Sidharth Mehta

1Guru Jambheshwar University of Science and Technology,Hisar 125001,India.

Abstract

Key words:Nanocarriers,Niosomes,Anticancer drugs,Targeted drug delivery,Non-ionic surfactants vesicles,Antineoplastic agents

Background

Like other diseases such as acquired immune deficiency syndrome and tuberculosis,cancer is also one of the diseases which has a high mortality rate across the world.It includes strange cell development with the likelihood to spread to various parts of the body.It causes deregulation and mutation of genes [1].Around 2015,about 9.05 crores of people had malignant growth.About 1.41 crores of new cases happen in a year (excluding skin cancer).The mortality rate due to cancer is 15.7% of all cases.The most widely recognized kinds of cancer in masculine are prostate,lung,stomach and colorectal cancer.While in women,the foremost frequent types are breast carcinoma,lung and cervical cancer.

A lot of treatment options are available for cancer.Chemotherapy is the term associated with the management of cancer with one or more antineoplastic drugs (chemotherapeutic agents) as part of a standardized regimen.Traditionally,anti-neoplastic agents act by slaughtering cells that split up rapidly,a censorious property of most cancerous cells.Regardless of whether the cancer cells are intrinsically more endangered than normal cells to the outcome of anti-neoplastic agents,the drugs are aimless and also can cause injury to some extent to normal tissues.The anti-tumor systemic treatment brings many side effects,such as bone marrow suppression,hair loss,fertility impairment,nausea and vomiting et al.These days endeavors are centered on efforts to terminate cancerous cells by specific targeting while frugal normal cells.To accomplish these goals,the thought is the advancement of new transporters for both existing and new medications and characterizing better therapeutic targets relative to the molecular changes in the cancer cells and their vasculature [2].One such approach is the development of the vesicular drug-delivery system in which anti-cancer drugs can be incorporated within the vesicle,irrespective the drug is either hydrophilic or hydrophobic in nature and by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.

Niosomes are the sort of non-ionic surfactant vesicles,which are biodegradable,non-toxic,more stable,and modest,another way to deal with liposomes [3].Liposomes were the first lipid nanocarriers that were developed by researchers.however,they have a couple of inconveniences like low bioavailability,toxicity and stability issues.Due to the aforementioned disadvantages of liposomes,researchers try to another nanocarriers and hence niosomes were discovered [4].Niosomes exist either as unilamellar,oligolamellar or multilamellar [5].Niosomes are also known as non-ionic surfactant vesicles,because they are formed of non-ionic surfactants and these surfactants are also non-toxic in nature.Niosomes may also consist of cholesterol or its derivatives and charged molecules,in addition to nonionic surfactants.Stiffness to niosomes could be provided by cholesterol and preparation got stabled by added charged molecule like phosphatidic acid (negatively charged).Niosomes are extensively known to incorporate both hydrophilic as well as lipophilic drugs in it with an extended range of solubility [6–9].

Drugs can be conveyed via.niosomes in a synchronous manner,for instance,doxorubicin and curcumin (CUR,anticancer drugs) [10].Niosomes can be used to deliver drug via ocular delivery (eg.tacrolimus,naltrexone HCl) [11,12],transdermal (eg.gallidermin,clomipramine) [13,14],pulmonary (eg.glucocorticoid) [15],oral (eg.cefdinir) [16,17] as well as they can be used to deliver drug across blood-brain barrier (eg.temozolomide) [18].

Assembly of niosomes

As mentioned above,niosomes are composed of nonionic surface-active agents and when these surfaceactive agents come in contact with aqueous media,they self-assemble themselves and form a bilayered assembly.These bilayered assemblies formed are thermodynamically stable only when surfactants and cholesterol are blended in an appropriate extent,and the temperature must be above the gel liquid transition temperature [5,19].Beacuse of the presence of nonionic surfactants in niosomes,there is better targeting of drugs to brain,liver and tumor.This bi-layered structure contains a space in the inside.Because of their spatial geometry niosomes can incorporate hydrophilic as well as lipophilic drugs in their structure.Entrapment of hydrophilic drugs in niosomes can occur in the central aqueous domain or it can be adsorbed on the bilayer surface whereas hydrophobic drugs enter the bilayer structure by partitioning into it [5,9].

Advantages and disadvantages of niosomes

Niosomes offer a few favorable circumstances over the conventional drug delivery system.Niosomes when contrasted with liopsomes,offer much chemical stability,higher bioavailability and longer shelf life;surface of niosomes can be easily modified by incorporating various functional groups over its hydrophilic head to make targeted drug delivery;since niosomes carry no charge on its surface,it is likely to be more compatible and less toxic;offers high drug payload capacity;easy scale up from laboratory to industry;niosomes are composed of non-ionic surfactants,hence these surfactants are biodegradable in nature and also cannot cause any immunogenic reactions;both hydrophilic and lipophilic drugs can be incorporated into niosome vesicles;niosomes have a tendency to improve the bioavailability of active pharmaceutical ingredients by enhancing physical and biological stability;niosomes can be given practically to all routes of delivery,for example,oral,parenteral,transdermal,ocular,and pulmonary;niosomes can be used for targeted,controlled as well as sustained delivery of a drug [3,6,9,20,21].

Despite there are various advantages of niosomes but stability could be an issue with the aqueous dispersion of niosomes because the drug may get hydrolyzed.Niosome’s main component being surfactants,and these majority of these having sensitizing action.The problem of drug leakage from the entrapment site and aggregate formation of niosome may also occur.[9,21,22]

Latest illustrations of delivery of anticancer drugs via niosomes

Targeted delivery of anticancer drugs can be accomplished utilizing niosomes.This targeting could be passive [23] (deposition of niosomes within the tumor because of the special properties of the tumor cells not existing in the normal cells) [24],physical (delivery based on specific environment conditions like pH or magnetic fields) [22] or active type [23] (active uptake of niosomes by the tumor cell).The active targeting can be accomplished either by modifying the structure features of the surface or by attaching the ligand to the nisomes.For ligand attachment either cholesterol-polyethylene glycol (PEG)-ligand conjugate be incorporated to the niosomes or it can be attached to cholesterol or to the end of the PEG chain.

Oral delivery of paclitaxel using niosomes.

Bayindir et al.formulated a well-known anticancer agent,paclitaxel (PTX) niosomes in order to enhance its bioavailability utilizing various surfactants (Tween 20,60,Span 20,40,60,Brij 76,78,72) by film hydration strategy.PTX discharged from niosomes by a mechanism of diffusion-controlled.The slow discharge saw from these formulations may be helpful for diminishing the toxic side effects of PTX.They also evaluated that niosomes also have the efficiency to protect PTX against gastrointestinal enzymes (trypsin,chymotrypsin,and pepsin) on oral delivery [25].

PEGylated niosomes as a delivery system for gambogenic acid

Lin et al.prepared PEGylated niosomes of gambogenic acid from biocompatible non-ionic surfactant (Span 60),cholesterol and dicetyl phosphate by the improved ethanol injection technique,and were modified with a PEG monostearate15 (PEG15-SA).PEG15-SA,as a biocompatible,non-toxic and non-immunogenic hydrophilic segment,was grafted onto the surface of colloidal niosomes carries to reduce the uptake by the reticuloendothelial system,prolonging the circulation time and attaining higher entrapment efficiency.These PEGylated niosomes are used as the carrier for anticancer therapy and to enhance the stability of gambogenic acid [26].

Self-degrading niosomes for multidrug delivery

Sharma et al.prepared self-degrading niosomes for multidrug delivery.In this work,niosomes were prepared by using two active molecules CUR (hydrophobic) and doxorubicin hydrochloride (hydrophilic) for cancer treatment and showed that CUR is supposed to accumulate in the shell whereas,doxorubicin accumulates in the inner aqueous core of the niosome.They observed 2 release phases;in the initial phase release of doxorubicin was observed for the first two days and then CUR was released for 7 days.Synergistic cytotoxic effect was observed against HeLa cell lines [27].

Morusin loaded niosomes for potentiation of anticancer therapy

Agarwal et al.prepared the noisome of morusin for potentiation of anticancer herapy.He observed a pHdependent release of the drug.At pH 7.4 release of morusin from niosomes was less as compared to the release at pH 4.5.After 120 h the drug release was 58.1% in acidic conditions,pH 4.5 whereas at physiological pH 7.4 only 43.3% release was obtained.It indicates high drug release can be obtained in the acidic conditions of the cancer cells [28].

Capecitabine loaded nanoniosomes for anticancer therapy

Capecitabine (CAP) is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers.However,there are some side effects and chemoresistance limiting its use.Formulating nano-carriers can increase the efficacy of anticancer drugs.Vanani et al.prepared nanoniosomes of CAP by the method of thinfilm hydration.The nanoniosomes with an amphipathic structure can penetrate into the cells with an enhanced release rate [29].

Cationic PEGylated niosomes for Coadministration of PTX ＆CUR for anticancer therapy

Alemi et al.loaded both CUR and PTX into cationic PEGylated niosomal formulations for enhanced efficacy in MCF-7 human breast adenocarcinoma cells.PTX is an important antineoplastic drug,and it is isolated from the bark of Hongdoushan (Taxus brevifolia).PTX demonstrates an effective chemotherapeutic and cytotoxic activity against breast,ovarian,colon,lung,prostate,and brain cancers.However,the wide therapeutic effect of PTX is limited due to the low therapeutic index and poor water-solubility.CUR is a hydrophobic polyphenol compound obtained from the rhizome of the plant Jianghuang (Curcuma longaL.).CUR has been demonstrated to be highly effective against a variety of different malignancies,including leukemia and lymphoma,as well as colorectal,breast,lung,prostate,and pancreatic carcinoma.However,the pharmacological application of CUR has been impeded due to its extremely low aqueous solubility,instability of extremely poor bioavailability,and high metabolic rate.As a result,nano-carrier formulation i.e.niosomes of PTX ＆CUR were prepared to overcome these above-mentioned limitations.To improve stability and circulation half-life,niosomes may be coated with appropriate polymer coatings,such as PEG,creating PEGylated niosomes.PEG coating also helps reduce systemic phagocytosis,which results in the prolonged systemic circulation,as well as reduced toxicity profiles.

Conclusion

The surfactant nanoparticles like niosomes has always been a potential carrier system for both hydrophilic or lipophilic drugs with good therapeutic applications.The purpose of this work was to highlight the role of non-ionic surfactant vesicles as a novel drug delivery system for various categories of anticancer drugs.They are the new generation.Smart delivery devices offering for high drug payload capacity,modulated drug release,modify drug distribution in the body and release profile of an associated drug.Their application and efficiency in protein and peptide drugs,gene delivery systems and other fields still need to be better exploited.