Fabrication of Nanostructured Lipid Carriers (NLC)-Based Gels from Microemulsion Template for Delivery Through Skin.

Nanostructured lipid carriers (NLC) represent the novel and widely explored generation of lipid nanoparticles. These are the second-generation solid lipid nanoparticles (SLN) developed with the aim to overcome limitations of SLN mainly with respect to limited drug loading and drug leakage during its storage. NLC are fabricated by mixing solid lipids with spatially incompatible (liquid) lipids leading to nanoparticulate structures with improved drug loading and controllable release properties. Out of the numerous methods reported to prepare NLC, microemulsion template (ME) technique is the most simple and preferred method. This methodology of preparation of lipid nanoparticles obviates the need for specialized equipment and energy to generate NLC, enables achieving desirable particle size of nanoparticles by modulating the size of the emulsion droplet, and is also feasible for easy scale-up. This chapter describes microemulsion template technique for fabrication of NLC based gel for topical delivery, particularly with respect to its method of preparation and product analysis.

Influence of chirality on the thermal and electric properties of the columnar mesophase exhibited by homomeric dipeptides.

We present the first investigation of the influence of chirality on the thermal and electric properties in a biologically important homomeric dipeptide that exhibits a hexagonal columnar liquid crystal mesophase. The peptide employed has two chiral centres, and thus the two possible enantiopures are the (R,R) and (S,S) forms having opposite chirality. The measurements reported the span of the binary phase space between these two enantiopures. Any point in the binary diagram is identified by the enantiomeric excess Xee (the excess content of the R,R enantiopure over its S,S counterpart). We observe that the magnitude of Xee plays a pivotal role in governing the properties as evidenced by X-ray diffraction (XRD), electric polarization (Ps), dielectric relaxation spectroscopy (DRS) measurements, and the isotropic-columnar transition temperature. For example, XRD shows that while other features pointing to a hexagonal columnar phase remain the same, additional short-range ordering, indicating correlated discs within the column, is present for the enantiopures (Xee = ±1) but not for the racemate (Xee = 0). Similarly, an electric-field driven switching whose profile suggests the phase structure to be antiferroelectric is seen over the entire binary space, but the magnitude is dependent on Xee; interestingly the polarization direction is axial, i.e., along the column axis. DRS studies display two dielectric modes over a limited temperature range and one mode (mode 2) connected with the antiferroelectric nature of the columnar structure covering the entire mesophase. The relaxation frequency and the thermal behaviour of mode 2 are strongly influenced by Xee. The most attractive effect of chirality is its influence on the polar order, a measure of which is the magnitude of the axial polarization. This result can be taken to be a direct evidence of the manifestation of molecular recognition and the delicate interplay between chiral perturbations and the magnitude of the polar order, a feature attractive from the viewpoint of devices based on, e.g., remnant polarization-a currently hot topic. To add further dimension to the work, the DRS measurements are also extended to elevated pressures.

Structure-Property Correlations in Cyanobiphenyl-Based Dimer-Like Mesogens.

In this contribution, we present the results of our extensive investigations on the synthesis and phase behavior of five series of dimer-like compounds formed by covalently linking a promesogenic, cyanobiphenyl core, with a nonmesogenic N-(n-alkyl)-salicylaldimine segment via an oxy(oligomethylene)oxy spacer of varying length and parity. This work is a continuation of our previous short study where the occurrence of re-entrant nematic (Nre) phase seemed to be vitally dependent on the parity of the spacer and the length of the terminal chain. Thus, working along these lines the effects on the thermal (Nre phase) behavior of the various spacers and the terminal tails have been investigated comprehensively. In particular, with the aim of exploring the fundamental relationships between molecular structural features and thermal properties, five spacers, namely, oxy(hexyl)oxy, oxy(heptyl)oxy, oxy(octyl)oxy, oxy(nonyl)oxy, and oxy(decyl)oxy spacers, have been used. Each series consists of six mesogens, as the terminal tail attached to the salicylaldimine core has been varied from n-pentyl to n-decyl. For the sake of comparison and completeness, previously reported materials have also been studied in detail, and data are included here. The characterization results derived from the optical and calorimetric studies clearly illustrate a pronounced odd-even effect; however, the effect attenuates as the length of the spacer is elongated. The even-members show higher clearing temperatures and enthalpies of transition than those of adjoining odd-members. Three series of mesogens possessing an even-parity spacer show thermodynamically stable nematic (N) and/or smectic A (SmA) phase(s); the lower homologues display only the N phase, and the middle ones exhibit both N and SmA phases while the higher members show the SmA phase solely. In contrast, the vast majority of the odd-spaced compounds of two series show a monotropic N phase. X-ray diffraction study confirms the partial bilayer order of the SmA (SmAd) phase with L < d < 2L where d is the layer spacing and L is the molecular length. Contrary to what was previously noted, none of the new compounds synthesized favor the stabilization of the Nre phase. At the present time, it is extremely difficult to point out the exact cause for the origin of re-entrant behavior in some compounds exclusively, as they hardly differ in their structure. It was also found that the phase transitional properties of even-members are comparable to that observed for 4'-n-alkoxy-4-cyanobiphenyls (nOCBs) and 4-n-alkyl-4-cyanobiphenyls (nCBs). In essence, our study validates the point that dimer-like compounds resemble liquid crystal (LC) dimers, as well as monomers to some degree, in the context of their thermal behavior; thus, they can be regarded as the bridging structures between LC monomers and dimers.

Polymeric nanoparticles for targeted treatment in oncology: current insights.

Chemotherapy, a major strategy for cancer treatment, lacks the specificity to localize the cancer therapeutics in the tumor site, thereby affecting normal healthy tissues and advocating toxic adverse effects. Nanotechnological intervention has greatly revolutionized the therapy of cancer by surmounting the current limitations in conventional chemotherapy, which include undesirable biodistribution, cancer cell drug resistance, and severe systemic side effects. Nanoparticles (NPs) achieve preferential accumulation in the tumor site by virtue of their passive and ligand-based targeting mechanisms. Polymer-based nanomedicine, an arena that entails the use of polymeric NPs, polymer micelles, dendrimers, polymersomes, polyplexes, polymer-lipid hybrid systems, and polymer-drug/protein conjugates for improvement in efficacy of cancer therapeutics, has been widely explored. The broad scope for chemically modifying the polymer into desired construct makes it a versatile delivery system. Several polymer-based therapeutic NPs have been approved for clinical use. This review provides an insight into the advances in polymer-based targeted nanocarriers with focus on therapeutic aspects in the field of oncology.

Endosomal escape: a bottleneck in intracellular delivery.

With advances in therapeutic science, apart from drugs, newer bioactive moieties like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly being introduced for the betterment of therapeutic efficacy. These moieties have intracellular components of the cells like cytoplasm and nucleus as one of their pharmacological sites for exhibiting therapeutic activity. Despite their promising efficacy, their intracellular bioavailability has been critically hampered leading to failure in the treatment of numerous diseases and disorders. The endosomal uptake pathway is known to be a rate-limiting barrier for such systems. Bioactive molecules get trapped in the endosomal vesicles and degraded in the lysosomal compartment, necessitating the need for effective strategies that facilitate the endosomal escape and enhance the cytosolic bioavailability of bioactives. Microbes like viruses and bacteria have developed their innate mechanistic tactics to translocate their genome and toxins by efficiently penetrating the host cell membrane. Understanding this mechanism and exploring it further for intracellular delivery has opened new avenues to surmount the endosomal barrier. These strategies include membrane fusion, pore formation and proton sponge effects. On the other hand, progress in designing a novel smart polymeric carrier system that triggers endosomal escape by undergoing modulations in the intracellular milieu has further led to an improvement in intracellular delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic cationic lipids and photo-induced physical disruption. Each of the aforementioned strategies has its own unique mechanism to escape the endosome. This review recapitulates the numerous strategies designed to surmount the bottleneck of endosomal escape and thereby achieve successful intracellular uptake of bioactives.

Psoriasis clinical implications and treatment: a review.

Psoriasis is a common skin disorder affecting the population worldwide. It is a T-cell mediated autoimmune disorder leading to keratinocyte hyperproliferation. Psoriasis has genetic predisposition that is further aggravated by certain stimulating factors. In spite of significant advances in understanding the pathogenesis of psoriasis, the exact etiology of the disease remains unknown. The clinical manifestations of this disease include various forms that affect different parts of the body. Treatment options vary according to the mode of application or severity of the disease. Earlier treatments have included application of emollients or keratolytic agents to hydrate the skin or shed off the skin. But later treatments have been modified to treat the underlying T-cell proliferation. Hence, topical treatments like coal tar, vitamin D, retinoids, topical calcineurin inhibitors for treating mild psoriasis, systemic treatments including methotrexate, cyclosporine, acitretin, hydroxyurea, as well as light therapy for severe psoriasis have become more prominent. Current treatment modalities are associated with the risk of serious side effects from prolonged treatment. Combinations of these therapies have provided effective and rapid modalities to suppress the disease and reduce the side effects of treatment. In addition, newer carrier systems for conventional drugs are being developed to improve the effectiveness of treatment and reduce the side effects. Development of biologics and gene therapy have revolutionized the treatment of this skin disease. Although an array of therapies to suppress the psoriatic condition exists, none are curative.

Reentrant nematic phenomenon in a new class of low molar mass, single-component liquid crystals.

We report the observation of reentrant nematic behavior in a relatively new class of compounds, namely, dimerlike mesogens that are made by covalently linking nematogenic cyanobiphenyl and nonmesogenic N-(n-alkyl)salicylaldimine segments through a central flexible spacer of varying length and parity. The existence of reentrant phenomenon in this class of mesogens, evidenced indubitably by means of several complementary studies, appears to be crucially dependent on the length of the terminal alkyl tail and parity of the spacer.