animals; Polylysine; Cellulose; Curcumin; Chickens; Hydrogels; Anti-Bacterial Agents
PubMed: 37224635
DOI: 10.1016/j.foodchem.2023.136345 -
International Journal of Biological... Nov 2022The effects of ε-polylysine (ε-PL) at different concentrations (0.005 %, 0.010 %, 0.020 %, and 0.030 %) on the structure and gelling behavior of pork myofibrillar...
The effects of ε-polylysine (ε-PL) at different concentrations (0.005 %, 0.010 %, 0.020 %, and 0.030 %) on the structure and gelling behavior of pork myofibrillar protein (MP) under oxidative stress were explored. The incorporation of ε-PL significantly restrained oxidation-induced sulfhydryl and solubility losses (up to 9.72 % and 41.9 %, respectively) as well as protein crosslinking and aggregation. Compared with the oxidized control, ε-PL at low concentrations (0.005 % - 0.020 %) promoted further unfolding and destabilization of MP, while 0.030 % ε-PL led to refolding of MP and enhanced its thermal stability. The ε-PL-induced physicochemical changes favored the formation of a finer and more homogeneous three-dimensional network structure, therefore obviously enhancing the strength and water-holding capacity (WHC) of thermally induced oxidized MP gels, with the ε-PL at 0.020 % showed the greatest enhancement. This work revealed for the first time that ε-PL can significantly ameliorate the oxidation stability and gel-forming ability of meat proteins.
Topics: Gels; Meat Proteins; Muscle Proteins; Myofibrils; Oxidative Stress; Polylysine; Water
PubMed: 36030980
DOI: 10.1016/j.ijbiomac.2022.08.143 -
International Journal of Biological... Dec 2022Food preservation using biopreservative agents mainly microbial based metabolites have gained more attention in the modern food sector due to their broad spectrum... (Review)
Review
Food preservation using biopreservative agents mainly microbial based metabolites have gained more attention in the modern food sector due to their broad spectrum anti-microbial efficacy with high biocompatibility. However, the effectiveness of these biopreservatives is highly dependent on suitable formulation which will enhance the desired efficacy without affecting the nutritional value of the foods. Polylysine-actinomycete derived anti-microbial metabolite is used as biopreservative agent in various food products. This review provides a valuable insight into the formulation of polylysine with nanotechnology principles for enhanced antimicrobial efficacy against food spoilage organisms. This review highlighted the diverse methods of polylysine nanoformulation preparation. Formulation of polylysine as functionalised nanomaterials can be prepared via green science or green technology principles was extensively studied in this review. This study also revealed the methods for the determination of anti-microbial assays and biocompatibility tests in vitro and in vivo biocompatibility tests. Future prospects of nanoformulated polylysine in bio preservation can be extended to safe processing of canned and ready-to-eat food products without affecting the nutritional value of the foods.
Topics: Polylysine; Antimicrobial Cationic Peptides; Antimicrobial Peptides; Food Preservation; Nanotechnology
PubMed: 36206840
DOI: 10.1016/j.ijbiomac.2022.09.238 -
Colloids and Surfaces. B, Biointerfaces Aug 2017Thin films mimicking the structure and composition of the extra-cellular matrix (ECM) are potentially attractive as biomaterials for cell contacting applications....
Thin films mimicking the structure and composition of the extra-cellular matrix (ECM) are potentially attractive as biomaterials for cell contacting applications. Layer-by-layer (LbL) assembly of a biological polycation, poly(l-lysine) (PLL), and a common ECM protein, fibronectin (Fn), was employed here to construct nanoscale, ECM mimicking films. Incremental film thickness and interfacial charge magnitude are observed to diminish with layer number, resulting in sub-linear film growth scaling and saturation after about 10 layers. Infrared spectroscopy and electron microscopy together reveal the formation of Fn containing aggregates, whose presence correlates with diminished charge reversal and suppressed LbL assembly. PLL-Fn films induce a significantly greater murine MC3T3-E1 pre-osteoblastic cell proliferation, while maintaining a much higher proportion of Fn in the molecular (as opposed to fibrillar) state, compared to a Fn monolayer, suggesting the enhanced Fn content of these ECM-mimicking films to significantly, and positively, affect cell behavior.
Topics: 3T3 Cells; Animals; Cell Adhesion; Cell Proliferation; Fibronectins; Mice; Polylysine
PubMed: 28544963
DOI: 10.1016/j.colsurfb.2017.05.023 -
Journal of Materials Chemistry. B Oct 2023Uncontrollable bleeding is a crucial factor that can lead to fatality. Therefore, the development of hemostatic dressings that enable rapid hemostasis is of utmost...
Uncontrollable bleeding is a crucial factor that can lead to fatality. Therefore, the development of hemostatic dressings that enable rapid hemostasis is of utmost importance. Hydrogels with injectability, self-healing ability, and adhesiveness hold significant potential as effective hemostatic dressings. Herein, a composite hydrogel was fabricated by the oxidized Konjac glucomannan and ε-polylysine. After the encapsulation of a hemostatic drug, etamsylate, an oxidized Konjac glucomannan/ε-polylysine/etamsylate (OKGM/PL/E) composite hydrogel that possesses favorable properties including injectability, self-healing ability, tissue adhesiveness, hemocompatibility and cytocompatibility was fabricated. The OKGM/PL/E hydrogel demonstrated the ability to effectively adhere red blood cells and seal wounds, enabling rapid control of hemorrhaging. wound healing experiments confirmed the hemostatic and wound healing efficacy of the OKGM/PL/E hydrogel, highlighting its potential as a valuable hemostatic dressing.
Topics: Ethamsylate; Polylysine; Chitosan; Hydrogels; Wound Healing; Hemostasis; Hemostatics
PubMed: 37830374
DOI: 10.1039/d3tb01904g -
ACS Applied Bio Materials Apr 2022Brain tissues demonstrate heterogeneous mechanical properties, which evolve with aging and pathologies. The observation in these tissues of smooth to sharp rigidity...
Brain tissues demonstrate heterogeneous mechanical properties, which evolve with aging and pathologies. The observation in these tissues of smooth to sharp rigidity gradients raises the question of brain cell responses to both different values of rigidity and their spatial variations, in dependence on the surface chemistry they are exposed to. Here, we used recent techniques of hydrogel photopolymerization to achieve stiffness texturing down to micrometer resolution in polyacrylamide hydrogels. We investigated primary neuron adhesion and orientation as well as glial cell proliferative properties on these rigidity-textured hydrogels for two adhesive coatings: fibronectin or poly-l-lysine/laminin. Our main observation is that glial cell adhesion and proliferation is favored on the stiffer regions when the adhesive coating is fibronectin and on the softer ones when it consists of poly-l-lysine/laminin. This behavior was unchanged by the presence or the absence of neuronal cells. In addition, glial cells were not confined by sharp, micron-scaled gradients of rigidity. Our observations suggest that rigidity sensing could involve adhesion-related pathways that profoundly depend on surface chemistry.
Topics: Adhesives; Fibronectins; Hydrogels; Laminin; Neuroglia; Polylysine
PubMed: 35274925
DOI: 10.1021/acsabm.1c01295