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.

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.