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Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co3+ and Co2+ caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2 through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2 nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

Abstract Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e−/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.

Fungal infections, though affecting healthcare globally, receive insufficient attention in clinical and academic settings. Invasive fungal infections, particularly caused by combat wounds, have been identified as a critical threat by the US Department of Defense. Monotherapy with traditional antifungals is often insufficient, and so combination therapies are explored to enhance treatment efficacy. However, systemic combination treatments can result in severe adverse effects, suggesting the need for localised delivery systems, such as drug-loaded electrospun patches, to administer antifungals directly to the infection site. This proof-of-concept study hypothesised that dual amorolfine and terbinafine therapy slowly releasing from electrospun patches would be an effective way of eradicating Candida albicans when the patch was applied directly to the fungal colony. The feasibility of creating electrospun materials loaded with amorolfine and terbinafine for combination antifungal therapy was investigated. Electrospinning was used to fabricate polycaprolactone (PCL) patches with varying drug loadings (2.5%, 5%, and 10% w/w) of amorolfine and terbinafine either individually or in combination. The incorporation of both drugs in the fibres was confirmed, with the drugs predominantly in an amorphous state. Results showed that combination therapy patches had a significantly greater and prolonged antifungal effect compared to monotherapy patches, with larger zones of inhibition and sustained efficacy over at least 7 days. This study therefore demonstrates that PCL-based electrospun patches containing amorolfine and terbinafine provide superior antifungal activity against C. albicans compared to monotherapy patches. This approach could lower required drug doses, reducing adverse effects, and enhance patient compliance due to prolonged drug release, leading to more effective antifungal therapy.

Polysorbate 80 is one of the most commonly used surfactants in the formulation of biotherapeutics, particularly those administered intravenously. It comprises a mixture of fatty acids but is not a precisely defined chemical entity. Hence, there are a range of different grades available in the market, all meeting compendial specifications. Polysorbate 80 is known to undergo auto degradation producing protein-damaging by-products, and to contain residual impurities that can have an impact on the stability and integrity of the active ingredients in the formulation. Given the variety of chemical compositions that polysorbate 80 can comprise, the degradation pathway and extent could vary depending on the grade used in the formulation. This study compared the physical and chemical properties of four commercially available polysorbate 80 grades with different degrees of purity and oleic acid content and investigated their degradation profiles. This study did not find any significant differences between the properties or degradation profiles of the four grades investigated. Further studies are underway to understand the formation of other reactive impurities and their impact on the model protein formulations.

The combination of poorly-soluble drugs with small molecule co-formers to generate amorphous solid dispersions (ASDs) has great potential to improve dissolution rate and kinetic solubility, and thus increase the bioavailability of these active ingredients. However, such ASDs are known to be unstable and to crystallise upon storage or heating. In this work, we explore the crystallisation of flufenamic acid (FFA) from ASDs prepared with trehalose. FFA-trehalose mixtures were prepared at a range of w/w composition ratios, heated to melting and crash cooled to form ASDs. They were then subject to a further heat/cool cycle, which was monitored by simultaneous differential scanning calorimetry – X-ray diffraction to observe the phase changes occurring. These varied with the composition of the blend. Upon short-term storage, formulations with low trehalose contents (FFA:trehalose 5:1 w/w) recrystallised into form I FFA, while higher trehalose contents crystallised to FFA form IV. When heated, all FFA trehalose combinations ultimately recrystallised into form I before melting. Upon a second cooling cycle, systems with low trehalose content (FFA:trehalose 5:1 w/w) recrystallised into form IV, while higher trehalose contents led to FFA form I. It is thus clear that even with a single excipient it is possible to control the crystallisation pathway through judicious choice of the formulation parameters.

Oxidative stress plays a critical role in the development of chronic ocular conditions including cataracts, age-related macular degeneration, and diabetic retinopathy. There is a need to explore the potential of topical antioxidants to slow the progression of those conditions by mediating oxidative stress and maintaining ocular health. Selenium has attracted considerable attention because it is a component of selenoproteins and antioxidant enzymes. The application of selenium to a patient can increase selenoprotein expression, counteracting the effect of reactive oxygen species by increasing the presence of antioxidant enzymes, and thus slowing the progression of chronic ocular disorders. Oxidative stress effects at the biomolecular level for prevalent ocular conditions are described in this review along with some of the known defensive mechanisms, with a focus on selenoproteins. The importance of selenium in the eye is described, along with a discussion of selenium studies and uses. Selenium’s antioxidant and anti-inflammatory qualities may prevent or delay eye diseases. Recent breakthroughs in drug delivery methods and nanotechnology for selenium-based ocular medication delivery are enumerated. Different types of selenium may be employed in formulations aimed at managing ocular oxidative stress conditions.

The overexpression of heat shock proteins (HSPs) in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments, inducing thermoresistance and thus diminishing the treatment efficacy. Here, we report a distinct “non-inhibitor involvement” strategy to address this issue through engineering a calcium-based nanocatalyst (G/A@CaCO3-PEG). The constructed nanocatalyst consists of calcium carbonate (CaCO3)-supported glucose oxidase (GOD) and 2D antimonene quantum dots (AQDs), with further surface modification by lipid bilayers and polyethylene glycol (PEG). The engineered G/A@CaCO3-PEG nanocatalyst features prolonged blood circulation, which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment, resulting in rapid release of drug cargo in the tumor microenvironment. The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate (ATP) and subsequent down-regulation of HSP expression. This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells’ thermoresistance. Consequently, synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy. Systematic in vitro and in vivo evaluations have demonstrated that G/A@CaCO3-PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate (83.92%). This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply.

Electrospun nanofibrous membranes have garnered significant attention in antimicrobial applications, owing to their intricate three-dimensional network that confers an interconnected porous structure, high specific surface area, and tunable physicochemical properties, as well as their notable capacity for loading and sustained release of antimicrobial agents. Tailoring polymer or hybrid-based nanofibrous membranes with stimuli-responsive characteristics further enhances their versatility, enabling them to exhibit broad-spectrum or specific activity against diverse microorganisms. In this review, we elucidate the pivotal advancements achieved in the realm of stimuli-responsive antimicrobial electrospun nanofibers operating by light, temperature, pH, humidity, and electric field, among others. We provide a concise introduction to the strategies employed to design smart electrospun nanofibers with antimicrobial properties. The core section of our review spotlights recent progress in electrospun nanofiber-based systems triggered by single- and multi-stimuli. Within each stimulus category, we explore recent examples of nanofibers based on different polymers and antimicrobial agents. Finally, we delve into the constraints and future directions of stimuli-responsive nanofibrous materials, paving the way for their wider application spectrum and catalyzing progress toward industrial utilization.

In exploring the difference in the wettability of fibers with various structures, three inner constructions of fibers, namely, uniaxial, Janus and chimeric Janus, have been fabricated by electrospinning. In electrospun fibers, polyvinyl pyrrolidone and cellulose acetate were used as a polymer matrix and ketoprofen was used as a model drug. Morphologies and inner structures were respectively investigated by scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). Physical states and compatibilities of materials were detected by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Water contact angle (WCA) tests were conducted to determine the difference between wettability and wetting time among assorted fiber membranes. Results showed that the wettability gradient could drive water movement and wetting, which resulted in the rapid decrease of the WCA, to prepare Janus and chimeric Janus fiber membranes compared with uniaxial fiber membranes. Otherwise, in vitro drug release experiments were carried out and four fitting models were applied in matching release profiles. The results showed that electrospun fiber membranes belonged to sustained-release systems and such membranes were influenced by drug diffusion and backbone corrosion effects. In this study, whether electrospun multilayer Janus fibers could affect wettability and drug release was investigated.

Since its discovery, small interfering RNA (siRNA) has revolutionised the field of gene silencing therapy because of its great potential in targeting diseases that were considered untreatable. Although several siRNA drugs are already in the market, many challenges remain to be addressed before siRNA therapies can realise their full potential including extra-hepatic delivery and improved endosomal escape. Dendritic polypeptides are attractive carriers for siRNA because of their wide range of defined structures that can be made. In this work, we report the on-going development of histidylated poly(lysine) dendrimers (G3KH) as carriers for siRNA. Histidine-capped lysine dendrimers were synthesised via HBTU/HOBt coupling reaction in solution. 1H NMR data confirms the structure of G3KH dendrimers; however, although traces of impurities were also observed. Histidylated lysine dendrimers could efficiently condense short double-strand DNA oligos (used as a model for siRNA) to form cationic nanoparticles of less than 100 nm in size

The restoration of cartilage damage is a slow and not always successful process. Kartogenin (KGN) has significant potential in this space—it is able to induce the chondrogenic differentiation of stem cells and protect articular chondrocytes. In this work, a series of poly(lactic-co-glycolic acid) (PLGA)-based particles loaded with KGN were successfully electrosprayed. In this family of materials, PLGA was blended with a hydrophilic polymer (either polyethyleneglycol (PEG) or polyvinylpyrrolidone (PVP)) to control the release rate. Spherical particles with sizes in the range of 2.4–4.1 µm were fabricated. They were found to comprise amorphous solid dispersions, with high entrapment efficiencies of >93%. The various blends of polymers had a range of release profiles. The PLGA-KGN particles displayed the slowest release rate, and blending with PVP or PEG led to faster release profiles, with most systems giving a high burst release in the first 24 h. The range of release profiles observed offers the potential to provide a precisely tailored profile via preparing physical mixtures of the materials. The formulations are highly cytocompatible with primary human osteoblasts.

Abstract Recent advances in bioimaging, biochemistry, and bioinformatics have facilitated the development of personalized and precision medicine. Theranostics, combining imaging modalities and therapeutic agents, have garnered a lot of attention in this context, owing to their potential to monitor and control treatment for individual patients. A promising strategy to achieve this goal involves the development of therapy guided by magnetic resonance imaging (MRI). MRI has a high degree of soft tissue contrast, low invasiveness, high depth of penetration and good spatial resolution. MRI‐guided therapy could thus allow precise and time‐resolved assessment of disease conditions and therapeutic progression. This article will give a brief introduction to the principles of MRI, and describe recently developed strategies to produce MRI‐guided therapies. A number of theranostics based on T1, T2, or chemical exchange saturation transfer (CEST) MRI have been explored to track the route of drug carriers in vivo and image diseased tissue so as to enhance bioavailability, overcome complex delivery barriers, and assess therapeutic responses. In addition, the integration of thermal therapy and MRI imaging offers a strategy to noninvasively identify target areas, plan treatment, and provide real‐time assessment of the efficacy of tumor ablation. We also discuss advances in intelligent nanoparticles combining small molecule drugs, thermal treatment and multimodal imaging, arguing that these multifunctional agents can further improve therapeutic outcomes.

A series of new core-shell fibers were developed containing anticancer drugs (5-fluorouracil or ferulic acid) and their cyclodextrin inclusion complexes, with a gadolinium-based magnetic resonance imaging (MRI) contrast agent. These were prepared by electrospinning, a simple method for producing ultra-fine fibers through the application of a strong electrostatic force on a polymer solution. The shell of the fibers was formed from Eudragit S100, and the drugs were loaded in the core. Scanning electron microscopy images showed the formation of smooth ribbon-like fibers, with diameters ranging from 1.4 to 5.1 μm, and transmission electron microscopy reveals a transparent interface between the core and shell compartments. X-ray diffraction and differential scanning calorimetry data confirmed the encapsulation of the drug into the cyclodextrin cavity and the formation of amorphous solid dispersions in the fibers. Drug release from the systems at pH 1 and 7 showed that all the drug loading was released within one hour at pH 1. Based on these results, it is proposed that the relatively low molecular weight drugs were able to diffuse out of the system into the release medium at acidic pH, despite the insolubility of the shell polymer under these conditions. These findings have important implications for the design of electrospun drug delivery systems.

Abstract Background It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal. Results In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size

Abstract Background Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends “don’t eat me” signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells. Results In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~ 192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations. Conclusions Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.

Therapeutic proteins and peptides are clinically important, offering potency while reducing the potential for off-target effects. Research interest in developing therapeutic polypeptides has grown significantly during the last four decades. However, despite the growing research effort, maintaining the stability of polypeptides throughout their life cycle remains a challenge. Electrohydrodynamic (EHD) techniques have been widely explored for encapsulation and delivery of many biopharmaceuticals. In this work, we explored monoaxial electrospraying for encapsulation of bovine liver catalase, investigating the effects of the different components of the electrospraying solution on the integrity and bioactivity of the enzyme. The catalase was successfully encapsulated within polymeric particles made of polyvinylpyrrolidone (PVP), dextran, and polysucrose. The polysorbate 20 content within the electrospraying solution (50 mM citrate buffer, pH 5.4) affected the catalase loading—increasing the polysorbate 20 concentration to 500 μg/mL resulted in full protein encapsulation but did not prevent loss in activity. The addition of ethanol (20% v/v) to a fully aqueous solution improves the electrospraying process by reducing surface tension, without loss of catalase activity. The polymer type was shown to have the greatest impact on preserving catalase activity within the electrosprayed particles. When PVP was the carrier there was no loss in activity compared with fresh aqueous solutions of catalase. The optimum particles were obtained from a 20% w/v PVP or 30% w/v PVP-trehalose (1:1 w/w) solution. The addition of trehalose confers stability advantages to the catalase particles. When trehalose-PVP particles were stored at 5 °C, enzymatic activity was maintained over 3 months, whereas for the PVP-only analogue a 50% reduction in activity was seen. This demonstrates that processing catalase by monoaxial electrospraying can, under optimised conditions, result in stable polymeric particles with no loss of activity.

Aggregation resulting from the self-association of peptide molecules remains a major challenge during preformulation. Whereas certain organic solvents are known to promote aggregation, ethanol (EtOH) is capable of disrupting interactions between peptide molecules. It is unclear whether it is beneficial or counterproductive to include EtOH in formulations of short peptides. Here, we employed molecular dynamics simulations using the DAFT protocol and MARTINI force field to predict the formation of self-associated dimers and to estimate the stability of a GLP-1-like peptide (G48) in 0–80% aqueous EtOH solutions. Both simulation and experimental data reveal that EtOH leads to a remarkable increase in the conformational stability of the peptide when stored over 15 days at 27 °C. In the absence of EtOH, dimerisation and subsequent loss in conformational stability (α-helix → random coil) were observed. EtOH improved conformational stability by reducing peptide–peptide interactions. The data suggest that a more nuanced approach may be applied in formulation decision making and, if the native state of the peptide is an α-helix organic solvent, such as EtOH, may enhance stability and improve prospects of long-term storage.

Side-by-side electrospinning is a powerful but challenging technology that can be used to prepare Janus nanofibers for various applications. In this work, cellulose acetate (CA) and polycaprolactone (PCL) were used as polymer carriers for silver nanoparticles (Ag NPs) and lavender oil (LO), respectively, processing these into two-compartment Janus fibers. A bespoke spinneret was used to facilitate the process and prevent the separation of the working fluids. The process of side-by-side electrospinning was recorded with a digital camera, and the morphology and internal structure of the products were characterized by electron microscopy. Clear two-compartment fibers are seen. X-ray diffraction patterns demonstrate silver nanoparticles have been successfully loaded on the CA side, and infrared spectroscopy indicates LO is dispersed on the PCL side. Wetting ability and antibacterial properties of the fibers suggested that PCL-LO//CA-Ag NPs formulation had strong antibacterial activity, performing better than fibers containing only one active component. The PCL-LO//CA-Ag NPs had a 20.08 ± 0.63 mm inhibition zone for E. coli and 19.75 ± 0.96 mm for S. aureus. All the fibers had water contact angels all around 120°, and hence, have suitable hydrophobicity to prevent water ingress into a wound site. Overall, the materials prepared in this work have considerable promise for wound healing applications.

In this study, a pH-responsive controlled-release mesoporous silica nanoparticle (MSN) formulation was developed. The MSNs were functionalized with a histidine (His)-tagged targeting peptide (B3int) through an amide bond, and loaded with an anticancer drug (cisplatin (CP)) and a lysosomal destabilization mediator (chloroquine (CQ)). Cu2+ was then used to seal the pores of the MSNs via chelation with the His-tag. The resultant nanoparticles showed pH-responsive drug release, and could effectively target tumor cells via the targeting effect of B3int. The presence of CP and Cu2+ permits reactive oxygen species to be generated inside cells; thus, the chemotherapeutic effect of CP is augmented by chemodynamic therapy. In vitro and in vivo experiments showed that the nanoparticles are able to effectively kill tumor cells. An in vivo cancer model revealed that the nanoparticles increase apoptosis in tumor cells, and thereby diminish the tumor volume. No off-target toxicity was noted. It thus appears that the functionalized MSNs developed in this work have great potential for targeted, synergistic anticancer therapies.

Electrospinning is an inexpensive and powerful method that employs a polymer solution and strong electric field to produce nanofibers. These can be applied in diverse biological and medical applications. Due to their large surface area, controllable surface functionalization and properties, and typically high biocompatibility electrospun nanofibers are recognized as promising materials for the manufacturing of drug delivery systems. Electrospinning offers the potential to formulate poorly soluble drugs as amorphous solid dispersions to improve solubility, bioavailability and targeting of drug release. It is also a successful strategy for the encapsulation of nutraceuticals. This review aims to briefly discuss the concept of electrospinning and recent progress in manufacturing electrospun drug delivery systems. It will further consider in detail the encapsulation of nutraceuticals, particularly probiotics.

The socioeconomic impact of osteochondral (OC) damage has been increasing steadily over time in the global population, and the promise of tissue engineering in generating biomimetic tissues replicating the physiological OC environment and architecture has been falling short of its projected potential. The most recent advances in OC tissue engineering are summarised in this work, with a focus on electrospun and 3D printed biomaterials combined with stem cells and biochemical stimuli, to identify what is causing this pitfall between the bench and the patients’ bedside. Even though significant progress has been achieved in electrospinning, 3D-(bio)printing, and induced pluripotent stem cell (iPSC) technologies, it is still challenging to artificially emulate the OC interface and achieve complete regeneration of bone and cartilage tissues. Their intricate architecture and the need for tight spatiotemporal control of cellular and biochemical cues hinder the attainment of long-term functional integration of tissue-engineered constructs. Moreover, this complexity and the high variability in experimental conditions used in different studies undermine the scalability and reproducibility of prospective regenerative medicine solutions. It is clear that further development of standardised, integrative, and economically viable methods regarding scaffold production, cell selection, and additional biochemical and biomechanical stimulation is likely to be the key to accelerate the clinical translation and fill the gap in OC treatment.

Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N–vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.

Abstract Theranostic formulations, integrating both diagnostic and therapeutic functions into a single platform, hold great potential for precision medicines. In this work, a biodegradable theranostic based on hollow mesoporous organosilica nanoparticles (HMONs) is reported and explored for ultrasound/photoacoustic dual‐modality imaging guided chemo‐photothermal therapy of cancer. The HMONs prepared are endowed with glutathione‐responsive biodegradation behavior by incorporating disulfide bonds into their framework. The nanoparticles are loaded with indocyanine green (ICG) and perfluoropentane (PFP). The former acts as a photothermal agent and the latter can generate bubbles for ultrasound imaging. A paclitaxel prodrug is developed to both serve as a redox‐sensitive gatekeeper controlling ICG release from the HMON pores and a chemotherapeutic. ICG generates mild hyperthermia upon exposure to an 808 nm laser, and this in turn leads to a liquid–gas phase transition of PFP, resulting in the generation of bubbles which can be used for ultrasound imaging. The platform is found to have excellent properties for both ultrasound and photoacoustic imaging. In addition, both in vitro and in vivo results show that the nanoparticles provide potent synergistic chemo‐photothermal therapy. The material developed in this work thus has great potential for exploitation in advanced cancer therapies.

Although electrospun nanofibers are expanding their potential commercial applications in various fields, the issue of energy savings, which are important for cost reduction and technological feasibility, has received little attention to date. In this study, a concentric spinneret with a solid Teflon-core rod was developed to implement an energy-saving electrospinning process. Ketoprofen and polyvinylpyrrolidone (PVP) were used as a model of a poorly water-soluble drug and a filament-forming matrix, respectively, to obtain nanofibrous films via traditional tube-based electrospinning and the proposed solid rod-based electrospinning method. The functional performances of the films were compared through in vitro drug dissolution experiments and ex vivo sublingual drug permeation tests. Results demonstrated that both types of nanofibrous films do not significantly differ in terms of medical applications. However, the new process required only 53.9% of the energy consumed by the traditional method. This achievement was realized by the introduction of several engineering improvements based on applied surface modifications, such as a less energy dispersive air-epoxy resin surface of the spinneret, a free liquid guiding without backward capillary force of the Teflon-core rod, and a smaller fluid–Teflon adhesive force. Other non-conductive materials could be explored to develop new spinnerets offering good engineering control and energy savings to obtain low-cost electrospun polymeric nanofibers.

Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological barriers, suboptimal biodistribution, and some proclivity for immunogenicity. Frequent administration of polypeptides is generally required to maintain adequate therapeutic levels, which can limit efficacy and compliance while increasing adverse reactions. Many strategies to increase the duration of action of therapeutic polypeptides have been described with many clinical products having been developed. This review describes approaches to optimise polypeptide delivery organised by the commonly used routes of administration. Future innovations in formulation may hold the key to the continued successful development of proteins and peptides with optimal clinical properties.

Electrospinning has emerged as a powerful strategy to develop controlled release drug delivery systems but the effects of post-fabrication solvent vapor annealing on drug-loaded electrospun fibers have not been explored to date. In this work, electrospun poly(ε-caprolactone) (PCL) fibers loaded with the hydrophobic small-molecule spironolactone (SPL) were explored. Immediately after fabrication, the fibers are smooth and cylindrical. However, during storage the PCL crystallinity in the fibers is observed to increase, demonstrating a lack of stability. When freshly-prepared fibers are annealed with acetone vapor, the amorphous PCL chains recrystallize, resulting in the fiber surfaces becoming wrinkled and yielding shish-kebab like structures. This effect does not arise after the fibers have been aged. SPL is found to be amorphously dispersed in the PCL matrix both immediately after electrospinning and after annealing. In vitro dissolution studies revealed that while the fresh fibers show a rapid burst of SPL release, after annealing more extended release profiles are observed. Both the rate and extent of release can be varied through changing the annealing time. Further, the annealed formulations are shown to be stable upon storage.

In this study, curcumin-loaded porous poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were prepared and surface modified with red blood cell membranes (RBCM) to yield biomimetic RBCM-p-PLGA@Cur NPs. The NPs displayed a visible cell-membrane structure at their exterior and had a uniform size of 162 ± 3 nm. In vitro studies showed that drug release from non-porous PLGA NPs was slow and that much of the drug remained trapped in the NPs. In contrast, release was accelerated from the porous PLGA NPs, and after the RBCM coating, a sustained release over 48 h was obtained. Confocal microscopy and flow cytometry results revealed that the RBCM-p-PLGA NPs led to a greater cellular uptake by H22 hepatocarcinoma cells than the uncoated analogue NPs, but could avoid phagocytosis by macrophages. The drug-free formulations were highly biocompatible, while the drug-loaded systems were effective in killing cancer cells. RBCM-p-PLGA@Cur NPs possess potent anti-tumor activity in a murine H22 xenograft cancer model (in terms of reduced tumor volume and mass, as well as inducing apoptosis of tumor cells), and have no observable systemic toxicity. Overall, our study demonstrates that the use of the RBCM to cloak nanoscale drug delivery systems holds great promise for targeted cancer treatment, and can ameliorate the severe side effects currently associated with chemotherapy.

The formation of nanoscale fibers from pH-sensitive polymers is a route which has been widely explored for targeted drug delivery. In particular, the Eudragit L100 and S100 families of polymers have received significant attention for this purpose. However, while in some cases it is shown that making drug-loaded Eudragit polymers effectively prevents drug release in low-pH media where the polymer is insoluble, this is not always the case, and other studies have reported significant amounts of drug release at acidic pHs. In this study, we sought to gain insight into the factors influencing the release of active ingredients from Eudragit S100 (ES100) fibers. A family of materials was prepared loaded with the model active ingredients (AIs) benzoic acid, 1-naphthoic acid, 1-naphthylamine, and 9-anthracene carboxylic acid. Analogous systems were prepared with an AI-loaded core and an ES100 sheath. The resultant fibers were smooth and cylindrical in the majority of cases, and X-ray diffraction and differential scanning calorimetry showed them to comprise amorphous solid dispersions. When AI release from the monolithic fibers was probed, it was found that there was significant release at pH 1 in all cases except with 9-anthracene carboxylic acid. Analysis of the results indicated that both the molecular weight of the AI and its acidity/basicity are important in controlling release, with lower molecular weight AIs and basic species released more quickly. The same release trends are seen with the core/shell fibers, but AI release at pH 1 is attenuated. The most significant change between the monolithic and core/shell systems was observed in the case of 1-naphthylamine. Mathematical equations were devised to connect molecular properties and AI release under acidic conditions.