Pharmaceutical Nanotechnology (v.2, #1)

Editorial: by Ijeoma Uchegbu (1-1).

Nanoparticles in the Development of Therapeutic Cancer Vaccines by Ronak Savla, Vera Ivanova, Tamara Minko (2-22).
Cancer vaccines have garnered great interest as a potential arsenal to treat patients with cancer. The main goaland challenge in cancer immunotherapy includes the activation of the otherwise indolent immune system of cancer patients.It has been discovered that cytotoxic T cell mediated immune response is most efficacious in killing cancer cells.However, even if the immune system of a cancer patient is activated, there is no guarantee that such activation will betranslated into cancer cell death. Nanotechnology has already transformed the field of small molecule therapy and holdspromise to have similar impact on the field of cancer vaccines. Nanoparticles can be tailored to target specific receptors inimmune competent or cancer cells and even elicit specific type of immune response. Desirable effects of nanoparticles canbe controlled through modification of factors such shape, size, surface charge, composition, and hydrophobicity. Anotheradvantage of nanoparticles includes the ability of simultaneous delivery of multiple antigens and adjuvant-antigen combinations,thereby increasing the likelihood of triggering an immune response. Extrapolating from the progress that nanoparticleshave helped to make in other areas, it can be anticipated that nanotechnology approach would accelerate the processof clinical applications of cancer vaccines.

The Multifaceted Potential of Electro-spinning in Regenerative Medicine by Kieran Fuller, Abhay Pandit, Dimitrios I. Zeugolis (23-34).
The increased interest in nanotechnology has resulted in an intense investigation and development of nanofabricationmethods. Among the bottom-up approaches, electro-spinning has attracted great interest in recent years. Thepopularity of electro-spinning lays on the fact that it is a relatively simple and economic technique that enables productionof large quantities of nano- to micro-meter range fibrous materials with various morphologies and architectural features.The versatility of electro-spinning is evidenced by the range of applications being utilised, including filtration, textiles,batteries, and tissue engineering and regenerative medicine. Specifically to biomedical applications, advancements in theelectro-spinning setup have allowed the development of electro-spun mats that closely imitate native extracellular matrixassemblies and provide opportunities for localised and sustained delivery of therapeutics. Herein, we are discussing differentelectro-spinning setups and their distinct benefits for regenerative medicine applications.

The present study reports the transfection and cytotoxicity of hyperbranched poly (2-dimethylaminoethylmethacrylate)(pDMAEMA) based polymer at various physiological conditions. Transfection capability andcytotoxicity of the hyperbranched polymer were first evaluated by varying the molecular weight upon PEGylation. Hyperbranchedpolymer with optimal PEGylation was later protonized and the effect of protonation was evaluated. Finally,the effects of serum on transfection and cellular metabolic activity on various cell types were investigated. Results suggestthat hyperbranched polymer with medium PEGylation (Mw 24000Da) and protonation were best suited for transfectionwhich exhibited minimal toxicity. However, the effect of serum was cell-type dependent.

Cellular Response to Ferroelectric PVDF-TrFE Nanoscale Surfaces Formed by Varying Polymer Concentration by Manus J.P. Biggs, Eva Parisi Capdevila, Catalina Valejo-Giraldo, Shalom J. Wind (42-48).
Poly[(vinylidenefluoride-co-trifluoroethylene] [PVDF(TrFE)], a ferroelectric polymer capable of undergoingstrain of up to 7% is both highly chemically resistant and has the advantage of being cytocompatible. Here we present apreliminary study into the response of mesenchymal stem cells to spin-coated PVDF(TrFE) films and examine how thepolymer concentration influences electrophysical film properties and cell adhesion. Surface characterization was quantitativelyassayed in terms of topography, roughness, wettability and chemistry, while the ferroelectric response of the filmswas confirmed via electrical probing of the polarization-field hysteresis. At the micron- and nanoscale scale, AFM analysisrevealed that PVDF(TrFE) exhibited increased roughness and topographical features with increasing PVDF(TrFE)concentration. PVDF(TrFE) films displayed higher contact angles compared with control glass substrates, as indicated bywettability assay, yet elemental composition was unchanged. Electric field/polarization response analysis revealed filmsrequired bias voltages of up 100 v to undergo saturated polarisation hysteresis. Mesenchymal stem cells were cultured onPVDF(TrFE) films for up to 7 days, and assessed by morphometric analysis, focal adhesion quantification and real-timePCR. Cells grown on films formed from 3% w/v PVDF(TrFE) solutions exhibited significantly higher expression of FAKand focal adhesion reinforcement following 1 day of culture, indicating nanoscale roughness in PVDF(TrFE) films as apotent modulator of MSC adhesion to ferroelectric polymers.

Scope: P-glycoprotein (P-gp) is found to play a very significant role in intestinal transport of losartan, an antihypertensivedrug with variable and low oral bioavailability (33%), is a substrate for both CYP 3A4 and P-gp. This makesP-gp inhibition a logical strategy for improving losartan's oral efficacy and reducing its toxicity. Thus, we investigatedwhether the co-administration of piperine, quercetin, and polysorbate 80 could increase losartan's pharmacokinetic activity invivo. Methods and results: We determined the effect of piperine, quercetin, and polysorbate 80 coadministered with losartanon plasma levels in rats by HPLC assay. Rats were administered losartan (10mg/kg; oral gavage) or losartan (10mg/kg;oral gavage) +piperine (10mg/kg; oral gavage) or losartan (10mg/kg; oral gavage) +quercetin (7.5mg/kg; oral gavage) orlosartan (10mg/kg; oral gavage) +polysorbate 80 (1%w/v of drug solution; oral gavage), and the plasma levels of losartanwere analyzed at different time intervals. Inhibition of p-gp activity resulted in an increased area under the curve (AUC),maximum plasma concentration (Cmax), and mean residence time (MRT) of losartan when compared to losartan alone.Conclusions: Losartan is one of the most widely used antihypertensive agents. Dietary constituents and pharmaceuticalexcipients are important agents modifying drug transport. In our studies, consumption of piperine, quercetin, and polysorbate80 increases the therapeutic efficacy of losartan without inducing adverse effects on the treated mice.