Infected wound healing is delayed due to compromised immunity and antimicrobial resistance. Antibiotic resistance is an emerging threat due to the unnecessary use of antibiotics. Current wound dressings that promote chronic wound healing either require additional processes, such as photothermal irradiation, or leave behind large amounts of undesirable residues. Gramicidin D (GCN), a mixture of gramicidin A, B, and C derived from Bacillus brevis, is a linear antimicrobial peptide that has been shown to exhibit wound healing properties in recent studies. In silico molecular docking simulations of GCN were conducted to preliminarily explore its potential interactions with proteins associated with the wound-healing process. The analysis suggested possible binding interactions with MMP3 and MMP7, indicating a hypothetical mechanism that may warrant further experimental validation, rather than establishing a direct role in the observed wound-healing effects. Therefore, in this study, we report a dual-functionality chitosan (CS) hydrogel dressing enriched with GCN and a multifunctional, non-reducing carbohydrate moiety called trehalose (TH) for combating antimicrobial resistance and accelerating infected wound healing. The GCN- and TH-enriched hydrogel matrix was successfully developed using an ionic-crosslinking method and optimised with the Box-Behnken Design (BBD) approach using Design Expert Software. The developed hydrogel formulation demonstrated controlled GCN release, suitable physicochemical properties, and excellent antibacterial and antibiofilm potential. Moreover, the in vitro cell line data on HaCaT cells indicated suitable biocompatibility, non-toxic behaviour and enhanced cell migration. Additionally, an in vivo chronic infectious wound healing study confirmed that the GCN and TH dual-functional hydrogel promotes accelerated healing in rats. This approach represents a potential therapeutic strategy for the rapid healing of chronically infected wounds in a multifunctional manner.
Pullulan, a linear microbial α-glucan composed of maltotriose units linked by alternating α-(1 → 4) and α-(1 → 6) glycosidic bonds, has evolved from a food-grade excipient into a versatile platform for nanomedicine and regenerative biomaterials. This review synthesizes the structure-activity relationships (SAR) of pullulan and its derivatives, linking molecular design with macroscopic material performance and clinical potential across diverse biomedical applications. The presence of three hydroxyl groups per glucose unit (nine per maltotriose) enables diverse and site-specific chemical modifications, transforming an otherwise biologically inert backbone into highly functional and tunable biomaterials. Key strategies include cholesteryl grafting for self-assembling nanogels in cancer immunotherapy, periodate oxidation and methacrylation for dynamically crosslinked and 3D-printable hydrogels, and regioselective sulfation for heparin-mimetic anticoagulants. We also examine pullulan's intrinsic hepatotropism via the asialoglycoprotein receptor, enabling liver-targeted drug and gene delivery. Despite progress, including early-phase clinical evaluation of nanogel-based vaccines, broader pharmaceutical translation remains limited. Major challenges include poor mechanical strength of native networks (typically exhibiting a storage modulus (G') < 1 kPa), rapid enzymatic degradation, batch variability in molecular weight, and the lack of parenteral-grade regulatory standards. This review outlines future directions in precision modification, stimuli-responsive design, and standardization for clinical advancement and scalable biomedical applications.
Cystic fibrosis (CF) is a deadly and complicated lung disease, urgently required a novel approach of treatment. Drugs such as lumacaftor (LUM), modulators of cystic fibrosis transmembrane conductance regulator (CFTR), have showed promise in partially restoring chloride transport, but their poor bioavailability and systemic toxicity highlight the need for better ways to deliver. Poly (lactic-co-glycolic acid) (PLGA) is a biocompatible and biodegradable polymer; extensively utilized in nanoparticle-based drug delivery due to its capacity to facilitate controlled and prolonged release of drugs. Chitosan (CS) is a natural, biodegradable, and mucoadhesive polymer that enhances medication stability, enables controlled release, and fosters targeted administration by increasing cellular absorption and permeability across biological membranes. This study focuses on creating CS coated LUM-loaded PLGA nanoparticles (CS-LUM-PLGA-NPs); surface camouflaged with L-132 derived cell membrane (CM) denoted as CS-LUM-PLGA-NPs@CM for enhanced targeting, retention and restoration of CFTR protein synthesis. The extensive physicochemical studies showed that they are biocompatible, spherical and found within nano range (< 200 nm). The surface coating of CS and CM on LUM-PLGA-NPs was confirmed by Transmission electron microscopy (TEM). Additionally, in vitro studies indicated the non-toxicity and enhanced cellular internalization of CS-LUM-PLGA-NPs@CM nanocarrier in L-132 cells. The inhalable nanocarrier CS-LUM-PLGA-NPs@CM significantly decreased CF-related inflammation, excessive mucus production, and fibrosis with no significant toxicity on lung tissue. The extensive in vitro and in vivo results demonstrated that this novel therapeutic approach might serve as a promising strategy for CF therapy via biomimetic and multifunctional approach.
Transmucosal drug delivery presents a complex interfacial materials challenge where continuous mucus turnover, tight epithelial junctions, and dynamic fluid clearance fundamentally restrict therapeutic efficacy. Electrospun nanofibers have emerged as advanced polymeric platforms capable of overcoming these biological barriers through precision structural engineering and tunable physicochemical properties. This critical review evaluates the solid-state behavior and architectural design of electrospun transmucosal systems, with a specific focus on the dynamic material-mucosa interface. We dissect the mechanistic basis of nanofiber performance, detailing how polymer chemistry, hydration dynamics, and solid-state drug amorphization collectively govern mucoadhesion, mucus penetration, and release kinetics. Furthermore, we critically analyze advanced architectural strategies, including fast-dissolving matrices, sequential-release multilayers, core-shell configurations, and hierarchical nanoparticle-in-nanofiber assemblies, and highlight how the spatial manipulation of polymeric materials dictates functionality across the oral, nasal, and vaginal mucosa. Finally, we address prevailing translational bottlenecks in materials processing, such as the thermodynamic instability of amorphous solid dispersions during scale-up, while outlining future perspectives in stimuli-responsive smart polymers and device-integrated 3D-printed composite scaffolds. Ultimately, this review establishes that the rational engineering of nanofiber morphology, surface chemistry, and solid-state properties is paramount to advancing next-generation mucosal delivery platforms.
Cyclodextrins (CDs) have emerged as versatile building blocks for regenerative biomaterials owing to their unique host-guest chemistry, biocompatibility, and structural tunability. Beyond their traditional role as pharmaceutical excipients, CDs enable the design of multifunctional platforms capable of controlled therapeutic delivery, biomolecule stabilization, and microenvironment-responsive behavior. This review provides a comprehensive overview of CD-based biomaterials for tissue regeneration, covering their structural features, functionalization strategies, and fabrication into hydrogels, nanoparticles, scaffolds, composite systems, and stimuli-responsive platforms. Particular emphasis is placed on the mechanisms through which CD-based materials regulate therapeutic release, modulate cellular responses, and support tissue repair across bone, cartilage, cardiac, neural, hepatic, skin, and ocular applications. This review further critically discusses safety considerations, regulatory challenges, and translational barriers that currently limit clinical adoption. Emerging opportunities, including personalized regenerative medicine, 3D/4D bioprinting, and AI-assisted biomaterial design, are highlighted as promising directions for the development of next-generation regenerative therapies. Collectively, CD-based biomaterials represent a rapidly evolving platform with significant potential to advance tissue engineering and clinical regeneration.
This research aims to develop and validate a simple, sensitive, and robust reverse-phase high-performance liquid chromatographic (RP-HPLC) method for the estimation of Alpha-Linolenic acid (ALA) isolated from silkworm pupa oil (SPO) using preparative-HPLC (PR-HPLC). Chromatographic separation was performed on a Shimadzu, C-18 column (4.6 × 250 mm, 5 μm particle size) using acetonitrile/water in a ratio of 80:20 with a flow rate of 1 mL/min and detection at a λmax of 242 nm, equipped with a UV detector. The method demonstrated excellent linearity (R2 = 0.9999, p < 0.05) and good accuracy (98.41–102.10
Breast cancer continues to be the most commonly diagnosed cancer among women globally, and despite significant progress in standard treatment approaches, it is still associated with substantial recurrence rates and postoperative complications. Systemic toxicity, drug resistance, poor tumor targeting, and compromised quality of life limit current treatment strategies, such as chemotherapy, radiotherapy, and surgery. In this context, multifunctional electrospun nanofibers have emerged as a promising platform for localized cancer therapy combined with regenerative reconstruction. This review comprehensively summarizes electrospun nanofiber-based systems for breast cancer management and associated biomedical applications. The fabrication techniques, including electrospinning, self-assembly, template synthesis, melt blowing, and centrifugal spinning, are critically discussed along with material selection using natural and synthetic polymers such as chitosan (CS), collagen, gelatin, poly(ε-caprolactone) (PCL), polylactic acid (PLA), and poly(lactic-co-glycolic acid) (PLGA). Special emphasis is placed on advanced nanofiber architectures, including core-shell, pH-responsive, and thermo-responsive systems, which enable controlled and site-specific drug release. Furthermore, the review highlights the role of nanofibers in localized chemotherapy, preventing postoperative recurrence, tissue regeneration, wound healing, cardiovascular repair, gene delivery, and tissue engineering. Recent in vitro and in vivo studies demonstrate that nanofiber-based drug delivery systems significantly enhance therapeutic efficacy while minimizing systemic toxicity. Despite encouraging outcomes, challenges related to large-scale production, mechanical stability, long-term safety, regulatory approval, and clinical translation remain. Future research should focus on scalable fabrication, multifunctional design optimization, and patient-specific therapeutic strategies. Overall, electrospun nanofibers represent a highly versatile and transformative platform for integrated breast cancer therapy and regenerative medicine.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumours, driven by late diagnosis, early metastatic dissemination, and profound resistance to systemic therapies. Increasing evidence indicates that these hallmarks are not solely tumour cell intrinsic but are critically orchestrated by a complex and highly dynamic tumour microenvironment (TME) composed of pancreatic stellate cells (PSCs), cancer-associated fibroblast (CAF) subtypes, immune cells, endothelial and neuronal elements, and a dense extracellular matrix (ECM). This review provides an integrated overview of the cellular and acellular components of the PDAC TME and delineates how their reciprocal crosstalk drives desmoplasia, immune suppression, metabolic reprogramming, epithelial–mesenchymal transition (EMT), pre-metastatic niche formation, and metastatic outgrowth. Particular emphasis is placed on the context-dependent roles of stromal and immune niches in modulating drug delivery, chemoresistance, and failure of immunotherapy, highlighting why indiscriminate stromal depletion has yielded paradoxical outcomes. Building on these mechanistic insights, the review critically examines emerging therapeutic strategies targeting PSCs, CAF subsets, ECM components, myeloid and lymphoid populations, and key signalling pathways, including approaches that normalize stroma, reprogram immunity, or exploit nanocarrier-based delivery systems. Finally, a structured framework is proposed for rational TME-targeted combination regimens that integrate cytotoxic, targeted, and immunotherapeutic agents to overcome current therapeutic barriers in PDAC.
Four-dimensional (4D) printing, the fabrication of stimuli-responsive constructs whose time-dependent behavior is programmed during the printing process itself, has become a crowded research field producing an increasingly repetitive review literature. Most existing reviews catalog materials and applications without addressing the fabrication-criterion boundary between true 4D printing and conventional 3D printing of smart materials, evaluating additive manufacturing platforms by their ability to encode spatiotemporal actuation at the voxel level, or providing organ-specific design guidance that connects printing technique selection to clinical functional requirements. This review addresses these gaps directly. We establish a rigorous fabrication-encoding criterion that distinguishes programmable 4D constructs from post-print-programmed 3D objects, and apply it consistently throughout. We evaluate material extrusion, vat polymerization, powder bed fusion, and volumetric platforms quantitatively against three axes: multi-material interface resolution, voxel-level property control, and process-induced microstructural gradients, providing a design-oriented framework for platform selection. We critically synthesize two underserved application domains, 4D printing in cancer therapeutics and self-forming tubular constructs, and provide tissue-specific fabrication and material recommendations for heart, bone, cartilage, skin, neural, and vascular targets. The integration of AI-augmented closed-loop manufacturing as a quality assurance strategy for clinical translation is also examined. Together, these contributions reframe 4D biomedical printing as an engineering design discipline governed by quantifiable fabrication parameters rather than a catalog of materials demonstrations.
Breast cancer (BC) remains one of the most complex and heterogeneous malignancies, driven by intricate interactions among genetic mutations, hormonal regulation, and environmental influences. The World Health Organization reported approximately 2.3 million BC diagnoses in 2022, accounting for nearly 11.6% of all newly reported cancer cases worldwide. This review highlights recent advances in BC research, emphasizing the integration of molecular profiling with nanomedicine to advance precision oncology. We examine key hereditary risk factors, including mutations in BRCA1, BRCA2, TP53, and PALB2, in the context of genetic predisposition, risk assessment, and preventive interventions. Emerging diagnostic approaches such as liquid biopsies, circulating tumor DNA analysis, and next-generation sequencing are compared with conventional biopsy techniques, emphasizing their potential for minimally invasive, real-time tumor monitoring. Particular attention is given to nano-enabled platforms for enhanced biomarker detection. On the therapeutic front, targeted nanocarrier systems (liposomes, dendrimers, polymeric micelles, exosomes, and antibody–drug conjugates) demonstrate promise in improving drug bioavailability, site-specific delivery, and mitigation of systemic toxicity and multidrug resistance. We outline major translational challenges like tumor heterogeneity, immune evasion, and the complex tumor microenvironment. Looking ahead, the convergence of stimuli-responsive nanoplatforms, RNA-based therapeutics, and biomarker-guided treatment is anticipated to redefine the therapeutic landscape. Overall, this review provides clinicians and researchers with an in-depth understanding of the evolving molecular and nanotechnological strategies driving precision medicine in BC management.
Background Electrospun nanofiber food packaging has advanced rapidly in functional performance. However, a critical knowledge gap persists: the environmental sustainability of these nanomaterials is frequently presumed based on the renewable sourcing of their parent polymers. While numerous existing reviews exhaustively cover use-phase innovations (e.g., barrier and antimicrobial properties), they broadly conflate the theoretical biodegradability of bulk resins with the actual post-consumer fate of electrospun mats, leaving the true environmental impact of the fiber morphology largely uncharacterized. Scope and approach To address this deficit, this review introduces a novel “morphological evidence audit,” distinguishing this manuscript from prior packaging literature. This structural approach systematically decouples assumed sustainability claims by strictly separating end-of-life (EOL) behavior demonstrated directly for true electrospun nanofibers from evidence merely extrapolated from bulk or cast-film analogs. Furthermore, it uniquely evaluates the “antimicrobial paradox,” assessing the distinct ecotoxicological risks of active nanoparticles independently from the degradation of the polymer matrix itself. Key findings and conclusions The audit reveals that while nanoscale morphology accelerates biodegradation in select polyesters, this advantage has not been empirically verified for the majority of biopolymers that dominate the field. Crucially, the literature currently lacks any cradle-to-grave life-cycle assessment for finished electrospun systems. Theoretical sustainability is actively compromised by the degradation-retarding effects of chemical crosslinkers, the ecotoxicity of embedded nanoparticles, and consumer misinterpretation of compostability labels. With stringent regulatory mandates, such as the EU Packaging and Packaging Waste Regulation (PPWR), rapidly approaching, EOL behavior and legal compliance must transition from assumed corollaries of renewable sourcing to primary, first-order design constraints.
This research demonstrates the design and development of a novel dual-targeting, pH-sensitive liposomal (pSL) formulation of 5-Fluorouracil (5-FU), i.e., (5-FU-iRGD-FA-pSL) to manage breast cancer (BC). The motivation to explore this formulation is to overcome the challenges of systemic toxicity and non-specific targeting of 5-FU, a conventional chemotherapeutic agent. The proposed formulation also combines folic acid (FA) and iRGD peptides as targeting ligands to enhance tumor cell specificity and penetration, while the pH-sensitive liposomes ensure the controlled drug release in the acidic tumor microenvironment. The physicochemical characterization revealed that 5-FU-iRGD-FA-pSL possesses optimal size, low polydispersity index, and favorable zeta potential, enhancing its stability and targeting capabilities. In vitro studies demonstrated significantly enhanced cellular uptake, cytotoxicity, and inhibition of cell migration in MCF-7 BC cells compared to free 5-FU and non-targeted liposomal formulations. DAPI staining revealed significant apoptotic features, including chromatin condensation (CC) and nuclear fragmentation (NF), with 5-FU-iRGD-FA-pSL inducing more pronounced apoptosis compared to 5-FU-pSL. Furthermore, in vivo analysis in a BC rat model showed superior anti-tumor efficacy, reduced systemic toxicity, and improved safety profile of the 5-FU-iRGD-FA-pSL formulation. This dual-targeting pSL system presents a promising approach for enhancing the therapeutic index of 5-FU, offering a potential strategy for more effective BC treatment.
The oral bioavailability of drugs is often limited by metabolic barriers, including enzymatic degradation and active efflux processes in the gastrointestinal tract. Piperine, a pungent alkaloid found in black pepper (Piper nigrum), has garnered significant interest as a natural bioenhancer due to its multifaceted ability to inhibit cytochrome P450 enzymes, particularly CYP3A4, and efflux transporters such as P-glycoprotein (P-gp). These actions result in enhanced intestinal absorption and prolonged systemic retention of various therapeutic agents. Additionally, Piperine modulates intestinal permeability and alters the pharmacokinetics of drugs by interfering with first-pass metabolism. Recent developments in nanotechnology have led to innovative formulation strategies, such as nanoemulsions, liposomes, and self-emulsifying drug delivery systems, which further enhance Piperine's solubility, stability, and efficacy. However, despite its promising bioenhancing effects, Piperine exhibits limitations such as poor water solubility, dose-dependent toxicity, reproductive and hepatic concerns, and the potential for significant drug-drug interactions. This review critically examines the mechanistic pathways, formulation advances, pharmacological roles, safety issues, and clinical prospects of Piperine. Furthermore, it emphasizes the need for rigorous clinical trials and regulatory evaluation to validate Piperine's use in pharmaceutical applications. Overall, Piperine represents a potent, yet cautiously applicable, tool in modern drug delivery strategies.
Fucoidans (FU's), sulfated polysaccharides derived predominantly from brown seaweeds, have garnered substantial interest due to their multifunctional biological activities and emerging applications in biomedicine. This review comprehensively examines FU's structural diversity, physicochemical properties, and therapeutic relevance, particularly on native and modified forms. FU content across species ranges from 2 % to 20 % (dry weight), with molecular weights spanning 10-950 kDa and sulfation levels between 5 % and 35 %, all critically influencing bioactivity. Quantitative evaluations reveal that FU's can inhibit tumor cell proliferation with IC50 values ranging from 24 to 72 μg/mL and reduce inflammatory mediators by up to 56 % in in vitro models. Advances in formulation science have enabled the development of FU-based nanoparticles (90-210 nm), hydrogels, microneedles, and scaffolds, achieving up to 87 % encapsulation efficiencies and sustained drug release over 48-72 h. Modified FU's (e.g., oversulfated or conjugated forms) demonstrate enhanced anticoagulant, immunomodulatory, and regenerative effects. This review integrates findings from over two decades (2000-2025), highlighting source-specific properties, bioactivities, and challenges such as low oral bioavailability, structural heterogeneity, and regulatory bottlenecks. Synthesizing structural, pharmacological, and translational insights, this work offers a timely reference that bridges marine-derived biomolecules with next-generation therapeutic platforms.
Carcinoma is a worldwide concern of well-being that leads health concern leading to mor-tality and disability. Although current treatment procedures offer some efficacy, they are not devoid of constraints and potential adverse reactions. Over the past few years, tremendous progress has emerged in newer strategies like immunotherapy and novel drug delivery systems, such as designing formula-tions utilising utilizing non-lamellar liquid-crystalline nanoparticles, known as lyotropic systems. Among them, cubosomes are one of the distinct categories of nanocarriers, formed by utilising utilizing precise proportions of amphiphilic lipids. Cubosomes are known for their ability to be compatible with living organisms and their flexibility in transporting drugs, allowing for the administration of pharma-ceuticals through many pathways. Several preclinical investigations have been reported to explore the future of cubosomes in cancer therapy and theranostic applications. The findings suggest that nano-technology and cancer therapies like immunotherapy have significant potential for tailored and effi-cient treatment approaches. Cubosomes can offer a promising contribution to the discipline of cancer research and the goal of enhancing therapeutic innovations. However, extensive research is required to confirm the safety, drug release mechanism, and stability of these nanocarriers. It covers a brief overview of cancer therapy including immunotherapy, advantages of targeted drug delivery, general aspects on of cubosomes, types of cubosomes, structural components, and preparation methods, fol-lowed by the mechanism of release, and discoveries on cubosomes as drug delivery for various cancers covering breast, colorectal, lung, liver, cervical, skin, etc. along with the future perspectives of other novel therapies like immunology in cancer.
Oral cancer, currently ranked 16th among the most prevalent malignancies worldwide according to GLOBOCAN, presents significant challenges to global oral health. Conventional treatment modalities such as surgery, radiation, and chemotherapy often have limitations, prompting the need for innovative therapeutic approaches. Tissue engineering has emerged as a promising solution aimed at developing biocompatible, functional, and biologically responsive tissue constructs. This approach involves the integration of cells, bioactive compounds, and scaffolds to enhance treatment efficacy. Electrospun nanofibers, mimicking the extracellular matrix, exhibit considerable potential in addressing complex oral health issues by influencing cellular behavior. The versatility of electrospinning technology allows for the fabrication of fiber scaffolds with high surface area, making them ideal for localized delivery of bioactive compounds or pharmaceuticals. Enhancing these electrospun scaffolds with growth factors, nanoparticles, and biologically active substances significantly increases their therapeutic appeal in oral cancer management. This review offers a comprehensive examination of the various applications of electrospun nanofibers in oral cancer therapy. Utilizing electronic databases such as PubMed, CrossREF, and Google Scholar, we conducted an extensive review of relevant literature concerning "electrospun nanofibers" and their therapeutic potential in oral cancer treatment. Key topics addressed include engineering methodologies, drug diffusion mechanisms, factors influencing nanofiber scaffold design, toxicity concerns, and clinical implications. The findings underscore the transformative potential of electrospun nanofibers in revolutionizing oral cancer therapy.