Recent Advance in Surfactant Vesicles Niosome for Delivery of Therapeutics and its Application
Stanekzai Azimullah1, Sudhakar CK2, Ashish M2
Assistant Professor at Kabul University, Faculty of Pharmacy, Department of Pharmaceutics.
Assistant Professor at Lovely Institute of Technology (Pharmacy) School of Pharmaceutical Sciences Lovely Professional University Phagwara, Punjab.
*Corresponding Author E-mail: azimullah1984@gmail.com and Sudhakar.20477@lpu.co.in
ABSTRACT:
Surfactant are surface-active agent, which reduce or lower the interface tension between two phase systems. Such concept were utilized in the drug delivery, surfactant vesicles (SV) niosomes. Niosomes are second generation of liposome which slightly different in composition of liposomes. Surfactant play significant role for noisome formation and utilization of different surfactant can possess different properties depending upon the surfactant such as bola surfactant, gemini surfactant. Bola surfactant niosomes have been used as topical for the treatment to skin cancer. Gemini based surfactant niosomes they are main comprised of amino acid-based surfactants and they have shown good penetration enhancer of drug into the skin. Gemini based niosomes able to delivery of anti-diabetics, chemotherapeutics, analgesic and antibiotics to treat different diseases. Surfactant vesicles are more prominent in delivering the drugs in controlled manner to skin through topical and transdermal route.
KEYWORDS: Surfactant, Niosomes, Transdermal System, Application.
Transdermal and Dermal drug delivery is a controlled release system which is release the drug over the skin to get systemically therapeutic effect (Thong et al., 2007). Skin of the human body is the largest and multi-function organ, it is an available route for delivery of local and systemic drugs, which is minimized the side effect of the drugs associated by parenteral and oral routes. The advantages of skin delivery is, avoid first pass effect, well patient compliance, prevent irritation of drug on GIT system and stomach ulceration (Barry 2001). One of the major limitation of transdermal delivery is, less permeation of hydrophilic active agent over the skin due to stratum corneum which is consist of corneocytes and fixed by fat matrix (Schreief and Bouwstrab 1994).
In last decade’s number of physical, (Iontophoresis, Sonophoresis, Electro osmosis, Temperature and Electroporation) and Chemical (Sorption prometers and
Accelerants) approaches developed to enhance the penetration of drug molecules across to the barrier of skin (Rastogi and Singh 2005). Vesicular structure able for transdermal delivery because it has several advantages such as no-toxic, biodegradable, amphiphilic nature and improve the drug bioavailability. Furthermore can modified the structure appearances such as shape, size, nature of lamellae and their composition (Agarwal et al., 2001). Delivery of NASSIDs over the oral rout is more effective, because delivery of NASIDs orally makes gastric irritation and ulceration hence transdermal delivery of NASIDs through the skin is a technique which can prevent above side effects and maintain the plasma level after administration of single dose for a long duration of time (Berba et al,. 1991).
2. NONIONIC SURFACTANT VESICLES:
Niosomes are grown from liposomes, niosomes are non-ionic single-chain surface active agent vesicles which are combination of cholesterol and other components such as stabilizer (Schafer-Korting 2010). Niosomes are like liposomes with amphiphilic double layer structure, it’s prepared as a unilamellar or multilamellar vesicles (Pola Chandu 2012). Chemical strength due to oxidation resistant, cheaper and permeation characteristics of niosomes are higher than liposomes (Nasr 2008). Niosomes have high capacity to incorporated large amounts of drugs, biocompatible, biodegradable, non-toxic, nonimmunogenic, controllable properties like size, shape, lamellarity, easy storage and handling, control release of drugs and applicable from different routes of administration. However niosomes are physically instable system than liposomes, therefore during suspension may aggregation, hydrolysis, leakage, limited drug loading and shelf life occurs (Hamishehkar et al., 2013). There are number of mechanism explained capability of niosomes to increase the active ingredients among the skin such as diffuse as whole, formation very small vesicle in the skin, interaction with stratum corneum of skin barrier due to high concentration and non-ionic surfactant enhance the penetration of the drug (Sezer 2012). In 1997 L Oreal reported the application non-ionic surfactant vesicles in cosmetics formulation (Handjani 1979). Lancome, part of Oreal group in the 1980 marketed as anti-aging and whitening products (Date et al., 2006). Recently researchers formulated Resveratrol as niosome for dermatological application (Abdelbary and AbouGhaly 2015).
3. MECHANISM OF SURFACTANT WITH SKIN AND PERMEATION OF DRUGS:
The particular mechanism of permeation of active ingredients in the small vesicles over the skin are not until now discovered, but the permeation is related on the physicochemical characteristics of the active molecule, vesicles formation and hydration temperature for formation of niosomes (Fig.1). The lipids which are used in the manufacturing of proniosomes, play role as carrier and sustained the carrier on the site of action (Kiran Yadav et al., 2010). Rate-limiting stage in the permeation of active ingredient over the delivery of drug through the dermis, is the zone of stratum corneum, which is packed strongly as double layer by hydrogen bonding. The bonding of hydrogen will reinforce and stabile the lipid double layer and outcome may impart the barrier characteristic of stratum corneum (Junyaprasert et al., 2008).
4. CARRIER BASED TRANSDERMAL AND TOPICAL DRUG DELIVERY SYSTEM:
Vesicular carriers are usually used for transport of transdermal and topical drugs. They are characteristically consist of biocompatible and biodegradable lipids and water phase (buffer solutions, or cosolvents). The structure of lipids consist of concentric lamellae which are entrapping the water phase, these carriers can supposedly divider into the skin stratum and able to transport the active ingredient across the stratum corneum. In addition, the size of small vesicles are in nano range, hence the drug loaded in vesicular carrier can easily permeate through the skin. When the vesicle size is 600 nm it is impossible to enter the deeper stratum of the skin, it will stay on the skin barrier (stratum corneum), while if the vesicles size is 300 nm can easily able to enter more and deeply, however vesicles with 70 nm size range can able to deliver the epidermal and dermal layers (Verma et al., 2003). For enhancing the skin penetration potential, investigators have created and modified different vesicular carriers with specific fundamental and functional characteristics in the latter four decades. The first-lipid based vesicular carrier was known liposome. For transdermal and topical drug delivery, classification of carriers shown in figure 2 (Mezei and Gulasekharam 1980).
5. APPLICATION OF SURFACTANT BASED VESICLES:
Surfactant based drug delivery system is practicable for number of pharmacological ingredients for their act against numerous illnesses, niosomes are presently as a multipurpose drug delivery system with many pharmacological and pharmaceutical used, therefore Nano niosomes are applicable from different route of administration such as: parenteral, oral, transdermal, pulmonary, vaginal, ocular, nasal and etc.
5.1 Application of niosomes as oral drug delivery:
Oral drug delivery deal with number of problems, like being of acids, enzymes in the stomach fluid and intestine, low absorption, and variant bioavailability of active ingredient. Hence, to increase the bioavailability, drugs formulated as a niosomes which are called a novel drug delivery system. The first oral niosomal drug delivery was described by (Azmin et al. (1985). And methotrexate formulated as niosome. The niosome formulation effectively improved bioavailability of methotrexate. Other drugs also formulated as Niosome for example Ganciclovir niosome consist of Span 40, Span 60, and cholesterol. In vivo studies in rats shown an effective improvement in the bioavailability of the drug after oral administration when compared with tablet form of same drug (Akhter et al., 2012). Similarly, another study pointed that noisomal formulation enhanced the oral bioavailability of Cefdinir which is related to BCS class IV (Bansal et al., 2013). Finally the study shows, Candesartan Cilexetil niosomal formulation, improve the oral bioavailability of drug which is low water soluble. The drug release from niosome formulation increase when compare the same drug of conventional dosage form (Bayindir et al., 2015).
5.2 Targeted and Anti-cancer drug delivery system:
Nano carrier vesicles inhibit the reticulo-endothelial system (RES), the circulating serum issues called as opsonins, which are mark them for clearance. Therefore such localized active agent delivery have been subject in management of animal tumor cells and also applicable for treatment of liver and spleen metastasize. Anticancer drugs by using niosomal vesicular system have number of advantages like decrease the organ toxicity (Brien et al., 2004), increase antineoplastic effectiveness (Bayoumi and Torchilin 1980), prolonged and controlled release of drug from vesicular carriers in systemic circulation (Cosco et al., 2009) and reduce mortality in patients (Hamilton et al., 2002). On the important pharmaceutical and clinical truths, innovative niosomes prepared of α,ω-hexadecyl-bis-(1-aza-18-crown-6) (bola), Span 80 and cholesterol (2:5:2) were formulated as appropriate transport systems for application of 5-fluorouracil (Bayoumi and Torchilin 1980). Magnetic drug delivery target the exact tissue or organ is, suggested on the assumption which is magnetic playing field are not hurtful to biological systems. Ribavirin vesicles are formulated by hand shaking hydration technique using Span 60, cholesterol, and DCP to target liver tissues (Hashim et al., 2010). Researchers found that the niosomal vesicular system meaningfully improved ribavirin liver concentration when comparison with free solution of ribavirin drug (Mukherjee et al., 2017).
5.3 Surfactant based vesicle for delivery of peptide drugs:
Surfactant based vesicles are able to deliver 9-desglycinamide, 8-arginine vasopressin for oral administration. In vitro model study shows when the above drug formulated as niosomal vesicles, the stability of drug increases in GIT fluid. Niosomal vesicles are reported as a strong adjuvant with low toxicity and high stability in the term of immunological selectivity (Moser et al 1989).
5.4 Niosome as a carrier for hemoglobin:
Hemoglobin and albumin are the major protein in the human circulation system. For those patient which are suffering to anemia, niosome used as a carrier for delivery of hemogolobin. Niosome vesicles are alike penetrable to oxygen and hemoglobin separation curve can be reclaim non-encapsulated hemoglobin (Jayaraman et al., 1996).
5.5 Transdermal drug delivery by niosomes vesicles:
Transdermal niosome increase the permeation rate of drug which is combined in niosomes, the low penetration of active ingredient over the skin is, the main problem of transdermal drug delivery further dosage forms. For example the delivery of erythromycin through the skin as a niosomal formulation (Brewer and Alexander 1992). Delivery of drug through the skin reduce active agent from the first-pass metabolism. The highest benefit of a transdermal drug delivery over other drug delivery, provides a controlled release of the active ingredient into the place of action. The major drawback of transdermal delivery is the skin barrier, thus only small active particles are capable to penetrate the stratum corneum barrier of skin. Therefore the intercellular fat barrier in the stratum corneum is very loose to penetrable beside of vesicles.
5.6 Localized action:
Loaded of drug through the small vesicles is one of the methods to reach localized active agent action is size, low permeability and connective tissue through the epithelium keeps the drug localized at the site of application. Localized action outcomes in improvement of effectiveness of potency of the active agent and at the similar time decreases the systemic toxic effects, for example anti monials encapsulated within vesicles are taken up by mononuclear cells resulting in localization of active ingredient, enhance the potency and therefore reduction dose as well as toxicity (Chauhan and Luorence 1989). The assessment of surfactant based vesicular drug delivery system is till now at a beginning stage, but vesicular drug transport has shown potential in tumor chemotherapy and anti-leishmanial treatment (Suzuki and Sokan 1990).
5.7 Niosomes application in vaccine delivery:
Growth of novel safe and effectivness vaccines is a significant aim for several investigation groups in all over the world. DNA of different microorganism are harmless than live microorganism-based vaccines it may be show low efficiency. The practice of adjuvant system has confirmed to improve the immunogenicity of these subunit vaccines by protection (i.e. preventing degradation of the antigen in vivo) and improved the targeting of these antigens to professional antigen-presenting cells (Obrenovic et al., 1998). Brewer and Alexander (Brewer and Alexander 1992) described the first use on vesicle antigen transport for immunization of Balb/c mice beside bovine serum albumin (BSA). They assumed that vesicles were actually better stimulators of the lymphocyte subset than was Freund's complete adjuvant and by inference, potent stimulators of cellular immunity (Hassan et al., 1996), showed well immunogenicity with herpes simplex virus- 1 antigen encapsulated in 1-mono palmitoyl glycerol cholesterol/DCP nonionic surfactant vesicles in mice. Incomplete protection against homologous (type 2 herpes simplex virus) challenge infection afforded to mice by HSV-2 antigen encapsulated niosomes (Mohamedi et al., 2002). Displays the significance of structure and technique of niosomal adjuvant formulations. Formulated Span, cholesterol and DCP niosomes having tetanus toxoid emulsified in an external oil phase to form a vesicle-in-water-in-oil (v/w/o) formulation. The basic in vitro studies shown the using of cottonseed oil as the external oil phase, presented improved immunological action over the free antigen or small vesicles (Yoshioka et al., 1995).
5.8 Niosome application for pulmonary delivery:
Delivery of the active molecules to the lungs appears to be an attractive plan due to the great surface area of the alveolar region (Kurmi et al., 2010). Nano vesicles should be capable for safety and effective delivery of unlike therapeutics to respiratory tract. Beclometasone dipropionate formulated as proniosomes, which is used as anti-asthma steroid. Proniosomes formed by coating sucrose particles by Span 60 and cholesterol to form nano-sized lipid based vesicles, were formulated through hand shaking technique and finally used of sonication for reducing the size of prepared proniosome (Elhissi et al., 2013).
5.9 Niosome application for nasal delivery:
For transport of therapeutic moieties to the brain, blood brain barrier limits the penetration of drug across to the brain. Therefor intranasal route directly deliver drug to the brain without blood brain barrier and systemic absorption. Hence escaping the adverse effect and enhancing the efficacy of neuro therapeutics. Novel drug delivery like nanoparticles, liposomes and niosomes have noble characteristic to target the brain and minimize toxicity of the nasal mucosa and central nervous system (Brain Facts 2014). Classification of nasal drug delivery system shown in Figure 3.
6. CONCLUSION:
This review suggest a broad description on the chemical arrangement, structure, benefits, and uses of vesicles, their character as transdermal penetration enhancers, and novel uses as delivery systems for transdermal medicine targeting. Nonionic surfactant based vesicles have been confirmed to be hopeful controlled drug delivery systems for transdermal and dermal application of both hydrophilic and hydrophobic pharmaceutical active ingredients. The potential of nonionic surfactant vesicles can be improved by applying novel formulation, loading, and adjustment approaches. These areas requirement further investigation for the improvement of niosomal arrangements it can be prepared commercially accessible. Investigators must be aware in the necessity for suitable choice of appropriate surface active agents for preparation of nonionic surfactant based vesicles, type of surface active agents used in the formulation of niosome is the main factor for determining the prevalent formation of niosome vesicles, with their toxicity, constancy, and possible uses.
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Received on 30.05.2019 Modified on 05.06.2019
Accepted on 30.07.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2020; 13(4):1995-1999.
DOI: 10.5958/0974-360X.2020.00359.5