Pharmaceutical Nanotechnology - Volume 6, Issue 1, 2018
Volume 6, Issue 1, 2018
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Cytotoxicity of Nanomaterials: Using Nanotoxicology to Address the Safety Concerns of Nanoparticles
Authors: Mohd A. Saifi, Wahid Khan and Chandraiah GoduguBackground: The rapid progress in the application of different types of nanoparticles in various biomedical applications resulted in substantial increase in the use of these materials. The special physicochemical properties like small size and increased surface area offered by nanoparticles may pose unexpected toxicologic threats despite of offering promising biological effects. Objective: The intended as well as unintended exposure of nanoparticles to humans is a major challenge for the expanding field of nanoparticle therapy. In this review, an attempt has been made to briefly discuss the different factors affecting nanoparticle mediated toxicity, mechanism of toxicity, and interference of NPs with bioassays. A comprehensive overview has been provided for the in vitro and in vivo toxicologic assessment of NPs and what and how framing guidelines should be used for global unification of nanotoxicologic studies. Conclusion: The present review entails a discussion of the toxicity of nanoparticles along with interferences inherent to nanoparticles in toxicity studies. The lack of availability of regulatory guidelines for nanoparticles is one of the biggest issues. Our understanding of the mechanisms of NP-induced toxicity is superficial; thus, it is too early to come to a general consensus on the toxicity of NPs. There is a need, therefore, to standardize and validate the toxicity testing assays based on NPs properties.
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Nano-Medicine as a Newly Emerging Approach to Combat Human Immunodeficiency Virus (HIV)
Background: Human Immuno deficiency Virus (HIV) infection has attained pandemic level due to its complexity on both the HIV infection cycle and on the targets for drug delivery. This limits medication and consequently requires prominent and promising drug delivery systems to be invented. Notably, various nanomaterial have been studied to enhance effective delivery of the antiretroviral drugs for HIV prevention, diagnosis and cure. Some of these nanomaterials are liposomes, dendrimers, inorganic nanoparticles (NPs), polymeric micelles, natural and synthetic polymers. Objective: The present study aimed to review the recent progress in nanomedicine as a newly emerging approach to combat HIV. Method: The scientific data bases reviewed carefully to find both in vitro and in vivo studies representing the role of nonomedicine to combat HIV. Result: Impressively, nanomedicine drug delivery systems have been commendable in various models ranging from in vitro to in vivo. It gives notion about the application of nano-carrier systems for the delivery of anti-retroviral drugs which ideally should provide better distribution to surpass Blood- Brain Barrier (BBB) and other tissue or to overcome innate barriers such as mucus. Considerably, nanomaterials such as dendrimers and many other inorganic NPs such as silver, gold, iron, and zinc can be used for HIV treatment by interfering in varying stages of HIV life cycle. Furthermore, NPs could best act as adjuvants, convoys during vaccine delivery, as intra-vaginal microbicides and for the early detection of HIV-1 p24 antigen. Conclusion: Nanomedicine may be a proper approach in HIV/AIDS therapy by means of offering lower dosage and side effect, better patient-to-patient consistency, bioavailability, target specificity and improved sensitivity of HIV diagnosis.
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Biocompatible Synthetic and Semi-synthetic Polymers - A Patent Analysis
Authors: Balu Ranganathan, Charles Miller and Anthony SinskeyBackground: Bioengineering has come of ages by setting up spare parts manufacturing units to be used in human body such as invasive implants and interventional controlled drug delivery in vivo systems. As a matter of fact patients on basis of their fiscal strength have the option to undergo prophylactic tactical manoeuvre for longer life spans. In this sphere of invasive implants, biocompatible polymer implants are a state of the art cutting edge technology with outstanding innovations leading to number of very successful start-up companies with a plethora of patent portfolios. Objective: From 2000 onwards, patent filings and grants for biocompatible polymers are expanding. Currently definition of biocompatibility is quite ambiguous with respect to the use of FDA approved polymeric materials. This article analysed patent portfolios for the trend patterns of prolific biocompatible polymers for capitalization and commercialization in the forthcoming years. Method: Pair Bulk Data (PBD) portal was used to mine patent portfolios. In this patent preliminary analysis report, patents from 2000 to 2015 were evaluated using 317(c) filings, grants and classifications data for poly(vinyl alcohol) (PVA), poly(glycolic acid) (PGA), poly(hydroxyalkanoates) (PHAs) and poly(lactic acid) (PLA). Conclusion: This patent portfolio preliminary analysis embarks into patent analysis for New Product Development (NPD) for corporate R investment managerial decisions and on government advocacy for federal funding which is decisive for developmental advances. An in-depth patent portfolio investigation with return of investment (RoI) is in the pipeline.
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Topical Delivery of Erythromycin Through Cubosomes for Acne
Authors: Sana Khan, Poorva Jain, Sourabh Jain, Richa Jain, Saurabh Bhargava and Aakanchha JainBackground: Topical delivery is an attractive route for local and systemic treatment. The novel topical application has many advantages like averting the GI-irritation, preventing the metabolism of drugs in the liver and increasing the bioavailability of the drug over the conventional dosage forms. Objective: The aim of present work was to prepare and characterized erythromycin encapsulated cubosomes using different concentrations of glyceryl monooleate and poloxamer 407 by the emulsification method. Methods: The prepared dispersion of cubosomes was characterized for surface morphology, particle size, entrapment efficiency and in vitro release. Further, optimized formulation was converted to cubosomal gel by incorporating carbopol 934 at different concentrations. The prepared gel was characterized for homogeneity, pH, viscosity, spreadibility, drug content and in vitro drug release study. Results: The result of optimized cubosomes showed average particle size of 264.5±2.84nm and entrapment efficiency about 95.29±1.32 % and the pH of optimized cubosomal was found to be 6.5, viscosity 2475-8901(cp), drug content 95.29% and the spreadability was found to be 11.74 gm.cm/sec. The in vitro drug release kinetics of optimized formulation was found to follow Korsmeyer peppas model having highest R2 value 0.835 and in vitro drug release of optimized erythromycin loaded cubosomal gel and plain drug gel in 24 hr was found to be 89.91±0.73 and 88.64±2.16, while in 36 hr plain drug gel and cubosomal gel showed drug release about 87.64±0.97 and 91.55±1.09, and sustained release was obtained after 24 hr in case of cubosomal gel. Conclusion: Thus, as a whole it can be concluded that erythromycin loaded cubosomes are effective in topically delivering drug in sustained and non-invasive manner for treatment and prevention of acne.
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Tangential Flow Filtration Technique: An Overview on Nanomedicine Applications
Purification is a key step for different types of approaches, ranging from food, biotechnology to pharmaceutical fields. In biotechnology, tangential flow filtration (TFF) allows obtaining the separation of different components of cells without instability phenomena. In the food industry, TFF ensures the removal of contaminants or other substances that negatively affect visual appearance, organoleptic attributes, nutritional value and/or safety of ailments. In the pharmaceutical area, purification is also an important and necessary step controlling the quality of final product. In the field of research and development of nanomedicines, several techniques are used to purify and/or to concentrate the batches for in vitro and in vivo applications. Despite many approaches that exist; current data reveal continued unsatisfactory results. Between them, TFF showed promising results, even if, currently, its use is uncommon if compared with other purification techniques usually reported in “materials and methods” sections. This review represents an overview of the different applications of TFF from protein purification to food application, with particular attention to the field of nanomedicine from polymeric to metallic nanoparticles, highlighting advantages and dis-advantages in the use of this technique. The theoretical aspect of the process has been examined.
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Extracellular Synthesis of Selenium Nanoparticles from an Actinomycetes Streptomyces griseoruber and Evaluation of its Cytotoxicity on HT-29 Cell Line
Authors: V.R. Ranjitha and V.R. RavishankarBackground: Selenium nanoparticles (SeNPs) have gained significant importance because of its bioavailability, least toxicity, its interaction with proteins and its biocompatibility. Objective: In the present study, the extracellular synthesis of SeNPs was carried out by using culture supernatant of Streptomyces griseoruber, an Actinomycetes member isolated from the soil and cytotoxicity was tested on HT-29 cell line. Method: Culture supernatant was mixed with 1mM sodium selenite for the biosynthesis of SeNPs. Characterisation of the synthesised SeNPs was done by UV-Visible spectrophotometer, FTIR, XRD, DLS and HR-TEM. The cytotoxicity of nanoparticles on HT-29 cell line was studied by MTT assay and with different staining procedure. Result: Bioreduction of SeNPs was confirmed by UV-Visible spectrophotometer that showed the peak at 575 nm. Size and distribution of the biosynthesised SeNPs were analysed by HR-TEM that showed the formation of particle size in the range of 100-250nm. The synthesised SeNPs showed good cytotoxic activity against HT-29 cell line with 40.5%, 33% and 23.7% of cell viability at 2μg/ ml, 4μg/ml and 30μg/ml concentration respectively. Conclusion: The present study reports the simple and eco-friendly synthesis of SeNPs that showed good cytotoxic activity against HT-29 cell line suggesting that biogenic SeNPs could be a potential chemotherapeutic agent.
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Formulation and Evaluation of Niosomal in situ Nasal Gel of a Serotonin Receptor Agonist, Buspirone Hydrochloride for the Brain Delivery via Intranasal Route
Background: Buspirone Hydrochloride is an anxiolytic agent and serotonin receptor agonist belonging to azaspirodecanedione class of compounds used in the treatment of anxiety disorders. It has short half-life (2-3h) and low oral bioavailability (4%) due to extensive first pass metabolism. Objective: The nasal mucosa has several advantages viz., large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism and ready accessibility that lead to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel. Method: Buspirone hydrochloride niosomal in situ nasal gel was formulated, optimized and evaluated with the objective to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimized using32 factorial design. Niosomes were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for the formation of in situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6. Result: The vesicle size of all niosomal suspension batches ranges between 168.3 -310.5 nm. The vesicle size of optimized niosomal suspension F5 batch is 181.9±0.36nm. For F5 batch, the value of zeta potential was found to be -15.4 mV; this specifies that prepared niosomes have sufficient surface charge to prevent aggregation of the vesicles. % entrapment efficiency for all batches was found in the range 72.44±0.18% to 87.7±0.66%. The cumulative percent release of niosomal suspension ranges from 66.34±0.39 to 84.26±0.26%. Ex vivo permeation of Buspirone hydrochloride through the sheep nasal mucosa showed that 83.49% w/w drug permeated after 8 h. The SEM and Zeta potential studies showed the formation of stable vesicles. Conclusion: Thus, the application of niosomes proved the potential for intranasal delivery of Buspirone hydrochloride over the conventional gel formulations. Overall intranasal drug delivery for Buspirone hydrochloride has been successfully developed.
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