Pharmaceutical Nanotechnology - Volume 8, Issue 1, 2020

In spite of the progress of conventional vaccines, improvements are required due to concerns about the low immunogenicity of the toxicity, instability, and the need for multiple administrations of the vaccines. To overcome the mentioned problems, nanotechnology has recently been incorporated into vaccine development. Nanotechnology increasingly plays an important role in vaccine development nanocarrier-based delivery systems that offer an opportunity to increase the cellular and humoral immune responses. The use of nanoparticles in vaccine formulations allows not only enhanced immunogenicity and stability of antigen, but also targeted delivery and slow release. Over the past decade, nanoscale size materials such as virus-like particles, liposomes, ISCOMs, polymeric, inorganic nanoparticles and emulsions have gained attention as potential delivery vehicles for vaccine antigens, which can both stabilize vaccine antigens and act as adjuvants. This advantage is attributable to the nanoscale particle size, which facilitates uptake by Antigen- Presenting Cells (APCs), then leading to efficient antigen recognition and presentation. Modifying the surfaces of nanoparticles with different targeting moieties permits the delivery of antigens to specific receptors on the cell surface, thereby stimulating selective and specific immune responses. This review provides an overview of recent advances in nanovaccinology.

Solid lipid particles have a great potential in sustained drug delivery, the lipid excipients are solid at room temperature with a slow degradation rate. Poly (D, L-lactic-coglycolic acid) (PLGA) has been successfully clinically applied for the sustained delivery of peptide drugs. A recent study showed the advantage of hybrid PLGA-lipid microparticles (MPs) over PLGA MPs for the sustained delivery of peptide drug in vivo. In this paper, we briefly present PLGA MPs, solid lipid MPs and PLGA lipid hybrid MP prepared by the double emulsion method and the spray drying method and discuss the effects of excipients on encapsulation efficiency of protein and peptide drugs in the MPs. The pros and cons of PLGA MPs, solid lipid MPs and PLGA lipid hybrid MP as carriers for sustained delivery of protein and peptide drugs are also discussed.

Background: Ciprofloxacin free base is practically insoluble in aqueous medium (0.0011 and 0.09 mg/mL at 25 and 37°C respectively). Its inorganic salt form (ciprofloxacin hydrochloride) is more soluble in water (1.35 mg/mL) however when administered orally, it exhibits decreased solubility in the stomach due to common ion effects. Ciprofloxacin free base was used in this study because of its greater hydrophobicity than its hydrochloride salt, which is required for effective permeability and potent antibacterial activity. Objective: The purpose of this study is to enhance oral solubility and bacterial cell permeability of the free base ciprofloxacin (CPX) using a single step CPX-chitosan (CT) selfassembly to form nanoplexes with organic counterions. It was envisioned that this would allow the delivery of larger amounts of active drug into the microorganisms. Methods: Ciprofloxacin-chitosan nanocomplex (nanoplex) was prepared using low energy electrostatic self-assembly technique previously described. Formation of eutectic nanoplex was confirmed using FTIR, DSC, TGA and SEM. The saturated solubility, in vitro release kinetics and mechanism of drug release were determined using mathematical models. Potency and synergism were determined from the inhibition zones, minimum inhibitory concentration (MIC) and Fractional Inhibitory Concentration (FIC) of the nanoplexes using Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Results: Formation of CPX-CT eutectic adduct polymeric nanoplexes was confirmed with FT-IR and DSC and SEM revealed the conversion of rod-like crystals of CPX (117 μm long) into spherical nanostructures (23-503 nm) dictated by pH, ionic strength and concentration of CT. The solubility of free base CPX increased to a maximum of 32.77 mg/mL compared to 0.0011-0.09 mg/mL reported in literature and dissolution efficiency increased to a maximum of 100% within 72 h. The synergistic effect of CT on antimicrobial activity of CPX was quantified, for the first time, using Fractional Inhibitory Concentration (FIC) of the nanoplexes. FIC was less than 0.5 in both Gram positive (0.031-0.250) and Gram negative (0.036-0.281) microorganisms used in this study, confirming synergistic enhancement of antimicrobial efficacy of CPX. Conclusion: It is evident that the design of drug-polymer nanocomplex formulation provides a platform for the synergistic enhancement of therapeutic potency of antibiotics.

Background: Curcumin has been used as a traditional medicine showing antiinflammatory, antimicrobial, and antiviral properties. Despite the promising potentials, curcumin-based drug development is hindered due to its poor solubility and cell uptake. Objective: This study aims to produce curcumin nanoemulsion (nanocurcumin) and evaluate its physical characteristics and in vitro cell cytotoxicity and antiviral activity against dengue virus (DENV). Methods: Nanocurcumin was generated by self-nanoemulsion technique. Cytotoxicity was determined using MTT assay in A549 cell line. Anti-DENV properties were determined by calculation of inhibitory concentration 50 (IC50) and plaque assay. Results: The resulting nanoemulsion showed uniform droplet size distribution with the average droplet size of 40.85 ± 0.919 nm. Nanocurcumin exhibited higher cell cytotoxicity compared to curcumin solution and may be explained by better cell uptake. Nanocurcumin treatment suppressed DENV growth, although no significant difference observed compared to the curcumin solution counterpart. Greater virus reduction was observed for DENV-1 and DENV-2. Conclusion: The synthesis of nanocurcumin improved curcumin physicochemical properties with potential as antiviral against DENV.

Background: Type 1 diabetes mellitus is characterized by the destruction of insulin- producing Beta cells in the pancreas. Researchers hope that islet transplantation will help to patients with insulin-dependent diabetes mellitus (IDDM). Oxidative stress is the most important challenge that beta cells face to it after isolation, and mitochondrial dysfunction is a crucial mediator in beta cells death. Hence, therapeutic approaches can shift to antioxidants through the application of nanoparticles such as cerium and yttrium oxide nanoparticles (Cer and Ytt Ox NPs) and nano-selenium (Nan Se). Objective: This study evaluates the effects of Cer and Ytt Ox NPs and Nan Se on H2O2- induced oxidative stress in pancreatic beta cells with focus on mitochondrial dysfunction pathway. Methods: CRI-D2 beta-cell line were pretreated with Cer Ox NPs (200 μM) + Ytt Ox NPs (0.5 μg/mL) for 3 days and/or Nan Se (0.01 μM) for 1 day. Then markers of oxidative stress, mitochondrial dysfunction, insulin and glucagon secretion were measured. Results: We reported a decrease in H2O2-induced reactive oxygen species (ROS) level and glucagon secretion, and an increase in H2O2-reduced ATP/ADP ratio, MMP, as well as UCP2 protein expression, and insulin secretion by pretreatment of CRI-D2 cells with Cer and Ytt Ox NPs and/or Nan Se. Conclusion: We found maximum protective effect with Cer and Ytt Ox NPs on CRI-D2 beta-cell line exposed by H2O2 for keeping beta cells alive until transplant whereas combination of Cer and Ytt Ox NPs and Nan Se had very little protective effect in this condition.