A novel vaccine strategy against Brucellosis using Brucella abortus multi-epitope OMPs vaccine based on Lactococcus lactis live bacterial vectors.

Brucella infections typically occur in mucosal membranes, emphasizing the need for mucosal vaccinations. This study evaluated the effectiveness of orally administering Lactococcus lactis (L. lactis) for producing the Brucella abortus multi-epitope OMPs peptide. A multi-epitope plasmid was generated through a reverse vaccinology method, and mice were administered the genetically modified L. lactis orally as a vaccine. The plasmid underwent digestion, synthesizing a 39 kDa-sized protein known as OMPs by the target group. The sera of mice that were administered the pNZ8124-OMPs-L. lactis vaccine exhibited a notable presence of IgG1 antibodies specific to outer membrane proteins (OMPs), heightened levels of interferon (IFN-λ) and tumor necrosis factor alpha (TNF-α), and enhanced transcription rates of interleukin 4 (IL-4) and interleukin 10 (IL-10). The spleen sections from the pNZ8124-OMPs-L. lactis and IRIBA group had less morphological damage associated with inflammation, infiltration of lymphocytes, and lesions to the spleen. The findings present a novel approach to utilizing the food-grade, non-pathogenic L. lactis as a protein cell factory to synthesize innovative immunological candidate OMPs. This approach offers a distinctive way to evaluate experimental medicinal items' practicality, safety, affordability, and long-term sustainability.

The bioengineered and multifunctional nanoparticles in pancreatic cancer therapy: Bioresponisive nanostructures, phototherapy and targeted drug delivery.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Gellan gum fluid gels for topical administration of diclofenac.

Diclofenac topical formulations are often preferred for drug administration to patients who experience serious GIT problems. Absorption of the drug through the skin, however, can be challenging due to the natural protective feature of the stratum corneum (SC). In this article, fluid gels prepared from gellan gum were explored as a topical drug delivery vehicle. Rheological analysis of the formulations showed that it was possible to produce a topical gel with a viscosity and the mechanical strength similar to that of the commercially available Voltaren® gel using 1% w/w of a 50:50 low acyl/high acyl (LA/HA) gellan blend. Soft-tribology was used to assess the lubrication properties of gellan fluid gels. The lubrication of the gellan gum fluid gel formulations at high rubbing speeds was similar to the lubrication of the Voltaren® gel. The use of gellan gum dramatically increased skin permeation of diclofenac when compared with the commercially available formulation and could be controlled by changing the gellan gum concentration and/or sodium ion concentration in the formulation. This study highlights the potential use of fluid gels that can be easily tuned to have physical properties suitable for topical formulations with the added advantage of increasing drug permeation.

Drug release from E chemistry hypromellose tablets using the Bio-Dis USP type III apparatus: An evaluation of the effect of systematic agitation and ionic strength.

The aim of the study was to evaluate the effect of systematic agitation, increasing ionic strength and gel strength on drug release from a gel-forming matrix (HPMC E10M, E4M and E50LV) using USP type III Bio-Dis apparatus with theophylline as a model drug. The triboelectric charging; particle sizing, water content, true density and SEM of all the hypromellose grades, theophylline and formulated blends were characterised. The results showed that balanced inter-particulate forces exist between drug particles and the excipient surface and this enabled optimum charge to mass ratio to be measured. Agitation and ionic strength affected drug release from E50LV and E4M tablet matrices in comparison to the E10M tablet matrices. Drug release increased substantially when water was used as the dissolution media relative to media at pH 1.2 (containing 0.4M NaCl). The results showed all f2 values for the E10M tablet matrices were above 50 suggesting the drug release from these tablet matrices to be similar. Rheological data also explained the different drug release behaviour with the stress required to yield/erode being 1Pa, 150Pa, and 320Pa, for the E50LV, E4M and E10M respectively. The stiffness of the gel was also found to be varied from 2.5Pa, 176.2Pa and 408.3Pa for the E50LV, E4M and E10M respectively. The lower G' value can be explained by a softer gel being formed after tablet introduction into the dissolution media thereby indicating faster drug release.

Development of mucoadhesive sprayable gellan gum fluid gels.

The nasal mucosa provides a potentially good route for local and systemic drug delivery. However, the protective feature of the nasal cavity make intranasal delivery challenging. The application of mucoadhesive polymers in nasal drug delivery systems enhances the retention of the dosage form in the nasal cavity. Several groups have investigated using low acyl gellan as a drug delivery vehicle but only limited research however, has been performed on high acyl gellan for this purpose, despite its properties being more conducive to mucoadhesion. High acyl gellan produces highly elastic gels below 60°C which make it difficult to spray using a mechanical spray device. Therefore, in this study we have tried to address this problem by making fluid gels by introducing a shear force during gelation of the gellan polymer. These fluid gel systems contain gelled micro-particles suspended in a solution of un-gelled polymer. These systems can therefore behave as pourable viscoelastic fluids. In this study we have investigated the rheological behavior and mucoadhesion of fluid gels of two different types of gellan (high and low acyl) and fluid gels prepared from blends of high and low acyl gellan at a 50:50 ratio. The results demonstrated that by preparing fluid gels of high acyl gellan, the rheological properties were sufficient to spray through a standard nasal spray device. Moreover fluid gels also significantly enhance both high acyl and low acyl gellan mucoadhesion properties.

Evaluation of gellan gum fluid gels as modified release oral liquids.

Oral liquids are often preferred for drug administration to patients for whom swallowing is difficult, however, formulating modified release versions can be challenging. A potential route to achieve modified release in oral liquids is by using fluid (sheared) gels formed by introducing a shear field during gelation in gel-forming biopolymers. These fluid gels can act as pourable viscoelastic fluids but retain true gel micro/nano structure. Here, we have demonstrated that fluid gels have potential as paediatric oral liquids preventing release of ibuprofen in simulated gastric fluid. Subsequent release at pH 7.4 was affected by the duration of exposure and magnitude of acid pH with a linear relationship between onset of release and the preceding acidic exposure duration. Delayed release was a result of increasing gel stiffness, a consequence of the acidity of the initial release media and exposure time. A much faster release rate was measured when exposure time in acid was 10 min compared with 60 min. This study highlights the potential to design fluid gels that are tuned to have a specified stiffness at a particular pH and exposure time. This could enable the preparation oral liquids with modified release behaviour.