Selenium Nanoparticle Activity against S. mutans Biofilms as a Potential Treatment Alternative for Periodontitis.

The disruption of periodontal biofilms and prevailing antimicrobial resistance issues continue to pose a great challenge to the treatment of periodontitis. Here, we report on selenium nanoparticles (SeNPs) as a treatment alternative for periodontitis by determining their antibiofilm activity against S. mutans biofilms and the potential role of particle size in disrupting biofilms. SeNPs were synthesised via a reduction reaction. Various physicochemical characterisations were conducted on the NPs, including size and shape. The microbroth dilution method was used to conduct the biofilm and antibiofilm assay against S. mutans, which was analysed by absorbance. SeNPs displayed hydrodynamic sizes as low as 46 ± 4 nm at a volume ratio of 1:5 (sodium selenite/ascorbic acid) with good monodispersity and stability. Hydrodynamic sizes of SeNPs after resuspension in tryptic soy broth supplemented with 2.5% sucrose (TSB + 2.5% suc.) and incubated at 37 °C for 24 h, ranged from 112 to 263 nm, while the zeta potential values increased to greater than -11 mV. The biofilm assay indicated that S. mutans are weakly adherent, bordering on moderately adherent biofilm producers. The minimum biofilm inhibitory concentration (MBIC) was identified at 500 µg/mL. At a 1000 µg/mL concentration, SeNPs were able to inhibit S. mutan biofilms up to 99.87 ± 2.41% at a volume ratio of 1:1. No correlation was found between antibiofilm activity and particle size; however, antibiofilm activity was proven to be concentration-dependant. SeNPs demonstrate antibiofilm activity and may be useful for further development in treating periodontitis.

Injectable Thermoresponsive Hydrogels for Cancer Therapy: Challenges and Prospects.

The enervating side effects of chemotherapeutic drugs have necessitated the use of targeted drug delivery in cancer therapy. To that end, thermoresponsive hydrogels have been employed to improve the accumulation and maintenance of drug release at the tumour site. Despite their efficiency, very few thermoresponsive hydrogel-based drugs have undergone clinical trials, and even fewer have received FDA approval for cancer treatment. This review discusses the challenges of designing thermoresponsive hydrogels for cancer treatment and offers suggestions for these challenges as available in the literature. Furthermore, the argument for drug accumulation is challenged by the revelation of structural and functional barriers in tumours that may not support targeted drug release from hydrogels. Other highlights involve the demanding preparation process of thermoresponsive hydrogels, which often involves poor drug loading and difficulties in controlling the lower critical solution temperature and gelation kinetics. Additionally, the shortcomings in the administration process of thermosensitive hydrogels are examined, and special insight into the injectable thermosensitive hydrogels that reached clinical trials for cancer treatment is provided.

Molecule(s) of Interest: I. Ionic Liquids-Gateway to Newer Nanotechnology Applications: Advanced Nanobiotechnical Uses', Current Status, Emerging Trends, Challenges, and Prospects.

Ionic liquids are a potent class of organic compounds exhibiting unique physico-chemical properties and structural compositions that are different from the classical dipolar organic liquids. These molecules have found diverse applications in different chemical, biochemical, biophysical fields, and a number of industrial usages. The ionic liquids-based products and procedural applications are being developed for a number of newer industrial purposes, and academic uses in nanotechnology related procedures, processes, and products, especially in nanobiotechnology and nanomedicine. The current article overviews their uses in different fields, including applications, functions, and as parts of products and processes at primary and advanced levels. The application and product examples, and prospects in various fields of nanotechnology, domains of nanosystem syntheses, nano-scale product development, the process of membrane filtering, biofilm formation, and bio-separations are prominently discussed. The applications in carbon nanotubes; quantum dots; and drug, gene, and other payload delivery vehicle developments in the nanobiotechnology field are also covered. The broader scopes of applications of ionic liquids, future developmental possibilities in chemistry and different bio-aspects, promises in the newer genres of nanobiotechnology products, certain bioprocesses controls, and toxicity, together with emerging trends, challenges, and prospects are also elaborated.

Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair.

Optimal levels of functional recovery in peripheral nerve injuries remain elusive due to the architectural complexity of the neuronal environment. Commercial nerve repair conduits lack essential guidance cues for the regenerating axons. In this study, the regenerative potential of a biosimulated nerve repair system providing three types of regenerative cues was evaluated in a 10 mm sciatic nerve-gap model over 4 weeks. A thermo-ionically crosslinked gellan-xanthan hydrogel conduit loaded with electrospun PHBV-magnesium oleate-N-acetyl-cysteine (PHBV-MgOl-NAC) nanofibers was assessed for mechanical properties, nerve growth factor (NGF) release kinetics and PC12 viability. In vivo functional recovery was based on walking track analysis, gastrocnemius muscle mass and histological analysis. As an intraluminal filler, PHBV-MgOl-NAC nanofibers improved matrix resilience, deformation and fracture of the hydrogel conduit. NGF release was sustained over 4 weeks, governed by Fickian diffusion and Case-II relaxational release for the hollow conduit and the nanofiber-loaded conduit, respectively. The intraluminal fibers supported PC12 proliferation by 49% compared to the control, preserved up to 43% muscle mass and gradually improved functional recovery. The combined elements of physical guidance (nanofibrous scaffolding), chemical cues (N-acetyl-cysteine and magnesium oleate) and therapeutic cues (NGF and diclofenac sodium) offers a promising strategy for the regeneration of severed peripheral nerves.

Recent Advances in the Development of Antimicrobial and Antifouling Biocompatible Materials for Dental Applications.

The risk of secondary bacterial infections resulting from dental procedures has driven the design of antimicrobial and antifouling dental materials to curb pathogenic microbial growth, biofilm formation and subsequent oral and dental diseases. Studies have investigated approaches based primarily on contact-killing or release-killing materials. These materials are designed for addition into dental resins, adhesives and fillings or as immobilized coatings on tooth surfaces, titanium implants and dental prosthetics. This review discusses the recent developments in the different classes of biomaterials for antimicrobial and antifouling dental applications: polymeric drug-releasing materials, polymeric and metallic nanoparticles, polymeric biocides and antimicrobial peptides. With modifications to improve cytotoxicity and mechanical properties, contact-killing and anti-adhesion materials show potential for incorporation into dental materials for long-term clinical use as opposed to short-lived antimicrobial release-based coatings. However, extended durations of biocompatibility testing, and adjustment of essential biomaterial features to enhance material longevity in the oral cavity require further investigations to confirm suitability and safety of these materials in the clinical setting. The continuous exposure of dental restorative and regenerative materials to pathogenic microbes necessitates the implementation of antimicrobial and antifouling materials to either replace antibiotics or improve its rational use, especially in the day and age of the ever-increasing problem of antimicrobial resistance.

Design and characterisation of PHBV-magnesium oleate directional nanofibers for neurosupport.

The focus of significance in neuronal repair strategies is the design of scaffold systems capable of promoting neuronal regeneration and directional guidance via provision of a biomimetic environment resemblance of native neural tissue. The purpose of this study was to synthesize triple-cue electrospun aligned nanofibrous films (physical cue) of poly(3-hyroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) blended with magnesium-oleate (MgOl) (chemical cue) and N-acetyl-L-cysteine (NAC) (therapeutic cue) with potential incorporation into hollow nerve guidance conduits for an enhanced regenerative strategy. A Box-Behnken experimental design of 15 formulations, were analysed for crystallinity, textural properties and in vitro water-uptake, erosion, NAC-release and PC12 cell viability. Nucleating effects of MgOl provided tuning of PHBV electrospinning-induced crystallinity and mechanical properties. Tensile strengths and deformation moduli of ±12 MPa and ±7 MP, respectively, were attainable, thereby matching native nerve mechanics. Crystallinity changes ascribed differing release kinetics to NAC over 30 d: diffusion-based (42%-58% crystallinity with 33%-47% fractional release) and polymer-relaxational (59%-65% crystallinity with 60%-82% fractional release). The synergistic activity of MgOl and NAC increased PC12 proliferation by 32.6% compared to the control. MgOl produced dual actions as non-toxic plasticiser and PC12 cell proliferation-promoter via nucleation and neurotrophic-like effects, respectively. Controlled release of NAC imparted neuro-protectant effects on PC12 cells and promoted neurite extension, thus, making electrospun PHBV-MgOl nanofibrous films a versatile and promising approach for axonal guidance in peripheral nerve repair strategies.

Lipopolysaccharide Polyelectrolyte Complex for Oral Delivery of an Anti-tubercular Drug.

Anti-tuberculosis drug delivery has remained a challenge due to inconsistent bioavailability and inadequate sustained-release properties leading to treatment failure. To resolve these drawbacks, a lipopolysaccharide polyelectrolyte complex (PEC) encapsulated with rifampicin (RIF) (as the model drug) was fabricated, using the solvent injection technique (SIT), with soy lecithin (SLCT), and low-molecular-weight chitosan (LWCT). The average particle size and surface charge of RIF-loaded PEC particulates was 151.6 nm and + 33.0 nm, respectively, with noted decreased particle size and surface charge following increase in SLCT-LWCT mass ratio. Encapsulation efficiency (%EE) and drug-loading capacity (%LC) was 64.25% and 5.84%, respectively. Increase in SLCT-LWCT mass ratio significantly increased %EE with a marginal reduction in %LC. In vitro release studies showed a sustained-release profile for the PEC particulate tablet over 24 h (11.4% cumulative release) where the dominant release mechanism involved non-Fickian anomalous transport shifting towards super case II release as SLCT ratios increased (6.4% cumulative release). PEC-tablets prepared without SIT presented with rapid Fickian-diffusion-based drug release with up to 90% RIF release within 4 h. Ex vivo permeability studies revealed that lipopolysaccharide PEComplexation significantly increased the permeability of RIF by ~ 2-fold within the 8-h study period. These results suggest successful encapsulation of RIF within a PEC structure while imparting increased amorphic regions, as indicated by x-ray diffraction, for potential benefits in improved drug dissolution, bioavailability, and dosing.

Design and characterization of neurodurable gellan-xanthan pH-responsive hydrogels for controlled drug delivery.

OBJECTIVES: The purpose of this study was to develop novel, porous neurodurable interpenetrating networks of gellan-xanthan hydrogel conduits intercalated with pristine polymethyl methacrylate (PMMA) particles for the sustained and concurrent release of two model compounds: bovine serum albumin (BSA) and diclofenac sodium. METHODS: Hydrogel conduits were synthesized using a thermal-ionic crosslinking mechanism with direct incorporation of PMMA. The 15 formulations, generated using a Box-Behnken experimental design, were analyzed for drug release, swelling, erosion and textural properties. RESULTS: The 15 formulations provided a near zero-order release of BSA (37-75% fractional release) and diclofenac sodium (14-22% fractional release) over 20 and 30 days, respectively, modulated via a combination of pH-responsive (pH 7.4) dissolution of the intercalated pristine polymer particles and the unique gelling and erosion properties imparted by the graded addition of xanthan gum to the hydrogel blend. The concentration-dependent intercalation of PMMA extended drug release rates and enhanced matrix resilience from 31% to 56%. CONCLUSIONS: The gellan-xanthan ratio variability and the pore-inducing effects of intercalated PMMA yielded a means for fine tuning the mechanical attributes of the hydrogel matrices, particularly matrix rigidity and flexibility, offering an appealing strategy for the design and development of synthetic bioactive-releasing peripheral nerve repair conduits.

Design of chitospheres loaded with pristine polymer particles for extended drug delivery via polyelectrolyte complexation and particulate leaching.

The aim of this study was to investigate the drug release from swellable chitospheres laden with pristine polymethylmethacrylate (PMMA) nanoparticles. Chitosan matrices were prepared by sodium tripolyphosphate crosslinking from a chitosan suspension containing the model BCS class II drug, indomethacin. PMMA particles were added to the chitospheres as the modulator for drug release. Swelling and erosion studies in conjunction with textural profiling provided an understanding of the dominant and underlying drug release mechanisms of the ionically crosslinked chitospheres loaded with the pristine PMMA particles. A series of drug release studies performed in PBS pH 7.4 showed that the pristine particle-loaded chitospheres released indomethacin over 144 h in a first-order manner with 50% drug release occurring over 48 h. The study also revealed that in situ porogen leaching for pore creation and polyelectrolyte complex formation were the main mechanisms of release from the chitospheres. The results of this study may be utilized for the development of neuro-implants for controlled delivery of bioactives to the brain where scaffolds of superior mechanical strength and reduced swelling properties are required.

A review of bioactive release from nerve conduits as a neurotherapeutic strategy for neuronal growth in peripheral nerve injury.

Peripheral nerve regeneration strategies employ the use of polymeric engineered nerve conduits encompassed with components of a delivery system. This allows for the controlled and sustained release of neurotrophic growth factors for the enhancement of the innate regenerative capacity of the injured nerves. This review article focuses on the delivery of neurotrophic factors (NTFs) and the importance of the parameters that control release kinetics in the delivery of optimal quantities of NTFs for improved therapeutic effect and prevention of dose dumping. Studies utilizing various controlled-release strategies, in attempt to obtain ideal release kinetics, have been reviewed in this paper. Release strategies discussed include affinity-based models, crosslinking techniques, and layer-by-layer technologies. Currently available synthetic hollow nerve conduits, an alternative to the nerve autografts, have proven to be successful in the bridging and regeneration of primarily the short transected nerve gaps in several patient cases. However, current research emphasizes on the development of more advanced nerve conduits able to simulate the effectiveness of the autograft which includes, in particular, the ability to deliver growth factors.