Lipid-based microemulsion gel for the topical delivery of methotrexate: an optimized, rheologically acceptable formulation with conducive dermatokinetics.

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.

Promises of Lipid-Based Nanocarriers for Delivery of Dimethyl Fumarate to Multiple Sclerosis Brain.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the central nervous system (CNS) infecting 2.5 million people worldwide. It is the most common nontraumatic neurological impairment in young adults. The blood-brain barrier rupture for multiple sclerosis pathogenesis has two effects: first, during the onset of the immunological attack, and second, for the CNS self-sustained "inside-out" demyelination and neurodegeneration processes. In addition to genetic variations, environmental and lifestyle variables can also significantly increase the risk of developing MS. Dimethyl fumarate (DMF) and sphingosine-1-phosphate (S1P) receptor modulators that may pass the blood-brain barrier and have positive direct effects in the CNS with quite diverse mechanisms of action raise the possibility that a combination therapy could be successful in treating MS. Lipid nanocarriers are recognized as one of the best drug delivery techniques to the brain for effective brain delivery. Numerous scientific studies have shown that lipid nanoparticles can enhance the lipid solubility, oral bioavailability, and brain availability of the drugs. Nanolipidic carriers for DMF delivery could be derived through vitamin D, tocopherol acetate, stearic acid, quercetin, cell-mimicking platelet-based, and chitosan-alginate core-shell-corona-shaped nanoparticles. Clinical and laboratory diagnosis of MS can be performed mainly through magnetic resonance imaging. The advancements in nanotechnology have enabled the clinicians to cross the blood-brain barrier and to target the brain and central nervous system of the patient with multiple sclerosis.

Emerging Advances in Nanocarriers Approaches in the Effective Therapy of Pain Related Disorders: Recent Evidence and Futuristic Needs.

Pain disorders are the primary cause of disability nowadays. These disorders, such as rheumatoid arthritis (RA) and osteoarthritis (OA), cause loss of function, joint pain and inflammation and deteriorate the quality of life. The treatment of these inflammatory diseases includes anti-inflammatory drugs administered via intra-articular, topical or oral routes, physical rehabilitation or surgery. Owing to the various side effects these drugs could offer, the novel approaches and nanomaterials have shown potential to manage inflammatory diseases, prolonged half-life of anti-inflammatory drugs, reduced systemic toxicity, provide specific targeting, and refined their bioavailability. This review discusses in brief about the pain pathophysiology and its types. The review summarizes the conventional therapies used to treat pain disorders and the need for novel strategies to overcome the adverse effects of conventional therapies. The review describes the recent advancements in nanotherapeutics for inflammatory diseases using several lipids, polymers and other materials and their excellent efficiency in improving the treatment over conventional therapies. The results of the nanotherapeutic studies inferred that the necessity to use nanocarriers is due to their controlled release, targeting drug delivery to inflamed tissues, low toxicity and biocompatibility. Therefore, it is possible to assert that nanotechnology will emerge as a great tool for advancing the treatment of pain disorders in the near future.

Proliposome-Based Nanostrategies: Challenges and Development as Drug Delivery Systems.

Many attempts have been made to the refinement of liposomal stability. In 1986, Payne et al. developed the approach of proliposomes to derelict the physicochemical instability confronted in some liposome suspensions, i.e., fusion, aggregation, hydrolysis, and oxidation. This review attempts to cover different aspects of proliposomes along with their types and preparation methods. The review is also focused on the scope of proliposomes as a nano-based drug delivery system and subsequent applications. An attempt has been made to cover all the facets of proliposomes, from their composition to clinical trials. The extensive scientific data from proliposomes provide substantial shreds of evidence for its huge delivery potential.

Oral sorafenib-loaded microemulsion for breast cancer: evidences from the in-vitro evaluations and pharmacokinetic studies.

Sorafenib tosylate (SFB) is a multikinase inhibitor that inhibits tumour growth and proliferation for the management of breast cancer but is also associated with issues like toxicity and drug resistance. Also, being a biopharmaceutical class II (BCS II) drug, its oral bioavailability is the other challenge. Henceforth, this report intended to encapsulate SFB into a biocompatible carrier with biodegradable components, i.e., phospholipid. The microemulsion of the SFB was prepared and characterized for the surface charge, morphology, micromeritics and drug release studies. The cell viability assay was performed on 4T1 cell lines and inferred that the IC50 value of sorafenib-loaded microemulsion (SFB-loaded ME) was enhanced compared to the naïve SFB at the concentrations of about 0.75 µM. More drug was available for the pharmacological response, as the protein binding was notably decreased, and the drug from the developed carriers was released in a controlled manner. Furthermore, the pharmacokinetic studies established that the developed nanocarrier was suitable for the oral administration of a drug by substantially enhancing the bioavailability of the drug to that of the free SFB. The results bring forth the preliminary evidence for the future scope of SFB as a successful therapeutic entity in its nano-form for effective and safer cancer chemotherapy via the oral route.

Lipid-based Nanocarriers Loaded with Taxanes for the Management of Breast Cancer: Promises and Challenges.

Breast cancer is the leading cause of deaths worldwide among women. Taxanes (most propitious class of diterpenes) have shown dynamic potentials in the treatment of early and metastatic breast cancer. However, challenges like poor bioavailability, low tissue-permeability, compromised aqueous solubility, and dose-dependent side-effects limit the clinical applications of these drugs. Henceforth, to overcome these challenges, various nanotechnology-based drug delivery systems are being explored for the delivery of taxanes in the management of breast cancer. One such promising nanocarrier category is lipid-based nanocarriers, which employ the meritorious features of a variety of lipids, both of natural and synthetic origin. It is also known that lipid uptake plays a significant role in breast cancer cells proliferation and tumor genesis. However, lipid-based nanocarriers could be a great choice to nanoencapsulate the poorly soluble and permeable taxanes for breast cancer management. These systems have an immense promise of bioavailability enhancement, spatial and temporal taxane delivery, improved efficacy, reduced dosing frequency, and even mild inhibition of the P-gp efflux mechanism. Apart from these promises, these carriers are not yet available for the benefit of the end-user. The present review will not only discuss the merits, progress, and promises of these systems but also ponder upon the various challenges faced by these carriers to reach the clinics for the benefit of the patients afflicted with breast cancer.