Influence of Pore Size and Surface Functionalization of Mesoporous Silica Nanoparticles on the Solubility and Antioxidant Activity of Confined Coenzyme Q10.

Coenzyme Q10 is a potent antioxidant that plays an important role in the maintenance of various biochemical pathways of the body and has a wide range of therapeutic applications. However, it has low aqueous solubility and oral bioavailability. Mesoporous silica nanoparticles (MCM-41 and SBA-15 types) exhibiting varying pore sizes and modified with phosphonate and amino groups were used to study the influence of pore structure and surface chemistry on the solubility, in vitro release profile, and intracellular ROS inhibition activity of coenzyme Q10. The particles were thoroughly characterized to confirm the morphology, size, pore profile, functionalization, and drug loading. Surface modification with phosphonate functional groups was found to have the strongest impact on the solubility enhancement of coenzyme Q10 when compared to that of pristine and amino-modified particles. Phosphonate-modified MCM-41 nanoparticles (i.e., MCM-41-PO3) induced significantly higher coenzyme Q10 solubility than the other particles studied. Furthermore, MCM-41-PO3 led to a twofold decrease in ROS generation in human chondrocyte cells (C28/I2), compared to the free drug in a DMSO/DMEM mixture. The results confirmed the significant contribution of small pore size and negative surface charge of MSNs that enable coenzyme Q10 confinement to allow enhanced drug solubility and antioxidant activity.

Sortase A Inhibitor Protein Nanoparticle Formulations Demonstrate Antibacterial Synergy When Combined with Antimicrobial Peptides.

Sortase A (SrtA) is an enzyme which attaches proteins, including virulence factors, to bacterial cell walls. It is a potential target for developing anti-virulence agents against pathogenic and antimicrobial resistant bacteria. This study aimed to engineer 𝛽-lactoglobulin protein nanoparticles (PNPs) for encapsulating safe and inexpensive natural SrtA inhibitors (SrtAIs; trans-chalcone (TC), curcumin (CUR), quercetin (QC), and berberine (BR)) to improve their poor aqueous dispersibility, to screen for synergy with antimicrobial peptides (AMPs), and to reduce the cost, dose, and toxicity of AMPs. Minimum inhibitory concentration (MIC), checkerboard synergy, and cell viability assays were performed for SrtAI PNPs against Gram-positive (methicillin-sensitive and -resistant S. aureus) and Gram-negative (E. coli, P. aeruginosa) bacteria alone and combined with leading AMPs (pexiganan, indolicidin, and a mastoparan derivative). Each SrtAI PNP inhibited Gram-positive (MIC: 62.5-125 µg/mL) and Gram-negative (MIC: 31.3-500 µg/mL) bacterial growth. TC PNPs with pexiganan demonstrated synergy against each bacteria, while BR PNPs with pexiganan or indolicidin provided synergy towards S. aureus. Each SrtAI PNP inhibited SrtA (IC50: 25.0-81.8 µg/mL), and did not affect HEK-293 cell viability at their MIC or optimal synergistic concentrations with AMPs. Overall, this study provides a safe nanoplatform for enhancing antimicrobial synergy to develop treatments for superbug infections.

Extracellular Vesicle Nanoarchitectonics for Novel Drug Delivery Applications.

Extracellular vesicles (EVs) can transfer intercellular messages in various (patho)physiological processes and transport biomolecules to recipient cells. EVs possess the capacity to evade the immune system and remain stable over long periods, identifying them as natural carriers for drugs and biologics. However, the challenges associated with EVs isolation, heterogeneity, coexistence with homologous biomolecules, and lack of site-specific delivery, have impeded their potential. In recent years, the amalgamation of EVs with rationally engineered nanostructures has been proposed for achieving effective drug loading and site-specific delivery. With the advancement of nanotechnology and nanoarchitectonics, different nanostructures with tunable size, shapes, and surface properties can be integrated with EVs for drug loading, target binding, efficient delivery, and therapeutics. Such integration may enable improved cellular targeting and the protection of encapsulated drugs for enhanced and specific delivery to target cells. This review summarizes the recent development of nanostructure amalgamated EVs for drug delivery, therapeutics, and real-time monitoring of disease progression. With a specific focus on the exosomal cargo, diverse drug delivery system, and biomimetic nanostructures based on EVs for selective drug delivery, this review also chronicles the needs and challenges of EV-based biomimetic nanostructures and provides a future outlook on the strategies posed.

Oral Delivery of ß-Lactoglobulin-Nanosphere-Encapsulated Resveratrol Alleviates Inflammation in Winnie Mice with Spontaneous Ulcerative Colitis.

Resveratrol (RES) is a nutraceutical with promising anti-inflammatory properties for the treatment of inflammatory bowel diseases (IBD). However, the clinical effectiveness of resveratrol as an oral anti-inflammatory agent is hindered by its extremely poor solubility and poor stability. In this study, we encapsulated resveratrol in ß-lactoglobulin (BLG) nanospheres and systematically analyzed their formulation parameters in vitro followed by a thorough in vivo anti-inflammatory testing in a highly specialized spontaneous murine UC model (Winnie mice model). Complexation of resveratrol with BLG increased the aqueous solubility of resveratrol by ≈1.7 times with 10% w/w loading. Additionally, the in vitro dissolution of resveratrol from the particles was found to be higher compared to resveratrol alone, resulting in >90% resveratrol dissolution in ∼8 h. The anti-inflammatory activity of resveratrol was examined for the first time in Winnie mice, a mouse model that closely represents the clinical signs of IBD. At a 50 mg/kg oral dose for 2 weeks, BLG-RES significantly improved both % body weight and disease activity index (DAI), compared to free resveratrol in Winnie mice. Importantly, histological evaluations revealed a similar trend with striking improvement in the pathology of the colon via an increase in goblet cell numbers and recovery of colonic epithelium. BLG-RES significantly increased the expression level of cytokine interleukin-10 (Il10), which confirms the reduction in inflammation potentially because of the increased dissolution and stability of resveratrol by complexation with BLG. This comprehensive study demonstrates the effectiveness of biocompatible nanomaterials such as BLG in oral delivery of poorly soluble anti-inflammatory molecules such as resveratrol in the treatment of IBD.

Emerging Nanomedicines for the Treatment of Atopic Dermatitis.

Globally, the prevalence of Atopic dermatitis (AD) is significantly increasing and affecting around 20% of population including children. Complex interactions amongst abnormality in epidermal barrier function, environment, infectious agents and immunological defects are considered as key factors in the pathogenesis of AD. Although the role of oxidative stress has been studied in some skin diseases, investigation of the same in AD is intermittent. Calcineurin inhibitors and/or topical corticosteroids are currently available; however, it causes atrophy of the skin, burning sensation, and systemic side effects which leads to poor patient compliance. These limitations provoke the strong need to develop an innovative approach in managing AD. Nanomaterials for effective drug delivery to skin conditions such as AD have attracted a lot of attention owing to its ability to encapsulate, protect, and release the cargo at the diseased skin site. However, there are lots of unmet challenges especially in terms of development of non-toxic formulations and clinical translation of established nanomedicines in the form of accessible products. Numerous formulations have emerged as carrier for poorly soluble and permeable drugs, viz., lipidic, polymeric, metal, silica, liposomes, hydrocarbon gels and this field is evolving. This review is intended to provide an insight incidences associated with pathophysiology of AD and challenges with existing treatments of AD. Focus is kept on reviewing current development and emerging nanomedicines for effective treatment of AD. The review also inculcates merits of several nanomedicines in overcoming challenges of existing products and its future implications.

Environmental Copper Sensor Based on Polyethylenimine-Functionalized Nanoporous Anodic Alumina Interferometers.

Anthropogenic copper pollution of environmental waters from sources such as acid mine drainage, antifouling paints, and industrial waste discharge is a major threat to our environment and human health. This study presents an optical sensing system that combines self-assembled glutaraldehyde-cross-linked double-layered polyethylenimine (PEI-GA-PEI)-modified nanoporous anodic alumina (NAA) interferometers with reflectometric interference spectroscopy (RIfS) for label-free, selective monitoring of ionic copper in environmental waters. Calibration of the sensing system with analytical solutions of copper shows a linear working range between 1 and 100 mg L-1, and a low limit of detection of 0.007 ± 0.001 mg L-1 (i.e., ∼0.007 ppm). Changes in the effective optical thickness (ΔOTeff) of PEI-GA-PEI-functionalized NAA interferometers are monitored in real-time by RIfS, and correlated with the amount of ionic copper present in aqueous solutions. The system performance is validated through X-ray photoelectron spectroscopy (XPS) and the spatial distribution of copper within the nanoporous films is characterized by time-of-flight-secondary ion mass spectroscopy (TOF-SIMS). The specificity and chemical selectivity of the PEI-GA-PEI-NAA sensor to Cu2+ ions is verified by screening six different metal ion solutions containing potentially interfering ions such as Al3+, Cd2+, Fe3+, Pb2+, Ni2+, and Zn2+. Finally, the performance of the PEI-GA-PEI-NAA sensor for real-life applications is demonstrated using legacy acid mine drainage liquid and tap water for qualitative and quantitative detection of copper ions. This study provides new opportunities to develop portable, cost-competitive, and ultrasensitive sensing systems for real-life environmental applications.

In Vitro Dissolution, Cellular Membrane Permeability, and Anti-Inflammatory Response of Resveratrol-Encapsulated Mesoporous Silica Nanoparticles.

Sizing drugs down to the submicron and nanometer scale using nanoparticles has been extensively used in pharmaceutical industries to overcome the poor aqueous solubility of potential therapeutic agents. Here, we report the encapsulation and release of resveratrol, a promising anti-inflammatory and anticancer nutraceutical, from the mesopores of MCM-48-type silica nanospheres of various particle sizes, i.e., 90, 150, and 300 nm. Furthermore, the influence of the carrier pore size on drug solubility was also evaluated (3.5 vs 7 nm). From our results, it is observed that the saturated solubility could depend not only on the pore size but also on the particle size of the nanocarriers. Moreover, with our resveratrol-mesoporous silica nanoparticles formulation, we have observed that the permeability of resveratrol encapsulated in MCM-48 nanoparticles (90 nm) can be enhanced compared to a resveratrol suspension when tested through the human colon carcinoma cell monolayer (Caco-2). Using an in vitro NF-κB assay, we showed that resveratrol encapsulation did not alter its bioactivity and, at lower concentration, i.e., 5 µg mL-1, resveratrol encapsulation provided higher anti-inflammatory activity compared to both resveratrol suspension and solution. All combined, the reported results clearly highlight the potential of small size mesoporous silica nanoparticles as next generation nanocarriers for hydrophobic drugs and nutraceuticals.

Effect of surface functionality of silica nanoparticles on cellular uptake and cytotoxicity.

Mesoporous silica nanoparticles (MCM-41) with different surface chemistry were used as carrier system to study its influence on drug delivery and anticancer activity of curcumin (CUR). CUR was encapsulated in pristine MCM-41 (hydrophilic and negatively charged), amino functionalized MCM-41 (MCM-41-NH2 which is hydrophilic and positively charged), and methyl functionalized MCM-41 (MCM-41-CH3 which is hydrophobic and negatively charged) and evaluated for in vitro release and cell cytotoxicity in human squamous cell carcinoma cell line (SCC25). Various techniques were employed to evaluate the performance of these materials on cellular uptake and anticancer activity in the SCC25 cell line. Both positively and negatively charged surfaces demonstrated enhanced drug release and anticancer activity compared to pure CUR. Positively charged nanoparticles showed higher cell uptake compared to negatively charged nanoparticles owing to its electrostatic interaction with cells. However, hydrophobic surface modified nanoparticles (MCM-41-CH3) showed no improvement in drug release and anticancer activity due to its poor wetting effect. Cell cycle analysis and cell apoptosis studies revealed different pathway mechanisms followed by the positively and negatively charged nanoparticles but exhibiting similar anticancer activity in SCC25 cells.

Cannabidiol - Help and hype in targeting mucosal diseases.

Cannabidiol (CBD) is one of the most commonly utilised phytocannabinoids due to its non-psychoactive and multiple potential therapeutic properties and its non-selective pharmacology. Recent studies have demonstrated efficacy of CBD in some types of drug resistant epilepsies in combination with other therapies; comparative efficacy to other agents or placebo has been hoped for anxiety, chronic pain, and inflammatory disorders based on animal data. Although CBD products are generally treated as a restricted substance, these are being eased, partially in response to significant growth in CBD product usage and increased production but more due to emerging evidence about its safety and pharmacological properties. Currently, only one CBD product (Epidiolex®) has been approved by the Australian Therapeutic Goods Administration and US Food and Drug Administration. CBD has demonstrated promise in alleviating gut and lung diseases in vitro; however, its physicochemical properties pose a significant barrier to achieving pharmacological effects in in vivo and clinical trials. Improving CBD formulations and delivery methods using technologies including self-emulsifying emulsion, nano and micro particles could overcome these shortfalls and improve its efficacy. This review focuses on the therapeutic potential of CBD in gastrointestinal and lung diseases from the available in vitro, in vivo, and clinical research. We report on identified research gaps and obstacles in the development of CBD-based therapeutics, including novel delivery methods.

Engineered smart materials for RNA based molecular therapy to treat Glioblastoma.

Glioblastoma (GBM) is an aggressive malignancy of the central nervous system (CNS) that remains incurable despite the multitude of improvements in cancer therapeutics. The conventional chemo and radiotherapy post-surgery have only been able to improve the prognosis slightly; however, the development of resistance and/or tumor recurrence is almost inevitable. There is a pressing need for adjuvant molecular therapies that can successfully and efficiently block tumor progression. During the last few decades, non-coding RNAs (ncRNAs) have emerged as key players in regulating various hallmarks of cancer including that of GBM. The levels of many ncRNAs are dysregulated in cancer, and ectopic modulation of their levels by delivering antagonists or overexpression constructs could serve as an attractive option for cancer therapy. The therapeutic potential of several types of ncRNAs, including miRNAs, lncRNAs, and circRNAs, has been validated in both in vitro and in vivo models of GBM. However, the delivery of these RNA-based therapeutics is highly challenging, especially to the tumors of the brain as the blood-brain barrier (BBB) poses as a major obstacle, among others. Also, since RNA is extremely fragile in nature, careful considerations must be met while designing a delivery agent. In this review we have shed light on how ncRNA therapy can overcome the limitations of its predecessor conventional therapy with an emphasis on smart nanomaterials that can aide in the safe and targeted delivery of nucleic acids to treat GBM. Additionally, critical gaps that currently exist for successful transition from viral to non-viral vector delivery systems have been identified. Finally, we have provided a perspective on the future directions, potential pathways, and target areas for achieving rapid clinical translation of, RNA-based macromolecular therapy to advance the effective treatment of GBM and other related diseases.

Clinical Translation of Extracellular Vesicles.

Extracellular vesicles (EVs) occur in a variety of bodily fluids and have gained recent attraction as natural materials due to their bioactive surfaces, internal cargo, and role in intercellular communication. EVs contain various biomolecules, including surface and cytoplasmic proteins; and nucleic acids that are often representative of the originating cells. EVs can transfer content to other cells, a process that is thought to be important for several biological processes, including immune responses, oncogenesis, and angiogenesis. An increased understanding of the underlying mechanisms of EV biogenesis, composition, and function has led to an exponential increase in preclinical and clinical assessment of EVs for biomedical applications, such as diagnostics and drug delivery. Bacterium-derived EV vaccines have been in clinical use for decades and a few EV-based diagnostic assays regulated under Clinical Laboratory Improvement Amendments have been approved for use in single laboratories. Though, EV-based products are yet to receive widespread clinical approval from national regulatory agencies such as the United States Food and Drug Administration (USFDA) and European Medicine Agency (EMA), many are in late-stage clinical trials. This perspective sheds light on the unique characteristics of EVs, highlighting current clinical trends, emerging applications, challenges and future perspectives of EVs in clinical use.

Silica nanoparticles for brain cancer.

INTRODUCTION: Brain cancer is a debilitating disease with a poor survival rate. There are significant challenges for effective treatment due to the presence of the blood-brain barrier (BBB) and blood-tumor barrier (BTB) which impedes drug delivery to tumor sites. Many nanomedicines have been tested in improving both the survival and quality of life of patients with brain cancer with the recent focus on inorganic nanoparticles such as silica nanoparticles (SNPs). This review examines the use of SNPs as a novel approach for diagnosing, treating, and theranostics of brain cancer. AREAS COVERED: The review provides an overview of different brain cancers and current therapies available. A special focus on the key functional properties of SNPs is discussed which makes them an attractive material in the field of onco-nanomedicine. Strategies to overcome the BBB using SNPs are analyzed. Furthermore, recent advancements in active targeting, combination therapies, and innovative nanotherapeutics utilizing SNPs are discussed. Safety considerations, toxicity profiles, and regulatory aspects are addressed to provide an understanding of SNPs' translational potential. EXPERT OPINION: SNPs have tremendous prospects in brain cancer research. The multifunctionality of SNPs has the potential to overcome both the BBB and BTB limitations and can be used for brain cancer imaging, drug delivery, and theranostics. The insights provided will facilitate the development of next-generation, innovative strategies, guiding future research toward improved diagnosis, targeted therapy, and better outcomes in brain cancer patients.

Virus-like Silica Nanoparticles Improve Permeability of Macromolecules across the Blood-Brain Barrier In Vitro.

The presence of the blood-brain barrier (BBB) limits the delivery of therapies into the brain. There has been significant interest in overcoming the BBB for the effective delivery of therapies to the brain. Inorganic nanomaterials, especially silica nanoparticles with varying surface chemistry and surface topology, have been recently used as permeation enhancers for oral protein delivery. In this context, nanoparticles with varying sizes and surface chemistries have been employed to overcome this barrier; however, there is no report examining the effect of nanoscale roughness on BBB permeability. This paper reports the influence of nanoscale surface roughness on the integrity and permeability of the BBB in vitro, using smooth surface Stöber silica nanoparticles (60 nm) compared to rough surface virus-like silica nanoparticles (VSNP, 60 nm). Our findings reveal that VSNP (1 mg/mL) with virus-mimicking-topology spiky surface have a greater effect on transiently opening endothelial tight junctions of the BBB than the same dose of Stöber silica nanoparticles (1 mg/mL) by increasing the FITC-Dextran (70 kDa) permeability 1.9-fold and by decreasing the trans-endothelial electrical resistance (TEER) by 2.7-fold. This proof-of-concept research paves the way for future studies to develop next-generation tailored surface-modified silica nanoparticles, enabling safe and efficient macromolecule transport across the BBB.

Nanobiomaterials to modulate natural killer cell responses for effective cancer immunotherapy.

Natural killer (NK) cells have emerged as a major target for cancer immunotherapies, particularly as cellular therapy modalities because they have relatively less toxicity than T lymphocytes. However, NK cell-based therapy suffers from many challenges, including problems with its activation, resistance to genetic engineering, and large-scale expansion needed for therapeutic purposes. Recently, nanobiomaterials have emerged as a promising solution to control the challenges associated with NK cells. This focused review summarises the recent advances in the field and highlights current and future perspectives of using nanobiomaterials to maximise anticancer responses of NK cells for safe and effective immunotherapy. Finally, we provide our opinion on the role of smart materials in activating NK cells as a potential cellular therapy of the future.

3D printing tablets for high-precision dose titration of caffeine.

Through 3D printing (3DP), many parameters of solid oral dosage forms can be customised, allowing for truly personalised medicine in a way that traditional pharmaceutical manufacturing would struggle to achieve. One of the many options for customisation involves dose titration, allowing for gradual weaning of a medication at dose intervals smaller than what is available commercially. In this study we demonstrate the high accuracy and precision of 3DP dose titration of caffeine, selected due to its global prevalence as a behavioural drug and well-known titration-dependent adverse reactions in humans. This was achieved using a simple filament base of polyvinyl alcohol, glycerol, and starch, utilising hot melt extrusion coupled with fused deposition modelling 3DP. Tablets containing 25 mg, 50 mg, and 100 mg doses of caffeine were successfully printed with drug content in the accepted range prescribed for conventional tablets (90 - 110%), and excellent precision whereby the weights of all doses showed a relative standard deviation of no more than 3%. Importantly, these results proved 3D printed tablets to be far superior to splitting a commercially available caffeine tablet. Additional assessment of filament and tablet samples were reviewed by differential scanning calorimetry, thermogravimetric analysis, HPLC, and scanning electron microscopy, showing no evidence of degradation of caffeine or the raw materials, with smooth and consistent filament extrusion. Upon dissolution, all tablets achieved greater than 70% release between 50 and 60 min, showing a predictable rapid release profile regardless of dose. The outcomes of this study highlight the benefits that dose titration with 3DP can offer, especially to more commonly prescribed medications that can have even more harmful withdrawal-induced adverse reactions.

Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model.

Besides the many advantages of oral drug administration, challenges like premature drug degradation and limited bioavailability in the gastro-intestinal tract (GIT) remain. A prolonged residence time in the GIT is beneficial for enhancing the therapeutic outcome when treating diseases associated with an increased intestinal clearance rate, like inflammatory bowel disease (IBD). In this study, we synthesized rod-shaped mesoporous silica nanoparticles (MSNs) functionalized with polyethylene glycol (PEG) or hyaluronic acid (HA) and investigated their bio-distribution upon oral administration in vivo. The negatively charged, non-toxic particles showed different accumulation behavior over time in healthy mice and in mice with dextran sulfate sodium (DSS)-induced intestinal inflammation. PEGylated particles were shown to accumulate in the lower intestinal tract of healthy animals, whereas inflammation promoted retention of HA-functionalized particles in this area. Overall systemic absorption was low. However, some particles were detected in organs of mice with DSS-induced colitis, especially in the case of MSN-PEG. The in vivo findings were connected to surface chemistry-related differences in particle adhesion on Caco-2/Raji and mucus-producing Caco-2/Raji/HT29 cell co-culture epithelial models in vitro. While the particle adhesion behavior in vivo was mirrored in the in vitro results, this was not the case for the resorption results, suggesting that the in vitro model does not fully reflect the erosion of the inflamed epithelial tissue. Overall, our study demonstrates the possibility to modulate accumulation and retention of MSNs in the GIT of mice with and without inflammation through surface functionalization, which has important implications for the formulation of nanoparticle-based delivery systems for oral delivery applications.

Silica nanoparticles: A review of their safety and current strategies to overcome biological barriers.

Silica nanoparticles (SNP) have gained tremendous attention in the recent decades. They have been used in many different biomedical fields including diagnosis, biosensing and drug delivery. Medical uses of SNP for anti-cancer, anti-microbial and theranostic applications are especially prominent due to their exceptional performance to deliver many different small molecules and recently biologics (mRNA, siRNA, antigens, antibodies, proteins, and peptides) at targeted sites. The physical and chemical properties of SNP such as large specific surface area, tuneable particle size and porosity, excellent biodegradability and biocompatibility make them an ideal drug delivery and diagnostic platform. Based on the available data and the pre-clinical performance of SNP, recent interest has driven these innovative materials towards clinical application with many of the formulations already in Phase I and Phase II trials. Herein, the progress of SNP in biomedical field is reviewed, and their safety aspects are analysed. Importantly, we critically evaluate the key structural characteristics of SNP to overcome different biological barriers including the blood-brain barrier (BBB), skin, tumour barrier and mucosal barrier. Future directions, potential pathways, and target areas towards rapid clinical translation of SNP are also recommended.

Spray nebulization enables polycaprolactone nanofiber production in a manner suitable for generation of scaffolds or direct deposition of nanofibers onto cells.

Spray nebulization is an elegant, but relatively unstudied, technique for scaffold production. Herein we fabricated mesh scaffolds of polycaprolactone (PCL) nanofibers via spray nebulization of 8% PCL in dichloromethane (DCM) using a 55.2 kPa compressed air stream and 17 ml h-1polymer solution flow rate. Using a refined protocol, we tested the hypothesis that spray nebulization would simultaneously generate nanofibers and eliminate solvent, yielding a benign environment at the point of fiber deposition that enabled the direct deposition of nanofibers onto cell monolayers. Nanofibers were collected onto a rotating plate 20 cm from the spray nozzle, but could be collected onto any static or moving surface. Scaffolds exhibited a mean nanofiber diameter of 910 ± 190 nm, ultimate tensile strength of 2.1 ± 0.3 MPa, elastic modulus of 3.3 ± 0.4 MPa, and failure strain of 62 ± 6%.In vitro, scaffolds supported growth of human keratinocyte cell epithelial-like layers, consistent with potential utility as a dermal scaffold. Fourier-transform infrared spectroscopy demonstrated that DCM had vaporized and was undetectable in scaffolds immediately following production. Exploiting the rapid elimination of DCM during fiber production, we demonstrated that nanofibers could be directly deposited on to cell monolayers, without compromising cell viability. This is the first description of spray nebulization generating nanofibers using PCL in DCM. Using this method, it is possible to rapidly produce nanofiber scaffolds, without need for high temperatures or voltages, yielding a method that could potentially be used to deposit nanofibers onto cell cultures or wound sites.

Virus-like silica nanoparticles enhance macromolecule permeation in vivo.

Nanoparticle based permeation enhancers have the potential to improve the oral delivery of biologics. Recently, solid silica nanoparticles were discovered to improve the intestinal permeability of peptides and proteins via transient opening of the gut epithelium. In this study, we have developed small-sized (∼60 nm) virus-like silica nanoparticles (VSNP) as a reversible and next generation non-toxic permeation enhancer for oral delivery of biologics. Our results show that the anionic VSNP showed a better permeation-enhancing effect than the same sized spherical Stöber silica nanoparticles (∼60 nm) by enhancing the apparent insulin permeability by 1.3-fold in the Caco-2 monolayer model and by 1.2-fold in the Caco-2/MTX-HT-29 co-culture model. In vivo experiments in healthy mice demonstrated that anionic VSNP significantly enhanced the permeation of fluorescently labelled 4 kDa dextran after oral administration compared to Stöber nanoparticles and positively charged VSNP. The results indicated that the nanoscale surface roughness is an important consideration when designing nanoparticle-based permeation enhancers. Overall, our study shows for the first time that small-sized (∼60 nm) VSNP with nanoscale surface roughness can be used as a non-toxic permeation enhancer for oral delivery of therapeutic peptides and proteins.