Anatoly I. Soloviev*, Maria I. Melnyk, Irina V. Ivanova, Dariia Dryn, and Alexander V. Zholos
Abstract: In excitable cells, potassium channels control not only resting potential, but also cell excitability, and thus underline normal function and various pathological conditions. Therefore, there are continuing efforts towards developing K+ channel openers for the treatment of disease states associated with abnormal cellular activity. The aim of this study was to shed light on the intrinsic mechanisms of Maxi-K (BKCa) channels activation by plasmonic gold nanoparticles (AuNPs) in smooth muscle (SM) cells obtained from different SM tissues. Maxi-K currents in myocytes isolated from rat pulmonary artery and mouse ileum were recorded in the whole-cell and cell-attached configurations of the patch-clamp techniques. We compared the effects of AuNPs on Maxi-K channel activity under weak or strong intracellular Ca2+ buffering (Ca2+ “clamp” at 100 nM). With weak Ca2+ buffering, Maxi-K current density was increased by AuNPs applied at 10-4 M, and further increased by green laser irradiation (GLI, 5 mW, 532 nm). The potentiating effect of AuNPs alone was due to an increase in maximal conductance (Gmax) by about 50% without any shift of the activation curve of K+ conductance. GLI in the presence of AuNPs (AuNPs/GLI) produced little additional effect increasing the maximal K+ conductance, but instead shifted the potential of half-maximal activation (V1/2) value negatively by about 10 mV. Under conditions of strong intracellular Ca2+ buffering, no effect of AuNPs alone or AuNPs/GLI on Maxi-K currents was observed. At the single-channel level, the effects of AuNPs/GLI were due to a significant increase in channel open probability, while single channel conductance remained unchanged. Under these conditions, there was deviation from independence of channel gating, suggesting that plasmon resonance may not similarly affect all channels present in the membrane patch. This type of regulation is fundamentally different from other common types of drug action. We conclude that AuNPs activate Maxi-K channels expressed in different SM tissues via both Gmax increase and a negative V1/2 shift. Moreover, the potentiating effect of AuNPs/GLI is clearly calcium-dependent, as it could be completely abolished by “clamping” the intracellular Ca2+ concentration.
Khanh Thi My Tran, Toi Van Vo, Van-Thanh Tran, Phuong Ha-Lien Tran, and Thao Truong-Dinh Tran*
Abstract: The problem of poor water-solubility has remained as a significant challenge in pharmaceutical industry. The emergence of solid lipid nanoparticles (SLNs) from former colloidal system proposes several advantages namely encapsulation of lipophilic agents, nano-sized particles, absence of organic solvents, and ease of large-scale production. This review aims to provide readers an overview regarding the feasibility and recent applications of SLNs as drug delivery systems for different administrations including oral, skin, ocular, pulmonary and parenteral routes. Researches about SLNs are predicted to continually flourish for an enormous contribution to the fields of medicine.
V. N. Rai* and A. K. Srivastava
This paper presents the study of optical properties and the morphology of the nanostructured gold thin films deposited on the glass substrate. The localized surface plasmon resonance (LSPR) peaks shift to higher wavelength side and reaches up to near infrared region with a controlled increase in the film thickness during its deposition. The shapes and sizes of the nanoparticles change with an increase in the film thickness. The roughness of the films increases, whereas the refractive index of the surrounding medium decreases with an increase in the film thickness. A correlation has been found between the LSPR wavelength, the surface morphology and the refractive index of the surrounding medium of the film. These thin films act as a substrate for surface enhanced spectroscopy and as a sensor for organic and biological samples.
Somesree Ghosh Mitra* and Santaneel Ghosh
The use of novel polymer nanocomposites has attracted considerable interest in the biomedical field. In this article, we review and propose an innovative nanotechnological platform for central nervous system (CNS) drug delivery, based on remotely tunable, multifunctional, and biocompatible polymeric nanostructures. Engineered magnetic nanocarriers with tailored size, volumetric transition range, and magnetic properties based on biocompatible, thermo-responsive oligo(ethylene glycol) methacrylate biopolymers can be designed for sustained and sequential release of growth factors after internalization or surface attachment to the target cells. Precise control of nano-sphere size in the range of 100-300 nm, coupled with a higher and broader volumetric transition range (32-42ºC) is ideal for sustained release of growth factor to the target site. More importantly, super-paramagnetic behavior of the nanocarriers, even after polymer shell shrinkage can generate stable and easily controllable loss mechanisms inside ac magnetic field exposure.
Juan Jose Carreras, Paula Canales and Ana Melero Zaera*
The oral route is the most common and physiological way to administer drugs. Nevertheless, this drug delivery route is always associated to intrinsic difficulties. For instance, some drugs are poorly or non-absorbable in the intestine and cannot access the systemic circulation. On the other side, when the desired effect is topical into the intestinal mucosa, the major disadvantage is the clearance of the drug through absorption to systemic circulation or the excretion due to intestinal motility. Several drug delivery systems have been developed to modify drug absorption, according to the desired activity.
Intestinal mucus is a complex, viscous and elastic layer that can importantly affect drug delivery. The attachment of molecules to the mucus and/or the epithelial surface is therefore worth to investigate. Thereby the resident time of the drug can be increased at the absorption or targeting site. Future strategies are heading into the combination of mucoadhesive and mucopenetrating particles to modify the absorption, and facilitate targeting to the intestinal mucosa.
Thanks to these drug delivery systems, and through several strategies, first pass effect can be avoided, the drug bioavailability can be increased, or targeting to the mucosa can be achieved. In this sense, drugs can be delivered in a very slow release rate, increasing its permanence onto the tissue, producing local effects while reducing the systemic side effects. The nature of the polymer is a key factor to achieve an effective mucoadhesion. Their molecular weight, viscosity, degree of cross-linking, flexibility, concentration and pH have been described as properties affecting this behavior, being the degree of ionization the most important ones. Anionic polymers have showed higher mucoadhesive strength than cationic and non-ionic ones.
In summary, mucoadhesive drug delivery systems are being developed with the aim to provide more effective dosage forms for oral administration. Encapsulation of drugs in different polymers can help retaining the drug on the absorption membrane, which is in this case, also the target tissue, increasing the compliance of the patient.
Small interfering RNAs (siRNAs) therapy has opened exceptional advantageous opportunity for the treatment of diseases. Usually naked siRNA are subjected to internal harsh environment and rapidly degraded by RNases after administration. To overcome this issue various nanodelivery platforms have been developed and utilized in drug delivery due to narrowed size distribution, improved bioavailability and site specific target, impacting lowering of doses. To amenable the delivery of siRNA, various nanovehicles are designed and complexed with specific siRNA for protecting the siRNA payloads and avoiding nonspecific delivery. This review describes the recent developments of siRNA-complexed nanovehicles, which can probably carry forward to the next generation for their successful clinical translation.