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Dissolvable transdermal microneedles (μND) are promising micro-devices used to transport a wide selection of active compounds into the skin. To provide an effective therapeutic outcome, μNDs must pierce the human stratum corneum (~ 10 to 20 μm), without rupturing or bending during penetration, then release their cargo at the predetermined area and time. The ability of dissolvable μND arrays/patches to sufficiently pierce the skin is a crucial requirement, which depends on the material composition, μND geometry and fabrication techniques. This comprehensive review not only provides contemporary knowledge on the μND design approaches, but also the materials science facilitating these delivery systems and the opportunities these advanced materials can provide to enhance clinical outcomes. Refereed/Peer-reviewed

Current and future diagnostics urgently need imaging agents that are non-toxic and superior to clinically used small molecule dyes. Herein, we have developed luminescent green light-emitting carbon dots (GCDs) via a single-step hydrothermal reaction using a low-cost chemical precursor, p-toluenesulfonic acid. The GCDs exhibit excitation-independent fluorescence (FL) emission with the photoluminescence quantum yield of 70% and no FL quenching up to 1.25 mg/mL. The GCDs exhibit negligible cytotoxicity up to 250 µg/mL concentration in RAW 264.7 cells. Interestingly, GCDs exhibit an excitation-independent and concentration-dependent fluorescence emission behaviour. In vitro, the peak emission was obtained at 520 nm using the excitation at 430 nm. Whereas FL intensity increased with increasing concentration up to 1.25 mg/mL and a sharp decrease in FL intensity is observed upon further increasing the concentration of GCDs. Upon subcutaneously injecting the GCDs into a euthanized mouse, a similar concentration-dependent FL behaviour is evident. Background autofluorescence hinders the use of the GCDs at 420 nm excitation, however, a strong FL emission at 520 nm can be obtained by exciting subcutaneously injected GCDs at 465 nm—demonstrating excitation-independent emission characteristics. The above results indicate the potential of the non-toxic, low-cost carbon dots for diverse bioimaging applications. Graphical abstract Ultra-bright green-emitting carbon dots (GCDs) with photoluminescence quantum yield of 70% were synthesized using p-toluenesulfonic acid and ethylenediamine as precursors. The GCDs were subcutaneously injected into fresh mouse cadaver for fluorescence (FL)bioimaging, showing dose-dependent FL intensity behaviour.

In the current study, we have performed in-silicoresearch to explore the potential of a target protein against a set of existing known ligands and its analog. The protein structure was modeled as its complete structure was unavailable in the PDB databank and MD simulated for 50ns followed by its validation usingSAVES server (online tool).Some of the ligands used in the study were downloaded from the PubChem database while some were built using Molecule Builder ofSchrödinger 2022-2.The molecular docking was performed using the Glide module ofSchrödinger 2022-2. Further, the calculation of free energy of binding using the Prime module ofSchrödinger 2022-2 was performed. Encouraged by the results obtained from molecular docking and MM-GBSA calculation, we performed MD simulation of threeselected compounds using the DESMOND module. The uploaded file areas follows: 1. Modelled Protein Structure 2. Ligand structure (skc file) 3. Molecular Docking File 4. Molecular Docking of Querectinand its analog 5. MD Simulation Files &nbsp

Post-transition metal-based liquid alloys are emerging as media for undertaking chemical reactions.

Macromolecular therapeutics of biological origin, also known as biologics, have become one of the fastest-growing classes of drugs for management of a range of chronic and acute conditions. The majority of approved biologics are administered via the parenteral route and are thus expensive, have low patient compliance, and have high systemic toxicity. Therefore, tremendous efforts have been devoted to the development of carriers for oral delivery of biologics. This review evaluates key chemical (e.g. pH and enzymes) and physiological challenges to oral biologics delivery. We review the conventional formulation strategies and their limitations, followed by a detailed account of the progress on the use of nanocarriers used for oral biologics delivery, covering organic and inorganic nanocarriers. Lastly, we discuss limitations and opportunities presented by these emerging nanomaterials in oral biologics delivery.

Nanoparticle based permeation enhancers have the potential to improve oral delivery of biologics. Recently, solid silica nanoparticles were discovered to improve intestinal permeability of peptides and proteins via transient opening...

In the present study, a modified solvothermal reaction of (hematite) with titanium(IV) butoxide and gold(III) chloride produced ternary Au@TiO2/α-Fe2O3 nanocomposite. The designed Au@TiO2/α-Fe2O3 photocatalyst exhibits nanoring-like structure with high crystallinity indicating the possibility of manufacturing extreme structures and offering a new nanostructure that was not previously studied. Both TiO2 and Au nanoparticles (NPs) were found to be dispersed uniformly on the α-Fe2O3 surface. X-ray diffraction powder technique combined with X-ray photoelectron (XPS) and Raman spectroscopy confirm the formation of the three materials with cubic Au, anatase TiO2 and hematite α-Fe2O3 structures, respectively. The photocatalytic activity proves the performance of this ternary heterojunction to decomposes different pollutants. It was found that, TiO2 absorbs UV-light, α-Fe2O3 absorbs both UV and Visible light and plasmonic gold NPs work as an electron mediator and therefore exhalt the photocatalytic efficiency of the ternary Au@TiO2/α-Fe2O3 photocatalyst. The present work delivers a novel perception to develop a stable photocatalyst based metal oxide/noble-metal hetero-nanostructure for the degradation of different types of pollutants in the industrial zones.

Ketamine in sub-anaesthetic doses has analgesic properties and an opioid-sparing effect. Intrathecal (i.t.) delivery of analgesics bypasses systemic metabolism and delivers the analgesic agent adjacent to the target receptors in the spinal cord and so small doses are required to achieve effective pain relief. In order to relieve intractable cancer-related pain, sustained-release ketamine formulations are required in combination with a strong opioid because frequent i.t. injection is not practical. In this study, ketamine or ketamine-loaded porous silicon (pSi) were encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles by a novel supercritical carbon dioxide (scCO2) method, thereby avoiding the use of organic solvent. Multiple parameters including theoretical drug loading (DL), presence of pSi, size of scCO2 vessel, PLGA type, and use of co-solvent were investigated with a view to obtaining high DL and a sustained-release for an extended period. The most important finding was that the use of a large scCO2 vessel (60 mL) resulted in a much higher encapsulation efficiency (EE) compared with a small vessel (12 mL). In addition, pre-loading ketamine into pSi slightly improved the level of drug incorporation (i.e. EE and DL). Although the in vitro release was mainly affected by the drug payload, the use of the large scCO2 vessel reduced the burst release and extended the release period for PLGA microparticles with 10% or 20% ketamine loading. Together, our findings provide valuable information for optimization of drug delivery systems prepared with the aid of scCO2.

An increase in the number of multidrug-resistant microbial strains is the biggest threat to global health and is projected to cause >10 million deaths by 2055. The carbapenem family of antibacterial drugs are an important class of last-resort treatment of infections caused by drug-resistant bacteria and are only available as an injectable formulation. Given their instability within the gut and poor permeability across the gut wall, oral carbapenem formulations show poor bioavailability. Meropenem (MER), a carbapenem antibiotic, has broad-spectrum antibacterial activity, but suffers from the above-mentioned issues. In this review, we discuss strategies for improving the oral bioavailability of MER, such as inhibiting tubular secretion, prodrug formulations, and use of nanomedicine. We also highlight challenges and emerging approaches for the development of oral MER.

This article reports the synthesis of PbO doped MgZnO (PbO@MgZnO) by a co-precipitation method, followed by an ultrasonication process. PbO@MgZnO demonstrates a significant adsorption capability toward Magenta Dye (MD). The greatest adsorption capability was optimized by varying parameters such as pH, MD concentration, and adsorbent dose. The kinetics study illustrates that the adsorption of MD on PbO@MgZnO follows the pseudo-second-order. The isotherm study revealed that Langmuir is best fitted for the adsorption, but with little difference in the R2 value of Langmuir and Freundlich, the adsorption process cloud be single or multi-layer. The maximum adsorption capacity was found to be 333.33 mg/g. The negative ΔG refers to the spontaneity of MD adsorption on PbO@MgZnO. The steric parameters from statistical physics models also favor the multi-layer adsorption mechanism. As a function of solution temperature, the parameter n pattern has values of n = 0.395, 0.290, and 0.280 for 298, 308, and 318 K, respectively (i.e., all values were below 1). Therefore, horizontal molecule positioning and multiple locking mechanisms were implicated during interactions between MD and PbO@MgZnO active sites.

Meropenem (MER) is an effective broad-spectrum antibiotic currently only available in the parenteral form requiring frequent drug preparation and administration due to its extremely poor stability. The unavailability of oral Meropenem is primarily due to its ultrapoor handling and processing stability, hydrophilic nature that inhibits the passive diffusion across the gastrointestinal (GI) epithelium, degradation in the harsh gastric environment, and GI expulsion through enterocyte efflux glycoproteins. In this regard, we have developed an oral drug delivery system that confines MER into mesoporous silica nanoparticles (MSNs i.e, MCM-41 ∼141 nm) using a novel liquid carbon dioxide (CO2) method. MER was efficiently encapsulated within pristine, phosphonate (negatively charged MSN), and amine (positively charged MSN) modified MSNs with loading capacity ranging between 25 wt % and 31 wt %. Next, the MER-MCM-NH2 particles were electrostatically coated with Eudragit S100 enteric polymer that protected MER against gastric pH (pH 1.9) and enabled site-specific delivery in the small intestine (pH 6.8). Cellular uptake results in RAW 264.7 macrophage, Caco-2, and LS174T cells confirming the efficient cellular uptake of nanoparticles in all three cell lines. More importantly, the bidirectional transport (absorptive and secretory) of MER across Caco-2 monolayer was significantly improved for both MSN-based formulations, particularly MSNs coated with a polymer (Eud-MER-MCM-NH2) where permeability was significantly enhanced (∼2.4-fold) for absorptive transport and significantly reduced (∼1.8-fold) for secretory transport. Finally, in vitro antibacterial activity [minimum inhibitory concentration (MIC)] and time-kill assay against S. aureus and P. aeruginosa showed that drug-loaded nanoparticles were able to retain antibacterial activity comparable to that of free MER in a solution at equivalent dose. Thus, Eudragit-coated silica nanoparticles could offer a promising and novel solution for oral delivery of Meropenem and other such drugs.

The metformin perchlorate (MetH+·ClO4 −) with a new crystal structure was synthesized, characterized and comparatively studied with other metformin salts of Cl− and NO3 − by different spectroscopic techniques such as TGA-DSC and FT-IR as well as UV-visible spectroscopic studies. DFT calculations were performed by rwb97xd and 6-31G+(d,p) basis set for structure optimization and frequency calculations. Similar to MetH+·Cl−, the crystal packing of MetH+·ClO4 −andMetH+·NO3 − were stabilized by hexagonal hydrogen bond elongated network. The relative stability and reactivity of these salts were determined by exploring the DFT chemical descriptors such as chemical hardness, electronegativity, electronic chemical potential, electrophilicity and hardness. These calculations were employed to get the subset of variables that could categorize the metformin salts according to their reactivity.

Vancomycin (Van) is a key antibiotic of choice for the treatment of systemic methicillin resistant Staphylococcus aureus (MRSA) infections. However, due to its poor membrane permeability, it is administered parenterally, adding to the cost and effort of treatment. The poor oral bioavailability of Van is mainly due to its physico-chemical properties that limit its paracellular and transcellular transport across gastrointestinal (GI) epithelium. Herein we report the development of silica nanoparticles (SNPs)-based formulations that are able to enhance the epithelial permeability of Van. We synthesized SNPs of different pore sizes (2 nm and 9 nm) and modified their surface charge and polarity by attaching different functional groups (-NH2, -PO3, and -CH3). Van was loaded within these SNPs at a loading capacity in the range of ca. 18-29 wt%. The Van-loaded SNPs exhibited a controlled release behaviour when compared to un-encapsulated Van which showed rapid release due to its hydrophilic nature. Among Van-loaded SNPs, SNPs with large pores showed a prolonged release compared to SNPs with small pores while SNPs functionalised with -CH3 groups exhibited a slowest release among the functionalised SNPs. Importantly, Van-loaded SNPs, especially the large pore SNPs with negative charge, enhanced the permeability of Van across an epithelial cell monolayer (Caco-2 cell model) by up to 6-fold, with Papp values up to 1.716 × 10-5 cm s-1 (vs. 0.304 × 10-5 cm s-1 for un-encapsulated Van) after 3 h. The enhancement was dependent on both the type of SNPs and their surface functionalisation. The permeation enhancing effect of SNPs was due to its ability to transiently open the tight junctions measured by decrease in transepithelial resistance (TEER) which was reversible after 3 h. All in all, our data highlights the potential of SNPs (especially SNPs with large pores) for oral delivery of Van or other antimicrobial peptides.

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 β-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.

A newly synthesized zinc(II) complex, namely tert-butyl N-(2 mercaptoethyl)carbamatozinc(II) complex [Zn(Boc-S)(2)] (Boc = tert-butyl N-[2-mercaptoethyl]carbamate), has been used as an organozinc precursor for the production of crystalline ZnO and ZnO/TiO2 nanoparticles. The synthesized complex and the obtained nanomaterials were fully characterized using various spectroscopic and surface analysis techniques. Their surface morphology, chemical purity and stoichiometry have been investigated by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) as well as X-ray fluorescence. The synthesized Zn(II) molecular complex, ZnO and ZnO/TiO2 nanomaterials have been tested in alkaline aqueous solution (1.0 MNaOH) for the hydrogen evolution reaction (HER) using various electrochemical techniques. The results revealed high HER catalytic performance of ZnO and ZnO/TiO2 cathode materials, with the latter exhibiting higher catalytic activity recording an exchange current density (j(o)) of 0.3 mA cm(-2). This current value, which approaches that of Pt wire (0.5 mA cm(-2)), cross-sectional area similar to 0.008 cm(2), is about 11 and 100 times greater than those measured for ZnO alone (0.028 mA cm(-2)) and TiO2 alone (0.0032 mA cm(-2)), respectively. Moderate catalytic activity was recorded for the complex catalyst, namely GC-Zn(Boc-S)(2) with j(o) value of (0.01 mA cm(-2)). Tafel slope values of 130 and 122 mV dec(-1) were calculated for ZnO and ZnO/TiO2, respectively. Such Tafel slope values, which are close to that of the Pt wire (120 mV dec(-1)), referred to a Volmer-controlled HER kinetics. Other important electrochemical parameters describing the kinetics of the HER, such as roughness factor (R-f) and turnover frequency (TOF) were also estimated and discussed. The high numerical values of the various HER kinetic parameters recorded for the ZnO/TiO2 catalyst, in addition to its high stability and durability (stable for up to 10 000 continuous cathodic polarization cycles), besides maintaining its morphology and chemical composition after stability test (confirmed from SEM/EDX and XRD examinations), located it in a privileged position among the most efficient HER electrocatalysts reported in the literature.

Bacterial infections are a significant cause of mortality and morbidity worldwide, despite decades of use of numerous existing antibiotics and constant efforts by researchers to discover new antibiotics. The emergence of infections associated with antibiotic-resistant bacterial strains, has amplified the pressure to develop additional bactericidal therapies or new unorthodox approaches that can deal with antimicrobial resistance. Nanomaterial-based strategies, particularly those that do not rely on conventional small-molecule antibiotics, offer promise in part due to their ability to dodge existing mechanisms used by drug-resistant bacteria. Therefore, the use of nanomaterial-based formulations has attracted attention in the field of antibiotic therapy. In this Review, we highlight novel and emerging nanomaterial-based formulations along with details about the mechanisms by which nanoparticles can target bacterial infections and antimicrobial resistance. A detailed discussion about types and the activities of nanoparticles is presented, along with how they can be used as either delivery systems or as inherent antimicrobials, or a combination of both. Lastly, we highlight some toxicological concerns for the use of nanoparticles in antibiotic therapies.

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−1 polymer 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.

In this work, PdO/TiO and EuO/TiO nanocomposites (NCs) were synthesized using a new facile, template-free, and one-step solvothermal approach and characterized by several instrumentation techniques. X-ray photoelectron spectroscopy studies revealed the presence of oxidized form of the Pd and Eu nanoparticles within the NC materials (PdO and EuO). The two catalysts exhibited remarkable activity for the hydrogen evaluation reaction (HER) in a strong alkaline solution (4.0 M NaOH) with PdO/TiO catalyst being the best, which recorded an exchange current density (j) of 0.26 mA cm and a Tafel slope (β) of 125 mV dec. Such parameters are not far from those recorded for a commercial Pt/C catalyst (0.71 mA cm and 120 mV dec) performed here under the same operating conditions. EuO/TiO catalyst recorded j and β values of 0.05 mA cm and 135 mV dec. The Tafel slopes 125 and 135 mV dec calculated on the PdO/TiO and EuO/TiO catalysts suggest a HER kinetics controlled by the Volmer step. PdO/TiO catalyzed the HER with a high turnover frequency of 2.3 H/s at 0.2 V versus the reversible hydrogen electrode, while EuO/TiO catalyst only measured a turnover frequency value of 1.25 H/s at the same overpotential. The two catalysts exhibited excellent stability and durability after 10 000 cycles and 72 hours of controlled potential electrolysis at a high cathodic overpotential, reflecting their practical applicability. Scanning electron microscope and X-ray photoelectron spectroscopy examinations revealed that the morphology and chemistry of both catalysts were not altered as a result of the performed long-term stability and durability tests.

This work presents a modified solvothermal process for a facile synthesis of high thermally stable nanocrystalline anatase TiO2 NPs doped with Cu2O NPs. A Z-scheme mechanism was used to account for the enhanced photocatalytic activity exhibited by these materials. Also, the nanocomposite was impregnated in cotton fabric to obtain a modified fiber with high thermal stability, self-cleaning, enhanced UV protection, and antibacterial activity. The as-prepared nanomaterials and the coated fabric were characterized by various physicochemical techniques such as XRD, EDXRF, TGA, TEM, HRTEM, and SEM. The Cu2O/TiO2 molar ratio in the nanocomposite was found to possess a pronounced impact on the crystalline structure, size and morphology of TiO2 NPs. The XRD revealed proper substitutions of the few Ti4+ sites by Cu2+ ions in TiO2 host lattice. Optical measurements showed that the plasmonic peak of the Cu2O/TiO2 nanocomposite was affected by the copper-doping concentration, enhancing self-cleaning of Cu2O/TiO2 under direct sunlight. The TiO2/fiber self-cleaning efficiency (12 h for MB removal) was increased by the in situ growing of Cu2O (5.5 h). Antibacterial activity studies revealed high potential activity of Cu2O/TiO2 against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Kleissella pneumonia, Saccharomyces sp.) bacteria. The promising photocatalytic and biocidal activity of our synthesized Cu2O/TiO2 nanocomposites was ascribed to the reactive oxygen species generated by the Z-scheme mechanism under direct Sunlight.

PEGylation (i.e., attachment of polyethylene-glycol) of carbon nanotubes (CNTs) is one of the most widely used strategies to improve its biocompatibility and aqueous dispersion stability, which are critical for their successful clinical application. However, PEGylation of nanomaterials has recently been associated with production of anti-PEG antibody, low cellular uptake, and degradation. Herein, we explore surface functionalization of CNTs using the bovine-milk-derived protein succinylated β-lactoglobuline (Sblg) as an alternative strategy to PEGylation. The aqueous dispersion stability, in vitro cell uptake and biocompatibility of Sblg-functionalized multiwalled CNTs (Sblg-f-MWCNTs) was compared to PEGylated MWCNTs (PEG-f-MWCNTs). The surface functionalization with Sblg was found to improve the IC50 values of CNTs by ∼5- to 6-fold in comparison with pristine CNTs in various cell lines. Both Sblg-f-MWCNTs and PEG-f-MWCNTs improved the aqueous colloidal stability of CNTs, which remained suspended for a period of one month. Our study concluded that the Sblg provides a cost-effective alternative to the PEG-based CNT functionalization with significant improvement in the biocompatibility and dispersion stability of CNTs.

Mesopores silica nanotubes (MSNTs)-based chemical sensors for the rapid detection and of highly selective Fe

Ketamine in sub-anaesthetic doses has analgesic properties and an opioid-sparing effect. Intrathecal (i.t.) delivery of analgesics bypasses systemic metabolism and delivers the analgesic agent adjacent to the target receptors in the spinal cord and so small doses are required to achieve effective pain relief. In order to relieve intractable cancer-related pain, sustained-release ketamine formulations are required in combination with a strong opioid because frequent i.t. injection is not practical. In this study, ketamine or ketamine-loaded porous silicon (pSi) were encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles by a novel supercritical carbon dioxide (scCO

Coenzyme-Q10 (CoQ10) is a hydrophobic benzoquinone with antioxidant and anti-inflammatory properties. It is known to reduce oxidative stress in various health conditions. However, due to the low solubility, permeability, stability, and poor oral bioavailability, the oral dose of CoQ10 required for the desired therapeutic effect is very high. In the present study, CoQ10 is encapsulated into two milk derived proteins β-lactoglobulin and lactoferrin (BLG and LF) to produce self-assembled nanostructures of around 100-300 nm with high encapsulation efficiency (5-10% w/w). Both CoQ10-BLG and CoQ10-LF nanoparticles (NPs) significantly improved the aqueous solubility of CoQ10 60-fold and 300-fold, compared to CoQ10 alone, which hardly dissolves in water. Insight into the difference in solubility enhancement between BLG and LF was obtained using in silico modeling, which predicted that LF possesses multiple prospective CoQ10 binding sites, potentially enabling greater loading of CoQ10 on LF compared to BLG, which was predicted to be less capable of binding CoQ10. At pH 7.4, CoQ10-LF NPs showed a burst release between 30 min and 2 h then plateaued at 12 h with 30% of the total drug released over 48 h. However, pure CoQ10-BLG and pure CoQ10 had a significantly lower release rate with less than 15% and 8% cumulative release in 48 h, respectively. Most importantly, both BLG and LF NPs significantly improved CoQ10 permeability compared to the pre-dissolved drug across the Caco-2 monolayer with up to 2.5-fold apparent permeability enhancement for CoQ10-LF-further confirming the utility of this nanoencapsulation approach. Finally, in murine macrophage cells (J774A.1), CoQ10-LF NPs displayed significantly higher anti-ROS properties compared to CoQ10 (predissolved in DMSO) without affecting the cell viability. This study paves the way in improving oral bioavailability of poorly soluble drugs and nutraceuticals using milk-based self-assembled nanoparticles.

Coenzyme-Q10 (CoQ10) is a hydrophobic benzoquinone with antioxidant and anti-inflammatory properties. It is known to reduce oxidative stress in various health conditions. However, due to the low solubility, permeability, stability, and poor oral bioavailability, the oral dose of CoQ10 required for the desired therapeutic effect is very high. In the present study, CoQ10 is encapsulated into two milk derived proteins β-lactoglobulin and lactoferrin (BLG and LF) to produce self-assembled nanostructures of around 100-300 nm with high encapsulation efficiency (5-10% w/w). Both CoQ10-BLG and CoQ10-LF nanoparticles (NPs) significantly improved the aqueous solubility of CoQ10 60-fold and 300-fold, compared to CoQ10 alone, which hardly dissolves in water. Insight into the difference in solubility enhancement between BLG and LF was obtained using

Refereed/Peer-reviewed Epithelial surfaces protect exposed tissues in the body against intrusion of foreign materials, including xenobiotics, pollen and microbiota. The relative permeability of the various epithelia reflects their extent of exposure to the external environment and is in the ranking: intestinal≈ nasal ≥ bronchial ≥ tracheal > vaginal ≥ rectal > blood-perilymph barrier (otic), corneal > buccal > skin. Each epithelium also varies in their morphology, biochemistry, physiology, immunology and external fluid in line with their function. Each epithelium is also used as drug delivery sites to treat local conditions and, in some cases, for systemic delivery. The associated delivery systems have had to evolve to enable the delivery of larger drugs and biologicals, such as peptides, proteins, antibodies and biologicals and now include a range of physical, chemical, electrical, light, sound and other enhancement technologies. In addition, the quality-by-design approach to product regulation and the growth of generic products have also fostered advancement in epithelial drug delivery systems.

Meropenem (MER) is an effective broad-spectrum antibiotic currently only available in the parenteral form requiring frequent drug preparation and administration due to its extremely poor stability. The unavailability of oral Meropenem is primarily due to its ultrapoor handling and processing stability, hydrophilic nature that inhibits the passive diffusion across the gastrointestinal (GI) epithelium, degradation in the harsh gastric environment, and GI expulsion through enterocyte efflux glycoproteins. In this regard, we have developed an oral drug delivery system that confines MER into mesoporous silica nanoparticles (MSNs i.e, MCM-41 ∼141 nm) using a novel liquid carbon dioxide (CO

Herein, a multi-functional nano-in-micro hierarchical microsphere system is demonstrated for controlling the intestinal efflux pumps that affect the oral bioavailability of many therapeutic drugs. The hierarchical particles were generated by a co-flow microfluidic device and consisted of porous silica nanoparticles packed in Eudragit® polymeric matrix. Meropenem (MER), a last-resort antibacterial drug, was loaded into porous silica (MCM-48) with a loading capacity of 34.3 wt%. In this unique materials combination, MCM-48 enables ultrahigh loading of a hydrophilic MER, while the Eudragit® polymers not only protect MER from gastric pH but also act as an antagonist for p-glycoprotein protein efflux pumps to reduce the efflux of MER back into the gastrointestinal lumen. We investigated the in-vitro temporal MER release and bidirectional (absorptive and secretory) drug permeation model across the Caco-2 monolayer. The bioavailability of MER was significantly improved by all of the prepared formulations (i.e. increased absorptive transport and reduced secretory transport). The Eudragit® RSPO formulated MER-MCM showed the best performance with an efflux ratio (i.e. secretory transport/absorptive transport) of 0.35, which is 7.4 folds less than pure MER (2.62). Lastly, the prepared formulations were able to retain the antibacterial activity of MER against Staphylococcus aureus and Pseudomonas aeruginosa. Statement of significance Meropenem (MER) is a last resort antibiotic used for the treatment of drug-resistant and acute infections and only available as intravenous injectable dosage due to its poor chemical and thermal stability, and ultra-poor oral bioavailability because of the efflux action of P-glycoprotein (P-gp) pumps. Multifunctional colloidal micro/nanoparticles can help to solve these issues. Herein, we designed pomegranate-like hierarchical microspheres comprised of porous silica nanoparticles and enteric Eudragit® polymers (Eudragit®S100, Eudragit®RSPO, and Eudragit®RS100) using a co-flow microfluidic device. Our formulations allow for ultrahigh loading of hydrophilic MER, protects MER from gastric pH, and also block P-gp efflux pumps for enhanced MER permeation/retention with Eudragit®RSPO – showing 13.9-folds higher permeation and 7.4-folds reduction in efflux ratio in a bi-directional Caco-2 monolayer culture system.

Glioblastoma (GBM) is one of the most aggressive cancers of the brain. Despite extensive research over the last several decades, the survival rates for GBM have not improved and prognosis remains poor. To date, only a few therapies are approved for the treatment of GBM with the main reasons being: 1) significant tumour heterogeneity which promotes the selection of resistant subpopulations 2) GBM induced immunosuppression and 3) fortified location of the tumour in the brain which hinders the delivery of therapeutics. Existing therapies for GBM such as radiotherapy, surgery and chemotherapy have been unable to reach the clinical efficacy necessary to prolong patient survival more than a few months. This comprehensive review evaluates the current and emerging therapies including those in clinical trials that may potentially improve both targeted delivery of therapeutics directly to the tumour site and the development of agents that may specifically target GBM. Particular focus has also been given to emerging delivery technologies such as focused ultrasound, cellular delivery systems nanomedicines and immunotherapy. Finally, we discuss the importance of developing novel materials for improved delivery efficacy of nanoparticles and therapeutics to reduce the suffering of GBM patients.

We present a study on optical and surface chemistry engineering of nanoporous photonic crystals as sensing platforms for detection of ionic copper. The optical sensing system combines glutaraldehyde-crosslinked double-layered polyethyleneimine (PEI-GA-PEI)-functionalized nanoporous anodic alumina gradient-index filters (NAA-GIFs) with reflection spectroscopy for label-free, selective detection of ionic copper in water matrices. The spectral position of the photonic stopband (PSB) of PEI-GA-PEI-functionalized NAA-GIFs is tuned across the visible-NIR spectral region to assess the impact of this optical parameter on the sensing performance of the system. Spectral shifts in the characteristic PSB (ΔλPSB) of PEI-GA-PEI-functionalized NAA-GIFs upon exposure to analytical solutions of ionic copper are used as a sensing parameter. Shifts in ΔλPSB of these photonic crystals are monitored in real-time under dynamic flow conditions. Calibration of the sensing system with analytical solutions of ionic copper from 0.1 to 100 mM shows a dual sensing regime, at low (from 1 to 10 mM) and high (from 10 to 100 mM) concentrations, which is associated with conformational changes of the PEI-GA-PEI functional layer. The binding mechanism of Cu2+ in PEI-GA-PEI-modified NAA-GIFs follows a Freundlich isotherm model. The performance of the PEI-GA-PEI-NAA-GIFs for real-life applications is demonstrated using environmental water. The system shows excellent correlation in both environmental and analytical water solutions. This study provides new opportunities to engineer portable optical sensing systems with tailor-designed features to detect ionic copper for environmental applications.