Intranasal delivery of antipsychotic drugs.

Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery.

Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation.

Inhibitors of microsomal prostaglandin E2 synthase-1 enzyme as emerging anti-inflammatory candidates.

Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid (AA) into PGH2 that is further metabolized by terminal prostaglandin (PG) synthases into biologically active PGs, for example, prostaglandin E2 (PGE2), prostacyclin I2 (PGI2), thromboxane A2 (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 alpha (PGF2α). Among them, PGE2 is a widely distributed PG in the human body, and an important mediator of inflammatory processes. The successful modulation of this PG provides a beneficial strategy for the potential anti-inflammatory therapy.

The effect of elevated steroids released by reproductive male round gobies, Neogobius melanostomus, on olfactory responses in females.

The round goby, Neogobius melanostomus, is a highly successful invasive species in the Laurentian Great Lakes. Previous behavioral studies implied that females are attracted by pheromones to the nests of reproductive males, and that males release putative steroidal pheromones--unconjugated as well as conjugated forms of 3α-hydroxy-5β-androstane-11,17-dione (11-O-ETIO)-following stimulation of the hypothalamic--gonadal axis with salmon gonadotropin releasing hormone analog (sGnRHa). In this study, we tested the olfactory system of females in response to extracts containing these released steroids.

Release of free and conjugated forms of the putative pheromonal steroid 11-oxo-etiocholanolone by reproductively mature male round goby (Neogobius melanostomus Pallas, 1814).

Previous studies of the round goby (Neogobius melanostomus Pallas, 1814), an invasive fish species in the Laurentian Great Lakes of North America, have shown that this species has the ability to both synthesize and smell steroids that have a 5 beta-reduced and 3 alpha-hydroxyl (5 beta,3 alpha) configuration. An enzyme-linked immunoassay (EIA) for 3 alpha-hydroxy-5 beta-androstane-11,17-dione (11-O-ETIO) has been used to show a substantial rise in the rate of release of immunoreactive compounds into the water when males are injected with salmon gonadotropin releasing hormone analogue. Similar increases were noted for 11-ketotestosterone and 17,20 beta-dihydroxypregn-4-en-3-one.

Memory antibody response from antigen loaded polymer particles and the effect of antigen release kinetics.

Memory antibody response is the hallmark of long lasting immunity. In this study, we report the generation of memory antibody response while immunizing with single dose of polymer particle entrapped antigens. Immunization with admixture of alum and polylactide (PLA) polymer particles (2-8 microm) entrapping antigens not only elicited long lasting primary antibody response but also very high levels of memory antibody titer upon re-exposure to very small amount of soluble antigen.

Role of alum in improving the immunogenicity of biodegradable polymer particle entrapped antigens.

This study was aimed at understanding the role of alum in improving the immunogenicity of biodegradable polymer particle entrapped antigens. Presence of alum formed a fine network around PLA particles holding them together and promoted attachment of higher number of particles on macrophage surface for a considerable period of time. Use of alum lowered the burst release of the entrapped antigen from particles and thereafter also reduced the cumulative release of antigen from particles.

Making polymeric micro- and nanoparticles of complex shapes.

Polymeric micro- and nanoparticles play a central role in varied applications such as drug delivery, medical imaging, and advanced materials, as well as in fundamental studies in fields such as microfluidics and nanotechnology. Functional behavior of polymeric particles in these fields is strongly influenced by their shape. However, the availability of precisely shaped polymeric particles has been a major bottleneck in understanding and capitalizing on the role of shape in particle function.

Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers.

Encapsulation of therapeutic agents in polymer particles has been successfully used in the development of new drug carriers. A number of design parameters that govern the functional behavior of carriers, including the choice of polymer, particle size and surface chemistry, have been tuned to optimize their performance in vivo. However, particle shape, which may also have a strong impact on carrier performance, has not been thoroughly investigated.

Influences of excipients on in vitro release and in vivo performance of tetanus toxoid loaded polymer particles.

Protein instability during microencapsulation has been one of the major hurdles of biodegradable polymer particles-based vaccine delivery systems. In the present work, effect of serum albumin, sucrose and sodium bicarbonate on surface morphology, entrapment efficiency, in vitro release and in vivo performance tetanus toxoid (TT) loaded PLA particles were investigated. Use of serum albumin as well as high concentration of protein antigen ( approximately 60mg/ml) helped in protecting the immunoreactivity of the antigen during primary emulsification step of particle formulation.

Immunogenicity and lower dose requirement of polymer entrapped tetanus toxoid co-administered with alum.

Low adjuvanticity of microparticles based vaccine formulation necessitates the use of alum along with particles to elicit improved antibody titers from single point immunization. It was observed that antibody response from immunization with admixture of alum and polymer entrapped antigen was dependent on particle size, amount of antigen released during burst phase and dose of microencapsulated antigen. In the animals immunized with polymer entrapped tetanus toxoid (TT) very large particles (50-150 microm) did not elicited high antibody titers where as microparticles in the range 2-8 microm exhibited remarkable improvement in the antibody response.

Influence of particle size, antigen load, dose and additional adjuvant on the immune response from antigen loaded PLA microparticles.

Polylactide (PLA) polymer particles entrapping tetanus toxoid (TT) were evaluated in terms of particle size, antigen load, dose and additional adjuvant for achieving high and sustained anti-TT antibody titer from single point intramuscular immunization. Admixture of polymer entrapped TT and alum improved the immune response in comparison to particle-based immunization. High and long lasting antibody titer was achieved upon immunization with 2-8 microm size particles.

Improved immune response from biodegradable polymer particles entrapping tetanus toxoid by use of different immunization protocol and adjuvants.

Poly lactide-co-glycolide (PLGA) and polylactide (PLA) particles entrapping immunoreactive tetanus toxoid (TT) were prepared using the solvent evaporation method. The effect of different formulation parameters such as polymer hydrophobicity, particle size and use of additional adjuvants on the generation of immune responses in experimental animals was evaluated. Immune responses from hydrophobic polymer particles were better than those from hydrophilic polymer.