Polyhydroxybutyrate (PHB) in nanoparticulate form improves physical and biological performance of scaffolds.

Polyhydroxyalkanoates (PHAs) are natural polyesters produced by microorganisms as a source of intracellular energy reserves. Due to their desirable material characteristics, these polymers have been thoroughly investigated for tissue engineering and drug delivery applications. A tissue engineering scaffold serves as a substitute of the native extracellular matrix (ECM) and plays a crucial role in tissue regeneration by providing temporary support for cells during natural ECM formation. In this study, porous, biodegradable scaffolds were prepared using native polyhydroxybutyrate (PHB) and PHB in nanoparticulate form using salt leaching method, to investigate the differences in the physicochemical properties such as crystallinity, hydrophobicity, surface morphology, roughness, and surface area and biological properties of the prepared scaffolds. As per the BET analysis, PHB nanoparticles-based (PHBN) scaffolds presented a significant difference in the surface area as compare to PHB scaffolds. PHBN scaffolds showed decreased crystallinity and improved mechanical strength as compared to PHB scaffolds. Thermogravimetry analysis shows delayed degradation of PHBN scaffolds. An examination of Vero cell lines' cell viability and adhesion over time revealed enhanced performance of PHBN scaffolds. Our research suggests that scaffold made of PHB nanoparticles could serve as a superior material for tissue engineering applications than its native form.

Double and quadruple deletion mutant of EHV-1 is highly attenuated and induces optimal immune response.

Equid alphaherpesvirus 1 (EHV-1) infection causes significant health problems in equines. The EHV-1 infection leads to abortion storm in mares, respiratory disease and myeloencephalopathy. Despite the wide use of vaccines, the outbreaks of EHV-1 infections keep occurring globally, suggesting the need for the development of improved vaccines. Gene deletion attenuated mutant viruses could be a good candidate for the development of modified live vaccines. Here, we report the generation of mutant EHV-1 by deleting virulence (glycoprotein E & internal repeat 6; IR6) and immune evasive (pUL43 & pUL56) associated genes either individually or in combinations; and comprehensive evaluation of mutants through in vitro characterization followed by in vivo study in murine model to adjudge the attenuation of the virus and immune responses generated by mutants vis-à-vis wild type (wt) virus. The EHV-1 mutants with deletion of IR6 and gE genes (vToH-DMV) and four genes (i.e., gE, IR6, pUL43 and pUL56) (vToH-QMV) revealed a significant reduction in plaque size with minimal loss in replication efficiency in comparison to the wt virus. Further, in vivo studies showed virus attenuation adjudged through significant reduction in clinical signs, weight loss, gross and histopathological lesions in comparison to wt virus also revealed improved immune responses estimated through serum neutralization and flow cytometric analysis of CD4 + and CD8 + cell populations. Thus it can be concluded that EHV-1 mutants viz. vToH-DMV and vToH-QMV (novel combination) are promising vaccine candidates and qualify to be studied for adjudging the protective efficacy with wt virus challenge.

Anti-Inflammatory Therapeutics: Conventional Concepts and Future with Nanotechnology.

Anti-inflammatory therapies currently in use mainly include steroidal and non-steroidal drugs. Contrary to their side effects, the steroid hormones glucocorticoids, which are synthetic versions of natural cortisol, are nevertheless often employed to treat a variety of inflammatory disorders. Other drug class of choice is non-steroidal drugs which mainly target COX-2 and hence the synthesis of prostaglandins, particularly PGE2. To cure both the short-term effects of chronic inflammatory disorders and the long-term symptoms of acute inflammation, pharmaceutical chemists are in continuous search for more potent and less toxic agents. Apart from these two drug classes, phytochemicals are gaining the attention of researchers as source of alternative antiinflammatory agents. However, every drug class has its own advantages or disadvantages thus requiring intervention of newer approaches. Currently, drugs used for anti-inflammatory therapies are costly with low efficacy, high health risk, and socio-economic impact due to the concern issue of their toxicity. Recently, nano-drug delivery system has been experiencing main interest as a new approach for targeting therapeutic agents to the target sites in a controlled, sustained manner and has various advantages as compared to the conventional drug delivery system like, increased solubility, bioavailability, improved pharmacokinetic profile of drugs, surface area and rate of dissolution and additionally, overcomes the problems related to hydrophobicity, toxicity. Present review summarized the intervention of nanotechnology to overcome the limitations/ risk associated with current anti-inflammatory drugs of different classes.

Recent Progress in the Hesperetin Delivery Regimes: Significance of Pleiotropic Actions and Synergistic Anticancer Efficacy.

BACKGROUND: In the plant kingdom, flavonoids are widely distributed with multifunctional immunomodulatory actions. Hesperetin (HST) remains one of the well-studied compounds in this domain, initially perceived in citrus plants as an aglycone derivative of hesperidin (HDN). OBSERVATIONS: Natural origin, low in vivo toxicity, and pleiotropic functional essence are the foremost fascinations for HST use as an anticancer drug. However, low aqueous solubility accompanied with a prompt degradation by intestinal and hepatocellular enzymes impairs HST physiological absorption. MOTIVATION: Remedies attempted herein comprise the synthesis of derivatives and nanocarrier (NC)-mediated delivery. As the derivative synthesis aggravates the structural complexity, NC-driven HST delivery has emerged as a sustainable approach for its sustained release. Recent interest in HST has been due to its significant anticancer potential, characterized via inhibited cell division (proliferation), new blood vessel formation (angiogenesis), forceful occupation of neighboring cell's space (invasion), migration to erstwhile physiological locations (metastasis) and apoptotic induction. The sensitization of chemotherapeutic drugs (CDs) by HST is driven via stoichiometrically regulated synergistic actions. Purpose and Conclusion: This article sheds light on HST structure-function correlation and pleiotropic anticancer mechanisms, in unaided and NC-administered delivery in singular and with CDs synergy. The discussion could streamline the HST usefulness and long-term anticancer efficacy.

Scaffolds the backbone of tissue engineering: Advancements in use of polyhydroxyalkanoates (PHA).

Our body is built to heal from inside out naturally but wide-ranging medical conditions necessitate the need for artificial assistance, and therefore, something that can assist the body to heal wounds and damaged tissues quickly and efficiently is of utmost importance. Tissue engineering technology helps to regenerate new tissue to replace the diseased or injured one. The technology uses biodegradable porous three-dimensional scaffolds for mimicking the structure and functions of the natural extracellular matrix. The material and design of scaffolds are critical areas of biomaterial research. Biomaterial-based three-dimensional structures have been the most promising material to serve as scaffolds for seeding cells, both in vivo and in vitro. One such material is polyhydroxyalkanoates (PHAs) which are thermoplastic biopolyesters that are highly suitable for this purpose due to their enhanced biocompatibility, biodegradability, thermo-processability, diverse mechanical properties, non-toxicity and natural origin. Moreover, they have tremendous possibilities of customization through biological physical and chemical modification as well as blending with other materials. They are being used for several tissue engineering applications such as bone graft substitute, cardiovascular patches, stents, for nerve repair and in implantology as valves and sutures. The present review overviews usage of a multitude of PHA-based biomaterials for a wide range of tissue engineering applications, based on their properties suitable for the specific applications.

Ketoconazole encapsulated in chitosan-gellan gum nanocomplexes exhibits prolonged antifungal activity.

The objective of the present study was to prepare ketoconazole loaded chitosan-gellan gum (CSGG) nanoparticles and to evaluate them for antifungal activity against Aspergillus niger. Ketoconazole loaded CSGG nanoparticles were prepared by electrostatic complexation technique using chitosan (CS) as cationic polymer and gellan gum (GG) as anionic polymer with ketoconazole as drug. It was observed that the effect of gellan gum on particle size was more pronounced in comparison to chitosan and increase in its concentration resulted in a significant increase in particle size but decrease in zeta potential. Whereas, increase in concentration of chitosan resulted in increase in zeta potential. The particle size and zeta potential of optimal formulation was 155.7±26.1nm and 32.1±2.8mV which obtained at concentration of chitosan (0.02% w/v) and gellan gum (0.01% w/v). On comparative evaluation, ketoconazole loaded CSGG nanoparticles showed significantly higher antifungal activity against Aspergillus niger than dummy CSGG nanoparticles (without drug) and drug individually.

Enhancement of anti-inflammatory activity of glycyrrhizic acid by encapsulation in chitosan-katira gum nanoparticles.

Efforts were made to improve the bioavailability and efficacy of Glycyrrhizic acid, a triterpentine saponin obtained from Glycyrrhiza glabra, having several pharmacological properties, by its encapsulation in biocompatible biopolymeric nanoparticles. Polycationic chitosan and polyanionic gum katira were used to prepare nanoparticles by ionic complexation method. Glycyrrhizic acid was loaded into the nanoparticles and was then examined for change in its in vivo anti-inflammatory activity against carrageenan-induced rat hind paw inflammation. The effects of concentrations of glycyrrhizic acid, chitosan and katira gum, upon particle size and encapsulation efficiency of glycyrrhizic acid were studied with the help of response surface methodology employing 3-factor, 3-level central composite experimental design. Particle size and encapsulation efficiency of optimized nanoparticulate formulation were 175.8nm and 84.77%, respectively. Particles were observed in transmission electron microscopy to be spherical in shape and 80nm in size. FTIR analysis indicated electrostatic interactions between carboxyl groups of ammonium glycyrrhizinate and amino groups of chitosan. In vitro drug release studies indicated that glycyrrhizic acid was released from the nanoparticles following zero-order kinetics and that there was a sustained release of the drug with 90.71% of it being released over a 12h period, and that the mechanism of release of glycyrrhizic acid from the nanoparticles was a combination of diffusion and erosion of the polymer matrix. In-vivo anti inflammatory efficacy of glycyrrhizic acid clearly improved upon encapsulation in chitosan-katira gum nanoparticles, by overcoming the limited bioavailability of its other forms.

Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles.

Bromelain-loaded katira gum nanoparticles were synthesized using 3 level optimization process and desirability approach. Nanoparticles of the optimized batch were characterized using particle size analysis, zeta potential, transmission electron microscopy and Fourier-transform infrared spectroscopy. Investigation of their in vivo anti-inflammatory activity by employing carrageenan induced rat-paw oedema method showed that encapsulation of bromelain in katira gum nanoparticles substantially enhanced its anti-inflammatory potential. This may be attributed to enhanced absorption owing to reduced particle size or to protection of bromelain from acid proteases.

Alginate/gum acacia bipolymeric nanohydrogels--promising carrier for zinc oxide nanoparticles.

Zinc oxide nanoparticles (ZnO nps) are known to be effective against a wide array of microorganisms. At nanoscale, they have higher toxicity and they need to be rendered less toxic and more biocompatible. To achieve this, ZnO nps were incorporated in nanohydrogel particles made out of sodium alginate/gum acacia and cross-linker glutaraldehyde in order to ensure their gradual and sustained release instead of burst release, and hence lowering their toxicity. The particles synthesized were in the nano-range, i.e., 70-100 nm size and their in vitro release studies indicated that release of upto 68% of ZnO nps was prolonged to over 2 weeks following the Higuchi model. Cytotoxicity studies on vero cell line (African green monkey kidney cell line) revealed that toxicity of ZnO nps-loaded nanohydrogels was substantially lower as compared to ZnO nps. At the same time, it demonstrated desired level of antibiotic activity against Pseudomonas aeruginosa, an antibiotic resistant microbial model. In conclusion, this work led to successful preparation of novel formulation of ZnO incorporated in nanohydrogels that are not only safer but also retain adequate antibacterial activity due to their ability for gradual and sustained release of the active constituent.