Polymer-based Nanotherapeutics for Burn Wounds.

Burn wounds are complex and intricate injuries that have become a common cause of trauma leading to significant mortality and morbidity every year. Dressings are applied to burn wounds with the aim of promoting wound healing, preventing burn infection and restoring skin function. The dressing protects the injury and contributes to recovery of dermal and epidermal tissues. Polymer-based nanotherapeutics are increasingly being exploited as burn wound dressings. Natural polymers such as cellulose, chitin, alginate, collagen, gelatin and synthetic polymers like poly (lactic-co-glycolic acid), polycaprolactone, polyethylene glycol, and polyvinyl alcohol are being obtained as nanofibers by nanotechnological approaches like electrospinning and have shown wound healing and re-epithelialization properties. Their biocompatibility, biodegradability, sound mechanical properties and unique structures provide optimal microenvironment for cell proliferation, differentiation, and migration contributing to burn wound healing. The polymeric nanofibers mimic collagen fibers present in extracellular matrix and their high porosity and surface area to volume ratio enable increased interaction and sustained release of therapeutics at the site of thermal injury. This review is an attempt to compile all recent advances in the use of polymer-based nanotherapeutics for burn wounds. The various natural and synthetic polymers used have been discussed comprehensively and approaches being employed have been reported. With immense research effort that is currently being invested in this field and development of proper characterization and regulatory framework, future progress in burn treatment is expected to occur. Moreover, appropriate preclinical and clinical research will provide evidence for the great potential that polymer-based nanotherapeutics hold in the management of burn wounds.

Nano-lipidic formulation and therapeutic strategies for Alzheimer's disease via intranasal route.

AIM: The inability of drug molecules to cross the 'Blood-Brain Barrier' restrict the effective treatment of Alzheimer's disease. Lipid nanocarriers have proven to be a novel paradigm in brain targeting of bioactive by facilitating suitable therapeutic concentrations to be attained in the brain. METHODS: The relevant information regarding the title of this review article was collected from the peer-reviewed published articles. Also, the physicochemical properties, and their in vitro and in vivo evaluations were presented in this review article. RESULTS: Administration of lipid-based nano-carriers have abilities to target the brain, improve the pharmacokinetic and pharmacodynamics properties of drugs, and mitigate the side effects of encapsulated therapeutic active agents. CONCLUSION: Unlike oral and other routes, the Intranasal route promises high bioavailability, low first-pass effect, better pharmacokinetic properties, bypass of the systemic circulation, fewer incidences of unwanted side effects, and direct delivery of anti-AD drugs to the brain via circumventing 'Blood-Brain Barrier'.

3D Printing in Development of Nanomedicines.

Three-dimensional (3D) printing is gaining numerous advances in manufacturing approaches both at macro- and nanoscales. Three-dimensional printing is being explored for various biomedical applications and fabrication of nanomedicines using additive manufacturing techniques, and shows promising potential in fulfilling the need for patient-centric personalized treatment. Initial reports attributed this to availability of novel natural biomaterials and precisely engineered polymeric materials, which could be fabricated into exclusive 3D printed nanomaterials for various biomedical applications as nanomedicines. Nanomedicine is defined as the application of nanotechnology in designing nanomaterials for different medicinal applications, including diagnosis, treatment, monitoring, prevention, and control of diseases. Nanomedicine is also showing great impact in the design and development of precision medicine. In contrast to the "one-size-fits-all" criterion of the conventional medicine system, personalized or precision medicines consider the differences in various traits, including pharmacokinetics and genetics of different patients, which have shown improved results over conventional treatment. In the last few years, much literature has been published on the application of 3D printing for the fabrication of nanomedicine. This article deals with progress made in the development and design of tailor-made nanomedicine using 3D printing technology.

Optimization of Surfactant- and Cosurfactant-Aided Pine Oil Nanoemulsions by Isothermal Low-Energy Methods for Anticholinesterase Activity.

Highly stable pine oil-loaded nanoemulsions were evaluated for nutraceutical and storage stability applications. Pine oil-loaded nanoemulsion preparation was done with pine oil as the oily phase and additionally with different ratios of the non-ionic surfactant (Tween 80) and cosurfactant (ethanol) in an aqueous solution using the isothermal low-energy or spontaneous emulsification method. A transparent and stable nanoemulsion was obtained with a combination of pine oil (5 wt %), surfactant mixture (35 wt %), and water quantity sufficient (qs) by the isothermal low-energy method. The mean droplet size and ζ-potential of the fabricated nanoemulsion were ≈14 nm and -3.4 mV, respectively. The size of the transparent nanoemulsion increased to ∼45 nm and showed turbidity at 60 °C. Microrheological investigation highlighted the gel-sol-gel conversion in the presence of applied angular frequency at 25 °C. The loss modulus shifted to lower frequency at 60 °C in comparison to other temperatures. The anticholinesterase (AChE) inhibition activity of the pine oil-loaded nanoemulsion suggested a possible therapeutic value, and at 0.10% concentration of the nanoemulsion, the AChE inhibition activity was ≈95.72 ± 5.59%. These studies have important implications in fabrication and optimization of a nanoemulsion as a delivery system for combating reminiscence in Alzheimer's disease and application in the nutraceutical-based industry. This isothermal low-energy method offers an advantage of preparing an edible oil delivery system using simple and rapid operational parameters.

Formulation and optimization of silymarin-encapsulated binary micelles for enhanced amyloid disaggregation activity.

Silymarin (SLY) is a natural hydrophobic polyphenol that possesses antioxidant and amyloid fibril (Aß1-42) inhibition activity, but its activity is hindered due to low aqueous solubility. In this study, SLY is encapsulated in binary micelle (SLY-BM) that has been utilized to enhance the Aß1-42 fibril disaggregation. To enhance the aqueous solubility, SLY payload in micelles were optimized using Box-Behnken Design (BBD) to increase the efficiency of Aß1-42 fibril disaggregation. BBD was used to investigate the effect of ratio of Solutol HS15:Poloxamer-188, amount of acetone and hydration volume on critical quality attributes, particle size, and entrapment efficiency for SLY-BM. Furthermore, SLY-BM was characterized for its physical and drug release properties. The Aß1-42 fibril disaggregation and antioxidant studies were monitored using spectroscopic and microscopic techniques. BBD optimized the particle size <50 nm with %EE > 80%, and solubility factor of SLY-BM was enhanced to 460 folds than free SLY. Inhibitory concentration 50% (IC50) value of SLY-BM was 19.67 µg/mL compared to free SLY (30.06 µg/mL) in diphenylpicrahydrazyl assay. SLY-BM increased the Aß1-42 disaggregation compared to free SLY observed via thioflavin-T assay, photon correlation spectroscopy, and circular dichorism. Further morphological evaluation of Aß1-42 disaggregation was monitored by microscopy which showed that SLY-BM disaggregated the fibrils in 48 h. According to our findings, we concluded that SLY-BM micelles are potential candidates for delivery of neuroprotective agents.

Dye-Labeled Polyacryloyl Hydrazide-Ag Nanoparticle Fluorescent Probe for Ultrasensitive and Selective Detection of Au Ion.

The efficiency of a fluorescence sensing device based on metal-enhanced fluorescence (MEF) is dependent on the optimization of interaction between the fluorophore and the metal nanoparticle (NP). Herewith, ultrasensitive and selective turn-on sensing of Au3+ is achieved by using a suitable combination of fluorophore and metal NP system through sequential MEF effect. Dansyl hydrazide-tagged Ag NPs in the polyacryloyl hydrazide cavity are utilized to sense the picomolar concentration of Au3+ in aqueous media. We demonstrated that the selective Au3+ sensing is due to the selective deposition of Au on the Ag NP surface over the 16 other metal ions studied. The sensitivity is assigned to the strong overlapping of the emission band of the fluorophore with the surface plasmon band of the Au and improvement of fluorescence signal through successive MEF by Ag and Au colloids. The sensing is associated with a fivefold increase in fluorescence intensity and appearance of violet color of the solution. These luminescent Ag-Au bimetallic NPs may be utilized to trace cancer cells in biological systems and for cell imaging applications.

General Reagent Free Route to pH Responsive Polyacryloyl Hydrazide Capped Metal Nanogels for Synergistic Anticancer Therapeutics.

Herewith, we report a facile synthesis of pH responsive polyacryloyl hydrazide (PAH) capped silver (Ag) or gold (Au) nanogels for anticancer therapeutic applications. A cost-effective instant synthesis of PAH-Ag or PAH-Au nanoparticles (NPs) possessing controllable particle diameter and narrow size distribution was accomplished by adding AgNO3 or AuCl to the aqueous solution of PAH under ambient conditions without using any additional reagent. PAH possessing carbonyl hydrazide pendant functionality served as both reducing and capping agent to produce and stabilize the NPs. The stability analysis by UV-vis, dynamic light scattering, and transmission electron microscopy techniques suggested that these NPs may be stored in a refrigerator for at least up to 2 weeks with negligible change in conformation. The average hydrodynamic size of PAH-Ag NPs synthesized using 0.2 mmol/L AgNO3 changed from 122 to 226 nm on changing the pH of the medium from 5.4 to 7.4, which is a characteristic property of pH responsive nanogel. Camptothecin (CPT) with adequate loading efficiency (6.3%) was encapsulated in the PAH-Ag nanogels. Under pH 5.4 conditions, these nanogels released 78% of the originally loaded CPT over a period of 70 h. The antiproliferative potential of PAH-Ag-CPT nanogels (at [CPT]=0.6 µg/mL) against MCF-7 breast adeno-carcinoma cells were ∼350% higher compared to that of the free CPT as evidenced by high cellular internalization of these nanogels. Induction of apoptosis in MCF-7 breast adeno-carcinoma cells by PAH-Ag-CPT nanogels was evidenced by accumulation of late apoptotic cell population. Drug along with the PAH-Ag NPs were also encapsulated in a pH responsive hydrogel through in situ gelation at room temperature using acrylic acid as the cross-linker. The resulting hydrogel released quantitative amounts of both drug and PAH-Ag NPs over a period of 16 h. The simplicity of synthesis and ease of drug loading with efficient release render these NPs a viable candidate for various biomedical applications, and moreover this synthetic procedure may be extended to other metal NPs.

Polyacryloyl hydrazide: an efficient, simple, and cost effective precursor to a range of functional materials through hydrazide based click reactions.

Preparation and studies of ion exchangeable epoxy resins, stimuli responsive hydrogels, and polymer-dye conjugates have been accomplished through hydrazide based click reactions using polyacryloyl hydrazide (PAH) as the precursor. A convenient synthesis of PAH with quantitative functionality was achieved by treatment of polymethyl acrylate with hydrazine hydrate in the presence of tetra-n-butyl ammonium bromide. PAH was cured with bisphenol A diglycidyl ether (BADGE) at 60 °C to form transparent resins with superior mechanical properties (tensile strength = 2-40 MPa, Young's modulus = 3.3-1043 MPa, and ultimate elongation = 9-75%) compared to the conventional resins prepared using triethylene tetramine. The resins exhibited higher ion exchange capacities (1.2-6.3 mmol/g) compared to the commercial AHA ammonium-type (Tokuyama Co., Japan) membranes. An azo dye with aldehyde functionality was covalently attached to PAH through hydrazone linkage, and the dye labeled PAH exhibited colorimetric sensing ability for base and acids up to micromolar concentration. The swelling of the PAH based hydrogel varied in the range 4-450% depending on the pH and temperature of the medium. The hydrogels gradually released 30% of the original encapsulated dye in a period of 200 h. PAH-hydroxy naphthaldehyde conjugate released 75% of the original loading in ∼11 days at 37 °C and pH 5.0 through cleavage of the -CONHN═C- linkage. The study depicts the versatility of PAH as a precursor and inspires synthesis of a range of new materials based on PAH in the future.