Dissolvable sodium alginate-based antibacterial wound dressing patches: Design, characterization, and in vitro biological studies.

The treatment of infected wounds in patients with highly sensitive skin is challenging. Some of the available wound dressings cause further skin tear and bleeding upon removal thereby hindering the healing process. In this study, dissolvable antibacterial wound dressing patches loaded with cephalexin monohydrate were prepared from different amounts of sodium alginate (SA) and carboxymethyl cellulose (CMC) by the solvent casting evaporation technique. The patches displayed good tensile strength (3.83-13.83 MPa), appropriate thickness (0.09 to 0.31 mm) and good flexibility (74-98 %) suitable for the skin. The patches displayed good biodegradability and low moisture uptake suitable to prevent microbial invasion on the wound dressings upon storage. The release profile of the drug from the patches was sustained in the range of 47-80 % for 48 h, revealing their capability to inhibit bacterial infection. The biological assay showed that the patches did not induce cytotoxic effects on HaCaT cells, revealing good biocompatibility. The antimicrobial effect of the patches on the different strains of bacteria used in the study was significant. The cell migration (66.7-74.3 %) to the scratched gap was promising revealing the patches' capability to promote wound closure. The results obtained show that the wound dressings are potential materials for the treatment of infected wounds.

Hypothesis: Can drug-loaded platelets be used as delivery vehicles for blood-brain barrier penetration?

Neurovascular conditions are disorders associated with the blood vessels of the brain that are extremely difficult to treat successfully due to the selectivity and fastidious nature of the blood- brain barrier. Consequently, the efficacy of the pharmacological treatments for these conditions are greatly reduced thereby resulting in large amounts of neurovascular-related morbidity and mortality. Platelets are an important component of blood that actively respond to neurovascular distress in the body. Recent research has proven the effectiveness of platelets as drug delivery vehicles, during circumstances where the body naturally elicits a platelet response. This hypothesis highlights the theoretical use of platelets as drug delivery vehicles, able to penetrate the blood-brain barrier, for the treatment of two neurovascular conditions; glioblastoma multiforme and ischemic stroke. The success of the hypothesised system may lead to the development of a novel and extremely necessary delivery mechanism.

Synthesis and biocompatibility of dual-responsive thermosonic injectable organogels based on crosslinked N-(isopropyl acrylamide) for tumour microenvironment targeting.

A series of three dual-responsive 'thermosonic' (thermo- and ultrasound-responsive) injectable organogels (TIOs) based on crosslinked N-(isopropyl acrylamide) (NIPAM) bearing biocompatible polymeric constituents were investigated for strong gelation in response to tumour temperature, and sol-like fluid gel formation upon the application of an ultrasonic stimulus. A time-efficient free radical polymerisation reaction of ˂15 min resulted in TIO formation. Moreover, the formulation of the TIOs integrated green chemistry principles to ensure enhanced biocompatibility. Fourier Transform Infrared (FTIR) spectral analysis revealed the presence of new molecular vibrations at 847 and 771 cm-1 (CH deformation), which were indicative of the functionalisation of the NIPAM backbone with hydrophobic and ultrasound-responsive aromatic moieties. Thermo- and ultrasound-response analysis and rheological analysis demonstrated that the TIOs displayed a temperature-induced transition to a strong highly-structured gel, and an ultrasound-triggered increase in gel flowability dependant on the composition of the formulation. Cell proliferation studies were undertaken for the TIOs, which verified that the designed TIOs were all non-cytotoxic and promoted cell proliferation over 1, 3, and 5 day intervals. The rational design and formulation of a biocompatible injectable in-situ depot drug delivery system for ultimate application in tumour targeting was successfully achieved and warrant further investigation.

Design of a novel crosslinked HEC-PAA porous hydrogel composite for dissolution rate and solubility enhancement of efavirenz.

The purpose of this research was to synthesize, characterize and evaluate a Crosslinked Hydrogel Composite (CHC) as a new carrier for improving the solubility of the anti-HIV drug, efavirenz. The CHC was prepared by physical blending of hydroxyethylcellulose (HEC) with poly(acrylic acid) (PAA) (1:1) in the presence of poly(vinyl alcohol) (PVA) (as a crosslinker) (1:5) under lyophilization. Efavirenz was loaded in situ into the CHC in varying proportions (200-600 mg). The CHC demonstrated impressive rheological properties (dynamic viscosity=6053 mPa; 500 s(-1)) and tensile strength (2.5 mPa) compared with the native polymers (HEC and PAA). The physicochemical and thermal behavior also confirmed that the CHC was compatible with efavirenz. The incorporation of efavirenz in the CHC increased the surface area (4.4489-8.4948 m(2)/g) and pore volume (469.547-776.916Å) of the hydrogel system which was confirmed by SEM imagery and BET surface area measurements. The solubility of efavirenz was significantly enhanced (150 times) in a sustained release manner over 24h as affirmed by the in vitro drug release studies. The hydration medium provided by the CHC network played a pivotal role in improving the efavirenz solubility via increasing hydrogen bonding as proved by the zeta potential measurements (-18.0 to +0.10). The CHC may be a promising alternative as an oral formulation for the delivery of efavirenz with enhanced solubility.

Cur(Que)min: a neuroactive permutation of curcumin and quercetin for treating spinal cord injury.

Among Spinal Cord Injury (SCI) intervention the administration of high-dose high-potency steroidal drugs such as methylprednisolone or dexamethasone is used to reduce the inflammation associated with primary injury and prevention of the subsequent secondary injury. The administration of steroids has several side-effects that jeopardize their use and therefore safer chemical neuro-entities are required. Natural compounds such as curcumin (anti-oxidant) and quercetin (anti-inflammatory) have been investigated as alternative neuroactive, but are not as potent as the steroids. Hence, they are required in very high doses which may lead to significant toxicity causing an increase in cellular levels of reactive oxygen species, active iron chelation, inhibiting the activity of the cytochrome P450 enzymes such as glutathione-S-transferase and UDP-glucuronosyltransferase. A reduction in the dose of these neuroactives is possible with the administration of a 'chemically-variant' permutation with additive or synergistic therapeutic benefits. Therefore, we hypothesize that curcumin and quercetin, both natural polyphenolic flavonoids, can "additively and synergistically" improve the physiological outcome after traumatic SCI when used in combination and termed 'Cur(Que)min' - thereby decreasing the dose levels and hence reducing the inherent high dose-cytotoxicity of the individual neuroactives. This hypothesis provides the first-account of a curcumin-quercetin combination for SCI intervention theorizing the possible biomolecular-mechanism that may provide the scientific community with a novel neuroprotective and neurotherapeutic treatment option for SCI.

Vitamin D therapy and related metabolomics: is the calciferol dose and form the only requirements for successful clinical therapeutics?

A nutraceutical that has exploded onto the prescription pad in recent years is the fat soluble vitamin, vitamin D. This is due to an increasing medical interest in the utility of the vitamin in the treatment and prevention of an array of diseases and ailments. Despite the continued debate over the correct dose, form and serum levels, many clinicians fail to achieve intended therapeutic responses with their patients and deficiencies still exist. This may be due to medical professionals being less aware of the multitude of factors that can influence treatment when dosing a product. In this paper we explore the magnitude of interactions that exist between the host physiology and the vitamin and cite such points as a reason for confounding treatment end points. Aspects that are proposed to influence treatment success more critically than dose and molecular form prescribed are: organ pathology, intracellular states, the endocrine system, concomitant products, genetics, lifestyle, quality of product, and modern delivery systems.

Computational molecular modeling and structural rationalization for the design of a drug-loaded PLLA/PVA biopolymeric membrane.

The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 degrees C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.

Chemometric, physicomechanical and rheological analysis of the sol-gel dynamics and degree of crosslinking of glycosidic polymers.

The influence of calcium (Ca(2+)), zinc (Zn(2+)) and barium (Ba(2+)) ions on the sol-gel interconversion dynamics, degree of crosslinking and the matrix resilience of crosslinked alginate gelispheres was determined. The dependent compositional and operational variables of crosslinking make it a challenging task to optimize the degree of crosslinking and the physicomechanical properties of alginate gelispheres. The combinatory approach of textural profiling, assessing pertinent rheological descriptors and chemometric model analysis of the sol-gel interconversion mechanisms and energy paradigms involved during crosslinking, hydration and erosion of gelispheres was explored. Molecular structural modelling of the gelispheres provided a mechanistic understanding of the sol-gel interconversion phenomena and their influence on the degree of crosslinking, the hydrational dynamics and gelisphere formation. Rheological analysis revealed offset yield point values of 6.1 mg ml(-1) and 8.0 mg ml(-1) were computed from fitted regression curves for determining the crosslinker concentration required for combinatory crosslinkers such as Ca/Zn/Ba ions and Ba/Zn, respectively. The influence of hydration on the erosion was a direct function of the gelispheres physicomechanical strength. Textural profiling characterized the gelisphere matrices for their resilience. The various crosslinkers interacted with monomeric units at varying intensities. Ba-crosslinked gelispheres were brittle with dense polymeric networks. Zn-crosslinked gelispheres produced permeable resilient matrices when hydrated and Ca-crosslinked gelispheres demonstrated intermediate resilience with greater G/M ratio alginate grades. Chemometrical analysis explicated a potential link between several phenomena such as the type of crosslinkers employed, the static shear-rate viscosity attained, the matrix resilience and the associated sol-gel mechanisms and energy paradigms of crosslinked gelispheres.