Abstract
The pH-sensitive liposomes have been extensively used as an alternative to conventional liposomes in effective intracellular delivery of therapeutics/antigen/DNA/diagnostics to various ...compartments of the target cell. Such liposomes are destabilized under acidic conditions of the endocytotic pathway as they usually contain pH-sensitive lipid components. Therefore, the encapsulated content is delivered into the intracellular bio-environment through destabilization or its fusion with the endosomal membrane. The therapeutic efficacy of pH-sensitive liposomes enables them as biomaterial with commercial utility especially in cancer treatment. In addition, targeting ligands including antibodies can be anchored on the surface of pH-sensitive liposomes to target specific cell surface receptors/antigen present on tumor cells. These vesicles have also been widely explored for antigen delivery and serve as immunological adjuvant to enhance the immune response to antigens. The present review deals with recent research updates on application of pH-sensitive liposomes in chemotherapy/diagnostics/antigen/gene delivery etc.
Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a ...special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin.
Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier.
In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it.
The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene.
Nanotheranostics, an approach of combining both diagnosis and therapy, is one of the latest advances in cancer therapy particularly. Nanocarriers designed and derived from inorganic materials such as ...like gold nanoparticles, silica nanoparticles, magnetic nanoparticles and carbon nanotubes have been explored for tremendous applications in this area. Similarly, nanoparticles composed of some organic material alone or in combination with inorganic nano-cargos have been developed pre-clinically and possess excellent features desired. Photothermal therapy, MRI, simultaneous imaging and delivery, and combination chemotherapy with a diagnosis are a few of the known methods exploring cancer therapy and detection at organ/tissue/molecular/sub-cellular level. This review comprises an overview of the recent reports meant for nano theranostics purposes. Targeted cancer nanotheranostics have been included for understating tumor micro-environment or cell-specific targeting approach employed. A brief account of various strategies is also included for the readers highlighting the mechanism of cancer therapy.
Nanopharmaceuticals serve as emerging forms of modern medicines, which include nanomedicines, nanosimilars, nanotheranostics, nanodevices, and many more. In the last two decades, a large number of ...nano-based products have reached the market and are being used clinically.
Unlike conventional pharmaceutical products, nanopharmaceuticals behave differently both in vitro and in vivo, and therefore, the development of their generic versions needs special attention to replicate the similar drug release pattern leading to an identical therapeutic outcome. Further, drug-device combinations and 3D products are the latest advancements in precision medicine delivery and development.
The regulatory guidelines for these products are being framed at many stages by various regulatory agencies like USFDA/EMA and still are in infancy at the moment if we look at wider perspectives and applications of nanomedicine.
For a formulation scientist, it is much needed that well-explained and directive guidelines should be made available before leading to the development of the generic versions of these nano-cargos.
Here, in this review, we have summarized the silent features of the regulatory perspectives related to nanotechnology based next generation therapeutics and diagnostics.
Controlled delivery of a bioactive to specific organ, cellular and sub-cellular level is a desired feature of a drug carrier system. In order to achieve this goal, formulation scientists search for ...better alternatives of biomaterials to deliver the therapeutics in more precise and controlled manner in vivo. Zein, a plant protein obtained from corn, is a useful biomaterial for several industrial applications including agriculture, cosmetics, packaging and pharmaceuticals. Being a hydrophobic protein, which is biodegradable, biocompatible, economic to use and with generally regarded safe "GRAS" status, it is an attractive biomaterial for human use. Novel biomedical applications of zein such as controlled and targeted delivery of bioactives and tissue engineering are the current research interests of the scientific fraternity. Here we attempt to review the literature on zein as a biopolymer for drug/vaccine/gene delivery and its applicability in tissue engineering.
Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and ...its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.
Abstract Solid lipid nanoparticles (SLNs) are essentially composed of triglyceride(s) that orient to form a polar core with polar heads oriented toward the aqueous phase, resembling chylomicrons. The ...composition of such SLNs may alter the course of drug absorption predominantly to and through lymphatic route and regions, presumably following a transcellular path of lipid absorption, especially by enterocytes and polar epithelial cells of the intestine. SLNs were prepared using stearic acid, glycerol monostearate, tristearin, and Compritol 888 ATO by solvent diffusion method using demineralized double-distilled water as the dispersion medium. The SLNs were characterized for shape, size, zeta potential, and percentage drug content and its release. The characterization of SLNs suggests that Compritol 888 ATO–based nanoparticles were heterogeneous with better drug-loading and release characteristics as compared with the other formulations. The selected products were studied for in vivo absorption and hence bioavailability by measure of area under the blood plasma curve plotted as a function of time. Periodic lymphatic concentration of drug following oral administration of respective formulations was also determined by mesenteric duct cannulation and collection of samples. The comparative study conducted on methotrexate (MTX)-bearing SLNs revealed that the formulation based on Compritol 888 ATO could noticeably improve the oral bioavailability of MTX, presumably following SLNs constituting lipid digestion and co-absorption through lymphatic transport and route.
Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous ...treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.
The aim of the present study was to develop chylomicron mimicking carrier emulsome for oral lymphatic delivery of methotrexate (MTX), an anticancer drug. The compritol 888 ATO (CA) was used as lipid ...core and soya lecithin (PC) as stabilizer. The optimized emulsome (1:1.2 mole ratio of CA:PC) showed mean particle size of 160.3
±
10.2
nm and with 72.8
±
6.5% drug entrapment efficiency. The differential scanning calorimetric studies revealed a depression in endothermic onset for MTX loaded emulsome. The rapid burst release of the drug was observed in simulated gastric fluid (SGF pH 1.2) with significant increase in particle size of emulsome. However in simulated intestinal fluid (SIF, pH 7.4) a slow and consistent release of the drug was obtained over period of 24
h. Storage stability studies were performed at different temperatures (4
±
1 and 25
±
1
°C) for 3 months which suggested that EML remain more stable when stored at refrigerated condition. The
in vivo studies were carried out on albino rats and response was estimated collecting blood and lymph both. The pharmacokinetic parameters
C
max,
t
max and AUC
0→12
h
after duodenal administration of optimized emulsomal formulation and plain MTX solution were 7.1 and 2.4
μg/mL, 4 and 1
h, 40.45 and 7.2
h
μg/mL respectively. The relative bioavailability of MTX was enhanced nearly 5.7 times with optimized EML formulation when compared to plain MTX solution with higher uptake and longer residence time of MTX molecules in lymphatics. Thus, emulsome could be used as lymphotropic carrier for delivery of bioactive(s) and hence for bioavailability enhancement.
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