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The role of nanoemulsions in vaccines, adjuvants, anti-infectives and dermatological treatments
By Drs. Susan Ciotti and Robert L. Hagan
The pharmaceutical industry continues to struggle with bringing new, commercially viable therapies to market. As with other industries, there is a pressing need to differentiate new products and improve existing product lines. Healthcare providers and consumers continue to demand new, more effective therapies, while at the same time focusing on cost containment and reducing time-to-market.
Ground-up development of new chemical entities with standard delivery systems, such as tablets and capsules for oral drugs and lotions and creams for topical indications, represents the traditional pathway for new products. Employing novel technologies to deliver new chemical entities is worth evaluating during the discovery phase and at the onset of new product development.
Likewise, older products can be revitalized by employing novel formulations and delivery systems. Delivering the required amount of active compound in a unique, cost-effective, commercially viable and consumer-friendly fashion is one thing; achieving the same efficacy and enhanced safety with an even lower dose of the active compound is particularly appealing. New drug delivery technologies can bring new life to older therapies, and even make new molecules with challenging physicochemical characteristics attractive, both commercially and therapeutically.
One relatively new means of enhancing delivery is employment of therapeutic nanoemulsions during discovery and formulation development.
Therapeutic nanoemulsions are oil-in-water emulsions with average droplet sizes of 400 nanometers. There should be no confusion of nanoemulsions with nanoparticles used in other realms of nanotechnology. Nanoemulsions are composed of safe, well-characterized ingredients, combined in a proprietary manner to yield a stable emulsion. The unique size range of therapeutic nanoemulsions allows the droplets to traverse the pores and hair follicles of the skin and mucosal membranes, without disrupting normal tissues.
Nanoemulsions are effective in their own right against certain bacteria, fungi and viruses. These droplets accumulate in the epidermis and dermis, where they interact directly with and disrupt organisms at the site of the infection. Nanoemulsions can also act as mucosal vaccine adjuvants. As with adjuvants in general, nanoemulsion adjuvants offer the possibility of achieving immunity with less antigen. Clinical studies are ongoing to further assess the applicability of nanoemulsion as topical anti-infectives and mucosal vaccine adjuvants.
The dermal/topical route of administration is particularly attractive for employing nanoemulsion-based delivery systems. Encapsulation using nanoemulsion systems is an increasingly implemented strategy in drug targeting and delivery. Such systems have also been proposed for topical administration to enhance percutaneous transport into and across the skin barrier. However, the mechanism by which such particulate formulations facilitate skin transport remains ambiguous.
Studies using fluorescent microscopy were used to visualize the distribution of fluorescent nanoemulsions across human and porcine skin. The images revealed that nanoemulsions accumulated preferentially in the hair follicle openings and traverse these openings to penetrate the surrounding tissues.
This unique, translateral delivery of topical agents will potentially enhance the efficacy of many drugs, particularly those with a mechanism of action that requires the active compound be localized to certain parts of the skin. Treatment benefits may be realized in acne, for example. Retinoids and other compounds that target acne treatment, would benefit from nanoemulsion-based delivery.
Nanoemulsion- based delivery systems could be superior to conventional topical dosage forms, such as ointment and gels, in several respects. Nanoemulsions typically exhibit a low potential for skin irritation. Nanoemulsions can increase the solubility of drugs exhibiting poor water solubility through entrapment in the core of the nanoemulsion droplets. Drug stability is always a concern in product development. Drugs that show promise at the discovery stage can be problematic to develop into commercially viable products due to stability concerns. Nanoemulsions could enhance the stability of chemically unstable compounds by protecting them from oxidative degradation and degradation by light, for example.
Nanoemulsions can aid in transporting agents to the target area. Liposomes have been investigated extensively for their ability to transport drugs to target areas. Lipososmes also have utility in reducing dermal side effects and in improving photostability of light-sensitive compounds. However, the cost associated with these complex liposome systems and their inherent physical instability can limit their utility and commercialization.
Topical delivery using nanoemulsions may achieve the same benefits as liposomes, such as reduced side effects and improved physical stability, but at a much lower cost compared to liposomes due to the relative ease of scale-up and manufacturing of nanoemulsion-based formulations.
Nanoemulsions can possess inherent anti-infective properties, with the ability to kill pathogens, such as those present in wounds. The process by which nanoemulsions kill pathogens is not chemical, as with other types of antibiotic treatments, but by physical disruption of the cell wall and subsequent lysis of the organism. When nanoemulsion droplets encounter lipids on a bacterial cell wall or a virus envelope, for example, the surface tension of the nanoemulsion droplets forces the lipids of the organism and oil contained in the nanoemulsion droplets to merge. On a mass scale, this merging effectively disintegrates the membrane and kills the pathogen.
Combining this inherent ability of nanoemulsions to kill certain pathogens by physical disruption with anti-infective compounds possessing other mechanisms of action may result in products with unique anti-infective properties, enhanced efficacy and greater safety.
Adjuvants in general are substances that enhance the effect of vaccines. Nanoemulsion-based adjuvants offer the possibility of non-irritating, needle-free vaccines, administered as nose drops or by a simple nasal sprayer. The nanoemulsion is uniquely capable of permeating the nasal mucosa, where it loads vaccine antigen into immune-presenting cells. These cells then carry the antigen to areas of the body that initiate an immune response, including the lymph nodes, thymus and spleen producing both mucosal immunity and systemic immune response. Hot brunette teen Vlada gets her ass stretched Hot Ebony Riding Dildo Sexy nurse pleases her pussy with her panties Fucking Hot Mila Blaze and Her Sexy Voice Is Sure To Make You Hard Sexy nurse treats horny patient White guy is sticking his cock inside a black babe teen fucks big black dildo cums hard Watch the best porn videos available on the internet https://www.pornjk.com/tags/thumbzilla/ Blowjob Stella Cox getting BBC Anal Gloryhole Karma Rx gets assfucked by Markus Dupree Gia Steel and her gf rides cock one after another Pornjk.com - XXX Video HD, XXX HD Porn Tube, Pornjk Porn, Hot HD Video, Free XXX Pornjk Porn Videos
As with adjuvants in general, nanoemulsion adjuvants offer the possibility of achieving immunity with less antigen. However, nanoemulsion adjuvants take the antigen-sparing concept a step further. Recent experiments conducted in ferrets with a nasally administered nanoemulsion-adjuvanted vaccine for seasonal influenza elicited a robust immune response with only about one-fifteenth the antigen used in a typical injected dose. This animal study also demonstrated an important distinction between traditional vaccines and nanoemulsion-adjuvanted vaccines. Traditional injectable vaccines afford one type of immunity, commonly called systemic immunity.
Results indicate that nanoemulsion adjuvant-based vaccines can impart a second type of immunity, known as mucosal immunity, in addition to the systemic response. The end result is a more robust immune response following vaccination, and therefore enhanced disease protection, particularly in cases where the route of infection is via the nose.
Nanoemulsion-based, intranasal vaccines have elicited robust immune responses in animals vaccinated against influenza, pneumoncoccal, hepatitis B, HIV, RSV, anthrax, smallpox, cancer and other diseases. In some cases, the immune response is exponentially higher than what is required to provide adequate protection against infection.
Large pharmaceutical companies have recognized the benefits of nanoemulsions and are licensing proprietary therapeutic nanoemulsion-based formulations to create novel treatments. Nanoemulsion-based delivery platforms can increase the effectiveness of new compounds, or bring new life to existing product lines. Enhanced safety margins and reduced cost are potential additional benefits of nanoemulsion-based formulations. A change is needed in the current drug discovery and development paradigms. Nanoemulsions represent an important opportunity for companies to make a change and bring new, viable, consumer-friendly products to market.
Dr. Susan Ciotti is director of formulation R&D at NanoBio Corp. Prior to joining NanoBio in 2007, Ciotti held formulating positions at Pfizer Inc. and Johnson & Johnson. Ciotti currently serves as an adjunct professor at the University of Michigan College of Pharmacy.
Dr. Robert Hagan is senior manager of supply chain at NanoBio Corp. Before joining the company, Hagan held numerous positions within Pfizer, Pharmacia Corp. and Warner-Lambert/Parke-Davis. He also served as an officer with the U.S. Air Force from 1990-1996.