Morphologic design of nanostructures for enhanced antimicrobial activity

Despite significant progress in synthetic polymer chemistry and in control over tuning the structures and morphologies of nanoparticles, studies on morphologic design of nanomaterials for the purpose of optimizing antimicrobial activity have yielded mixed results. When designing antimicrobial materials, it is important to consider two distinctly different modes and mechanisms of activity-those that involve direct interactions with bacterial cells, and those that promote the entry of nanomaterials into infected host cells to gain access to intracellular pathogens. Antibacterial activity of nanoparticles may involve direct interactions with organisms and/or release of antibacterial cargo, and these activities depend on attractive interactions and contact areas between particles and bacterial or host cell surfaces, local curvature and dynamics of the particles, all of which are functions of nanoparticle shape. Bacteria may exist as spheres, rods, helices, or even in uncommon shapes (e.g., box- and star-shaped) and, furthermore, may transform into other morphologies along their lifespan. For bacteria that invade host cells, multivalent interactions are involved and are dependent upon bacterial size and shape. Therefore, mimicking bacterial shapes has been hypothesized to impact intracellular delivery of antimicrobial nanostructures. Indeed, designing complementarities between the shapes of microorganisms with nanoparticle platforms that are designed for antimicrobial delivery offers interesting new perspectives toward future nanomedicines. Some studies have reported improved antimicrobial activities with spherical shapes compared to non-spherical constructs, whereas other studies have reported higher activity for non-spherical structures (e.g., rod, discoid, cylinder, etc.). The shapes of nano- and microparticles have also been shown to impact their rates and extents of uptake by mammalian cells (macrophages, epithelial cells, and others). However, in most of these studies, nanoparticle morphology was not intentionally designed to mimic specific bacterial shape. Herein, the morphologic designs of nanoparticles that possess antimicrobial activities per se and those designed to deliver antimicrobial agent cargoes are reviewed. Furthermore, hypotheses beyond shape dependence and additional factors that help to explain apparent discrepancies among studies are highlighted

Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure

Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions

Brain-targeted delivery of Valsartan using solid lipid nanoparticles labeled with Rhodamine B; a promising technique for mitigating the negative effects of stroke

AbstractThe brain is a vital organ that is protected from the general circulation and is distinguished by the presence of a relatively impermeable blood brain barrier (BBB). Blood brain barrier prevents the entry of foreign molecules. The current research aims to transport valsartan (Val) across BBB utilizing solid lipid nanoparticles (SLNs) approach to mitigate the adverse effects of stroke. Using a 32-factorial design, we could investigate and optimize the effect of several variables in order to improve brain permeability of valsartan in a target-specific and sustained-release manner, which led to alleviation of ischemia-induced brain damage. The impact of each of the following independent variables was investigated: lipid concentration (% w/v), surfactant concentration (% w/v), and homogenization speed (RPM) on particle size, zeta potential (ZP), entrapment efficiency (EE) %, and cumulative drug release percentage (CDR) %. TEM images revealed a spherical form of the optimized nanoparticles, with particle size (215.76 ± 7.63 nm), PDI (0.311 ± 0.02), ZP (-15.26 ± 0.58 mV), EE (59.45 ± 0.88%), and CDR (87.59 ± 1.67%) for 72 hours. SLNs formulations showed sustained drug release, which could effectively reduce the dose frequency and improve patient compliance. DSC and X-ray emphasize that Val was encapsulated in the amorphous form. The in-vivo results revealed that the optimized formula successfully delivered Val to the brain through intranasal rout as compared to a pure Val solution and evidenced by the photon imaging and florescence intensity quantification. In a conclusion, the optimized SLN formula (F9) could be a promising therapy for delivering Val to brain, alleviating the negative consequences associated with stroke

Development of Sedative Dexmedetomidine Sublingual In Situ Gels: In Vitro and In Vivo Evaluations

Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX sublingual in situ gels were developed and assessed for their pH, gelling capacity, viscosity, mucoadhesion and in vitro drug release. The optimized gelling system demonstrated enhanced mucoadhesion, superior gelling capacity, reasonable pH and optimal rheological profile. In vivo, compared to the oral solution, the optimal sublingual gel resulted in a significant higher rate and extent of bioavailability. Although the in situ gel had comparable plasma levels to those observed following intravenous administration, significant amelioration of the systemic adverse reactions were attained. As demonstrated by the hot plate method, a sustained duration of analgesia in rats was observed after sublingual administration of DEX gel compared to the intravenously administered DEX solution. Furthermore, no changes in systolic blood pressure and heart rate were recorded in rats and rabbits, respectively, after sublingual administration of DEX. Sublingual administration of DEX in situ gel provides a promising approach for analgesia and sedation, while circumventing the reported adverse reactions associated with intravenous administration of DEX