Burn injury treatment is usually accompanied by significant challenges, such as microbial growth and chronic inflammation. A multifunctional nanofibrous dressing with biphasic chemical properties is fabricated to regulate infection and inflammation in infected burns simultaneously. Hydrophobic polymer polycaprolactone (PCL) and hydrophilic polymer chitosan (CS) were used to fabricate a core-shell nanofibrous dressing that encapsulates the anti-inflammatory drug flurbiprofen (FLB) and the antibacterial drug ciprofloxacin (CIP). The dressings PCL-CS/FLB-CIP were characterized using TEM, FESEM, contact angle measurements, and FTIR spectroscopy. The phase boundaries in the fibers result in controlled release of both drugs, i.e., 70 h and 80 h, CIP and FLB, respectively, in vitro. The dressings exhibited significant ROS scavenging activity and in vitro biocompatibility over NHDF cells, with good cell adhesion for up to 7 days. The in vitro antibacterial properties exhibited maximum inhibition at 50-60 h against Staphylococcus aureus and Escherichia coli. Furthermore, the effect of FLB release showed immunomodulatory efficacy of the dressings when determined against macrophage-like THP-1 cells. Furthermore, the in vivo healing potential of the dressings was determined over infected burns with Staphylococcus aureus in BALB/c mice and this group showed significant healing on day 18 compared to the untreated group. Bacterial growth inhibition, re-epithelization, neovascularization, collagen reappearance, and orientation were determined using the colony count method, and H&E, MT, and VG staining, respectively. Also, evidence from IHC staining confirmed secondary skin organ formation. The PCL-CS-based dual drug delivery system provides synergistic enhanced therapeutic efficacy and could be a solution to the simultaneous challenges in burn wounds.

Emergence of antimicrobial resistance in enteric bacterial pathogens towards conventional antibiotics is a serious concern worldwide. Antimicrobial peptides (AMPs) are touted to be reliable future antibiotics. However, oral delivery of AMPs for localized therapy of enteric diseases such as Enterotoxigenic Escherichia coli (ETEC) infection, is still a formidable challenge. Thus, the present study was aimed at preparation, biophysical characterization, and in vitro/in vivo therapeutic efficacy determination of a multiparticulate oral formulation (NMF) encapsulating nisin to treat ETEC induced diarrhea. Results: indicated that microencapsulation technology could successfully form NMF which comprised of spheroidal nanoparticles-in-microcapsules (similar to 2-4 mu m). Each particle consisted of nisin-loaded selenium nanoparticles (Ni similar to SeNPs) in the core encapsulated within pectin shell. 100 mg dry weight of pectin microcapsules was composed of nisin similar to 1000 IU and nanoselenium similar to 250 ppm, and showed encapsulation efficiency of 87.68 +/- 0.7 %. It exhibited nearly 2-fold enhanced antibacterial activity against ETEC as compared to free nisin in vitro (MIC value for NMF = 125 +/- 5 mu g/mL; free nisin at 203 +/- 5 mu g/mL). Moreover, oral administration of NMF had significant anti-bacterial efficacy against ETEC bacteria in vivo as confirmed by reduction in each of diarrhea score, bacterial load etc.; restoration of histopathological damage and tissue injury markers. Cellular membrane disruption was found to be the primary mode of bacterial lysis as shown by AO/PI, Flow cytometry and FESEM studies. Conclusively: NMF has been able to encapsulate nisin, and enhanced its oral therapeutic use as evaluated in a ratETEC infection model.

The existing treatment approaches against urinary tract infections (UTIs) are associated with severe side effects and antimicrobial resistance. Human defensin-5 (HD-5) is an important component of the innate defense mechanism in the urinary tract. The aim of our study was to evaluate the antimicrobial potential of intravesically administered HD-5 against uropathogenic Escherichia coli (UPEC) in rat cystitis model. To the best of our knowledge, this is the first study to demonstrate the therapeutic role of exogenously administered HD-5, in UTIs. With an MIC of 60 µg/ml against UPEC, HD-5 exerted antimicrobial activity primarily by disrupting membrane integrity, leading to blebbing, release of extracellular contents, and ultimately whole-cell lysis. HD-5 administered via the intravesical route significantly reduced UPEC load by 54

Breast cancer is a highly lethal disease with significant mortality and it’s the need of the hour to develop therapies that can effectively target the cancer tissues and increase the survival rates of patients. Sorafenib (SFB) is a multi-kinase inhibitor possesses anticancer efficacy. However, its pharmacological activities are limited due to its poor solubility and less bioavailability. To overcome these drawbacks and increase its anticancer efficacy, the exosomes formulation loaded with SFB (SFB-EXO) are developed. The exosomes are isolated from the fresh cow milk using ultracentrifugation method and loaded with SFB using ultrasonication. The size of the exosomes is near to 100 nm with spherical shape. The exosomes have showed sustained release profile for oral delivery in simulated gastrointestinal fluid. The various in-vitro cell culture assays of MDA-MB-231 and MCF-7 breast cancer cell lines indicating that SFB-EXO exhibits enhance anticancer activity including high cellular uptake, cytotoxicity, apoptosis and increase reactive oxygen species (ROS) generation. Additionally, the evidence from in-vivo pharmacokinetic studies also supports the improvement in oral bioavailability and other pharmacokinetic parameters of SFB after loading into the exosomes. This study successfully establishes an exosomal drug delivery carrier that significantly improves the targeting and therapeutic efficacy of SFB against breast cancer imparting a novel strategy for the targeted breast cancer therapy.

The therapeutic efficacy of cisplatin is limited by systemic toxicity, acquired resistance, and poor cancer cell specificity. To address these limitations, we developed solid lipid nanocarriers for the co-delivery of nisin and cisplatin (Nis + Cis-SLNs). The developed SLNs exhibited monodisperse spherical morphology, high encapsulation efficiency and sustained release. The therapeutic potential of Nis + Cis-SLNs was evaluated against epithelial malignancies using human epidermoid carcinoma (A431) and breast adenocarcinoma (MCF-7) cells. The nanocarriers demonstrated enhanced cytotoxicity compared to free nisin and cisplatin by synergistically targeting proliferation, apoptosis, and reactive oxygen species generation. Nis + Cis-SLNs triggered an intrinsic apoptotic response by upregulation of caspase-3, Bax, and suppression of Bcl-2. Beyond direct cytotoxicity, conditioned media derived from Nis + Cis-SLNs treated tumor cells were associated with reduced M2 macrophage polarization, suggesting a possible role in immunomodulation of the tumor microenvironment. Collectively, these findings highlight the potential of Nis + Cis-SLNs as a promising co-delivery strategy to enhance cisplatin efficacy at reduced doses, potentially improving therapeutic outcomes.

Healing wounds is no longer a passive process but a dynamic interplay between advanced materials, therapeutic agents and innovative technologies. Chronic wounds, aggravated by factors like diabetes, aging and multidrug-resistant infections, demand solutions beyond traditional dressings. Advanced wound care has evolved into an active therapeutic strategy, leveraging biomaterials that mimic the extracellular matrix, foster tissue regeneration and combat infections. Recent advances in fabrication techniques, such as three-dimensional bioprinting, electrospinning and microfluidic templating, have enabled precise customization of wound dressings tailored to complex clinical challenges. The integration of bioactive molecules and growth factors, further enhances the efficacy of these dressings. Emerging trends like bioengineered hydrogels and real-time monitoring systems have the potential to transform wound care into an intelligent, adaptive process that responds to patient-specific needs. By addressing the current challenges and exploring emerging biomaterials, a future with personalized scar-free wound healing technologies may be achieved in the future. The current article begins by providing an overview of skin, wounds and the factors responsible for delaying wound healing. With this background, the traditional and advanced biomaterial based wound care strategies have been discussed extensively. The main focus is to present a comprehensive account on the integrated approaches in advance wound care management, combining breakthroughs in material science, biotechnology and clinical innovations to revolutionize the field of wound healing. This review promises a one-stop exhaustive report that shall be the torchbearer for future research endeavours in the field of wound care and management.

Current treatment strategies for Pseudomonas aeruginosa pulmonary infections are limited by severe side effects and the emergence of multidrug resistance. This study evaluated the therapeutic potential of nisin and lactoferrin, two antimicrobial peptides with distinct modes of action, against P. aeruginosa lung infections. In vitro, the combination exhibited potent synergistic antibacterial activity with significant suppression of biofilm formation and pyocyanin production. Morphological analysis by field-emission scanning electron microscopy revealed extensive structural disruption of bacterial cells exposed to the nisin/lactoferrin combination. In a rat model of pulmonary P. aeruginosa infection, co-administration of nisin and lactoferrin prevented weight loss, preserved lung architecture, and achieved 100% survival compared with untreated animals. Treatment significantly reduced bacterial burden in the lungs and trachea, restored cytokine balance, enhanced antioxidant defenses, and lowered oxidative stress. These findings highlight the nisin/lactoferrin combination as a safe and effective peptide-based therapeutic approach for multidrug-resistant P. aeruginosa lung infections.

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14

Background and AimThe increasing dilemma of multidrug-resistant cancer cells in response to currently available chemotherapeutic drugs and their associated side effect(s), calls for the investigation of alternative anticancer advances and molecules. Therefore, the present study aimed to elucidate the combinatorial potential against colon cancer of human defensin 5 in combination with 5-fluorouracil (5-FU), and against 5-FU resistant colon tumor cells.MethodsThe in vivo combinatorial potential of HD-5 with 5-FU was elucidated in terms of tumor morphometrics, apoptosis assay, surface morphology histology of the colon(s), and transcriptional alterations. Changes in membrane dynamics with mucin expression were evaluated by fluorescence microscopy and histochemistry. The in vitro activity of the peptide/drug conjunction was explored by phase contrast microscopy, MTT, LDH assay, and AO/EtBr staining. Chemoresistance to 5-FU was determined by phase contrast microscopy, MTT assay, annexin V-FITC/PI flow cytometry, and MDR-1, Bak, and Bax expression.ResultsIn vivo decreases in tumor parameters, with a marked increase in apoptosis and neutrophil infiltrations indicated restoration of normal architecture with improved mucin content in the treated colons. This happened with substantial changes in key molecular markers of the intrinsic apoptotic cascade. Membrane dynamics revealed that peptides and chemotherapeutic drugs could bind to cancerous cells by taking advantage of altered levels of membrane fluidity.ConclusionPeptide treatment of drug-resistant Caco-2 cells promotes enhanced 5-FU uptake, in contrast to when cells were treated with 5-FU alone. Hence, HD-5 as an adjunct to 5-FU, exhibited strong cancer cell killing even against 5-FU-resistant tumorigenic cells.

Tungsten oxide/molybdenum oxide nanocomposites have been synthesized using a cost-effective internal combustion method by incorporating two different phases of tungsten oxide into hexagonal and orthorhombic molybdenum oxide nanostructures. The synthesized materials were subjected to different analytical techniques, including X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy, to investigate their structural and morphological properties. The synthesized materials were employed for the adsorption of methylene blue by varying different parameters, such as the initial dye concentration, contact time, adsorbent dose, pH, and temperature of the solution. The thermodynamical parameters were calculated to validate the adsorption phenomenon in terms of its spontaneity and feasibility. Various kinetic studies, such as pseudo-first-order, pseudo-second-order, and intra-particle diffusion models, were used to determine kinetic parameters and understand the adsorbate-adsorbent interactions. The detailed characteristics of adsorbent surface and adsorption behavior were studied using the Langmuir, Freundlich, and Temkin isotherms. Among these, monoclinic tungsten oxide/orthorhombic molybdenum oxide exhibits the best adsorption efficiency and higher kinetic rate constant, followed by the orthorhombic tungsten oxide/orthorhombic molybdenum oxide nanocomposite. Dye adsorption over the adsorbent surface was confirmed by investigating the materials characteristics before and after the process using Fourier infrared transform spectroscopy. The enhanced adsorption efficiency and higher rate constant can be attributed to the improved surface properties of these materials.

In recent years, the occurrence of a wide variety of drug-resistant diseases has led to an increase in interest in alternate therapies. Peptide-based drugs as an alternate therapy hold researchers' attention in various therapeutic fields such as neurology, dermatology, oncology, metabolic diseases, etc. Previously, they had been overlooked by pharmaceutical companies due to certain limitations such as proteolytic degradation, poor membrane permeability, low oral bioavailability, shorter half-life, and poor target specificity. Over the last two decades, these limitations have been countered by introducing various modification strategies such as backbone and side-chain modifications, amino acid substitution, etc. which improve their functionality. This has led to a substantial interest of researchers and pharmaceutical companies, moving the next generation of these therapeutics from fundamental research to the market. Various chemical and computational approaches are aiding the production of more stable and long-lasting peptides guiding the formulation of novel and advanced therapeutic agents. However, there is not a single article that talks about various peptide design approaches i.e., in-silico and in-vitro along with their applications and strategies to improve their efficacy. In this review, we try to bring different aspects of peptide-based therapeutics under one article with a clear focus to cover the missing links in the literature. This review draws emphasis on various in-silico approaches and modification-based peptide design strategies. It also highlights the recent progress made in peptide delivery methods important for their enhanced clinical efficacy. The article would provide a bird's-eye view to researchers aiming to develop peptides with therapeutic applications.

Methotrexate (MTX) has shown remarkable therapeutic effects against a variety of cancers. However, it is related to various challenges like dose-influenced side effects, compromised bioavailability, and poor tissue penetration. Henceforth, a poly-(lactic-co-glycolic acid) (PLGA)-based D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) conjugated MTX self-assembled nanoparticulate system was developed. The synthesized conjugate (MTX-PLGA-TPGS) was affirmed by FT-IR and NMR spectroscopy, and the developed self-assembled nanoparticles were characterized for particle size, zeta potential, surface charge, drug loading and drug entrapment. The evaluation studies included drug release at the plasma and cancer cell pH, compatibility with erythrocytes, plasma protein binding, in-vitro cytotoxicity on cancer cell lines, confocal laser scanning microscopy, and in-vivo pharmacoki-netics. The FT-IR and 1H NMR confirmed the successful conjugation of the two macromolecules. The developed nanoparticulate system offered controlled drug release in a pH-dependent manner, releasing the maximum drug at the pH of cancer cells. The developed systems were not only found to be biocompatible with erythrocytes but also offered substantially enhanced cytotoxicity on MDA-MB-231 cells. The confocal laser scanning microscopy confirmed higher cellular uptake and pharmacokinetics in rodents offered markedly elevated AUC and sub-stantially retarded elimination from the central compartment. The findings vouch for the immense promise of the designed nanosystem in enhancing the efficacy, permeation, safety and reducing the dose and dosing frequency of a well-established BCS class IV drug candidate.

AimThe present study aimed to develop topical combinatorial therapy of nisin and 5-fluorouracil in a single nanosized formulation against skin cancer.MethodsNisin and 5-fluorouracil were encapsulated in an organogel system (NF-OG) and investigated for morphology, physicochemical properties, cytotoxicity, encapsulation and release. NF-OG was evaluated against DMBA/TPA murine skin cancer in terms of tumour statistics, histoarchitecture, TUNEL and M1/M2 macrophages.ResultsThe optimised NF-OG formulation exhibited particle size of 185.1 +/- 11.24 nm, zeta potential of -7.93 +/- 0.60 mV, offered substantial drug loading and temporal release. NF-OG therapy led to improved cytotoxicity of nisin and 5-FU against B16-F10 cells, significant decrease in tumour volume (84.983 mm(3)) in treated group as compared to untreated group (490.482 mm(3)) accompanied by restoration of histoarchitecture and repolarization of macrophages.ConclusionThe study yielded a promising delivery system exhibiting potent anticancer activity and forms the bases for further applications in clinical settings.

About twenty percent of diabetic patients develop diabetic wounds and diabetic foot gradually resulting in severe infections and lower limb complications. Antimicrobial peptides (AMPs) are potential candidates exploited for their wound healing properties. Nisin a class I bacteriocin having GRAS (Generally recognized as safe) status has been demonstrated to have wound healing effects. We established a diabetic wound excision model in rats via streptozotocin administration and evaluated the efficacy of nisin in pacing up wound healing in terms of wound closure parameters, collagen content, histopathological and topographical alterations, oxidant and antioxidative environment of wounded tissue, cytokines and growth factors expressions. Significant increase in the levels of hydroxyproline, hexosamine and hexuronic acid upon nisin therapy directly pointed towards the increased collagen content. Significant alterations in wound diameter, levels of IL-1, IL-6, TNF-α and transcriptional levels of VEGF and EGF were observed in treated rats. H&E, picro-sirius red staining and scanning electron micrographic studies of treated skin tissues revealed the restoration of different layers of skin tissue along with increase in collagen content and skin regeneration. Biochemical parameters indicated increase in levels of antioxidants and reduced tlevels of free radicals upon therapy thereby improving the oxidative stress prevailing in wound microenvironment. The present study established nisin as a wound healing promoter in diabetes.

The emergence of multidrug resistance coupled with shrinking antibiotic pipelines has increased the demand of antimicrobials with novel mechanisms of action. Therefore, researchers across the globe are striving to develop new antimicrobial substances to alleviate the pressure on conventional antibiotic therapies. Host-Defence Peptides (HDPs) and their derivatives are emerging as effective therapeutic agents against microbial resistance. In this study, five analogs (DP1-5) of the N-terminal (N-15) fragment of CATH-2 were designed based on the delicate balance between various physicochemical properties such as charge, aliphatic character, amphipathicity and hydrophobicity. By means of in-silico and in-vitro studies a novel peptide (DP1) with the sequence "RFGRFLRKILRFLKK" was found to be more effective and less toxic than the N-terminal CATH-2 peptide. Circular dichroism spectroscopy and differential scanning calorimetry were applied for structural insights. Antimicrobial, haemolytic, and cytotoxic activities were also assessed. The resulting peptide was characterized by low cytotoxicity, low haemolytic activity, and efficient anti-microbial activity. Structurally, it displayed strong helical properties irrespective of the solvent environment and was stable in membrane-mimicking environments. Taken together, the data suggests that DP1 can be explored as a promising therapeutic agent with possible clinical applications.

Cancer is a major health concern worldwide as conventional treatment modalities face several limitations such as drug resistance, toxicity etc. To overcome such deficits, combination therapy involving anticancer peptides and chemodrugs is being considered as an attractive strategy. Therefore, present study developed, characterized and evaluated the anticancer potential of a single nanoconstruct comprising of oligomeric chitosan coated silver nanoparticles co-loaded with nisin and 5-florouracil (5-FU/nisin-CHI-AgNPs) against DMBA/TPA-induced murine skin cancer. It was fabricated using wet reduction method of silver salt to form silver nanoparticles followed sequentially by oligomeric chitosan coating, nisin conjugation to deacetylated units of chitosan oligomers (EDC/NHS chemistry) and physical loading of 5-FU. Biophysical characterisation studies revealed that the developed nanoconstruct had UV-visible absorption maxima at 420 nm, zeta potential of + 32.90 mV and 72.39 nm particle size (TEM analysis). In vivo anticancer therapeutic potential was assessed in terms of tumor statistics, histopathological, scanning electron microscopic analyses and testing oxidant/antioxidant status which exhibited marked reduction both in mean tumor volume (68.34 %) and mean tumor burden (82.39 %); restored skin histoarchitecture and improved oxidant/antioxidant status. Interestingly, anticancer therapeutic potential of nisin and 5-florouracil was found to be enhanced in vivo when bound on single composite nanoconstruct. The study forms a basis for developing synergetic single platforms against variety of cancers.