INTRODUCTION:

Skin cancer is harmful disease which is classified into two categories one is known as melanoma skin cancer (MSC) and the second type is known as non-melanoma skin cancer (NMSC). The non-melanoma type of skin cancer is the main classified cancer in worldwide¹, also melanoma type skin cancer MSC causing huge amount of deaths.² In non-melanoma skin cancer the basal cell carcinoma (BCC) or the cutaneous squamous cell carcinoma (cSCC) reported for 99%.

Conventionally, (cSCC) is responsible for 20% of all skin cancers and the majority of the cancer is accumulating by BCCs. Furthermore, a fresh study predictable the occurrence of BCC and SCC in ratio of 1:1 from population surveys.³ During the study it has found to be the increase rate of cSCC was observed in a period of 1976-1984 and 2000-2010.⁴

Human skin is the largest organ of body and it acts like a protective barrier to save the skin from harmful radiations, chemical exposures, and other microorganism. The properties of skin are to prevent from the loss of salt and fluid, also it helps to regulate the body temperature. Topical route of drug delivery through skin is important and helpful delivery route for targeted therapies and bypass the first-pass metabolism subsequent by oral delivery.⁵ Drugs by topical delivery have great benefit in treating clinical and subclinical lesions from a large surface area of the body.⁶

Now a days, huge advancements have been developed for drug delivery, & the attractive and best suitable delivery strategy is Nanoparticles. Nanoparticles were used to deliver the therapeutic agents by topical route. The system of Nanoparticles were developed to overcome the biological barrier for targeting the tumor sites, These systems can be developed to overcome biological barriers & to target drug delivery to the tumor sites, by use of less dose and to minimize the side effects.^7,8 The use of Nanoparticles in cancer treatment is highly dem&able, many of the approaches for Nanoparticles are under research & few of them are reached their parameters of study or already available in the market. Nanoparticles are useful to increase the potential of drugs and their bioavailability with the therapeutic usefulness & to improve the patient compliance in the delivery of drugs.^9,10 While the delivery of drugs through Nanoparticles will increase the kinetics of release & drug retention on skin.

Nanotechnology approaches are useful to enhance the delivery of drugs in cancer treatment. The main aim of review is to discuss about the basic fundamentals of cancer with relate to dermal delivery of drug through Nanoparticles.¹¹ The nanotechnologies for dermal delivery of drugs were explained for their effective tool for skin cancer.^12,13,14 Clinical management & the skin penetration pathways were explained to underst& the basic mechanism of drug permeation through skin. Some of the available treatments were discussed in clinical management of skin cancer. The design, structure or morphology of Nanoparticles & therapies for cancers treatments with their physical methods in combination with other anticancer agent with multifunctional delivery systems will summarized in this review article.

The Skin: A Targeted Organ:

Skin the vital organ of human body. The surface area of skin is estimated around 1.8 mt² which covers 16% area of body. The human skin consist of three layers epidermis, dermis and subcutaneous. SC layer is 2-10µm thick, the subcutaneous layer is the healthy skin & it provides a obstruction to the passage of hydrophilic & large molecule size drugs. The suitable molecular weight for the delivery of drug through skin is 500 Dalton sizes.^15,16 The subcutaneous layer is directly followed by the epidermis layer and composed of viable keratinocytes followed by the dermis comprising of fibroblasts and onnective tissue. The dermis layer consists of sweat glands, sebaceous glands, hair follicles, lymphatic vessels, blood vessels, and nerve fibers. Nanoparticles that penetrate into the epidermis have access to viable and immunologically active cells and could transit into the lymph nodes.

Figure 1: Structure of the Skin Barrier. The epidermis, which forms the skin’s outer surface or barrier, is made of the hydrophobic stratum corneum (SC), the viable epidermal layer, followed by the dermis.

Skin Penetration Pathway for Nanoparticles:

There are two possible routes of drug penetration through skin, called as Transepidermal & transappendegeal pathways, which have been diagrammatically represented in Figure 2. These pathways involve the passage of molecules through the skin.^17,18

Transepidermal pathway

Transcellular route requires the permeant pass through of alternating the layers of cells and extracellular matrix. This penetration of drugs through this route is by crossing the hydrophilic & lipophilic barriers. Some hydrophilic drugs follow the transcellular pathway while lipophilic drugs favor the intercellular route of drug penetration. In the Transepidermal pathway drugs are easily crossing the phospholipids membrane & the cytoplasm of the dead keratinocytes that comprise of stratum corneum.^19,20

Figure 2: Skin Penetration Pathways for the Delivery of Nanoparticles

Transappendegeal pathway:

The transappendegeal pathway delivers the drugs through skin due to intercellular route. In this route drugs are easily crossing the skin from its small sized molecules. This route making the delivery of drugs more twisted.²¹Stratum corneum thickness is about 20µm and the real penetration way of some molecules to cross the skin is about 400µm. The Transappendegeal pathway enhances the delivery of drugs through hair follicles, and it is also known as transfollicular route.²²

Types of Skin Cancer:

There are many triggers to develop skin cancer, but the primary risk factor for the development of skin cancer is exposure and damage of our skin through harmful UV-radiation, natural and the solar radiation both will harm to skin.^23,24,25 Some other triggers like genetic predisposition, imbalance in immune system by attacking to viral infections and some harmful chemicals eg: aromatic hydrocarbons, arsenic etc. These are some important factors & also potential risks for developing skin cancers.^26,27 Cancer is classified into two categories one is known as melanoma skin cancer (MSC) and the second type is known as non-melanoma skin cancer (NMSC).

In the cancer disease the Basal Cell Carcinomas (BCCs) were common type of malignant cancer. They develop by basal cells and the basal cells are present in the epidermis and located in the in the head & face of epidermis. The occurrence of BCC has been increased upto 33% over the past two decades.^28,29 Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. It occurs by increase in the proliferation of malignant cells in the epidermis, and they can invade the dermis layer. When proliferation is occurred in tumour then the disease is named as SCC Bowen’s disease. A precancerous situation of cSCC, actinic keratosis (AK), is caused by chronic exposure of epidermis to harmful ultraviolet (UV) radiations, x-irradiation, or some polycyclic aromatic hydrocarbons. Clinically, actinic keratosis develops the scales of flesh colored, and erythematous papule or plaques are also formed in the range of 1-2mm. The features on skin are advance into squamous cell carcinoma (SCC) in situ or into its invasive form.^30,31

Clinical management of skin cancers:

For the early cureness of skin cancer it is important to provide the suitable diagnosis and treatment to the patient. Surgical & non-surgical actions are helpful in the treatment of cancer features.^32,33 A physician may first diagnose the patient by his/her history of disease, reoccurrence, type of medication, skin thickness, plaques and the genetic history of a person. Patient first choice is the important parameter in the treatment of cancer disease in terms with regard convenience, tolerability and the cost of treatment.³⁴ Some the surgical procedures are given as:

· Cryosurgery

· Laser therapy

· Curettage

· Desiccation

· Dermabrasion

· Radiation therapy

· Moh’s micrographic surgery

These are the effective tool for cancer treatment furthermore, they will cause some complications to the patient pain, serious disfigurement, edema, gastrointestinal hemorrhage, secondary infection, chronic ulcer formation, blister formation, hypo-pigmentation, scarring, hair loss, and radio dermatitis with non healing ulcerations among, etc.^35,36

When the lesions covered the whole body of a person then large treatment process is required generally non-surgical procedures are useful for patients who are not candidates for surgery. In such type of cases, field aimed therapies can get rid of clinically visible & subclinical features & prevents them.³⁷ The proper use of radiation therapy, photodynamic therapy, and topical chemotherapeutic or immune-modulator drugs were helpful. These are used as single or sometime they are used in combination with other therapy or procedures.³⁸The topical agents which are used as single or in addition with other therapy (Photodynamic therapy) are given as:

· Aminolevulinic acid (ALA)

· Methyl aminolevulinate (MAL)

These agents have great potential to kill the tumor. Topical therapies are primarily used when there are multiple lesions are developed or the area of treatment is large.³⁹ More time is required to heal such type of lesions. Topical therapies are generally given to those patients who are no able to take surgical treatments. However, the rates of curing the skin cancer through topical agents were not more effective than surgical treatments.⁴⁰

Topical therapies are delivered through skin & they reach the systemic circulation by crossing the skin layers.^41.42 There are some commonly used topical agent which includes some corticosteroids is given as:

· 5-fluorouracil (5-FU, Efudex)

· Imiquimod

· Resiquimod

· Ingenol

· Mebutate

· Diclofenac

· Retinoids

· Mechlorethamine

· Carmustine

· Bexarotene

· Tazarotene

· photodynamic

Nanoparticles based technology for Dermal Delivery:

Over the years, Nanoparticles based systems have been widely researched and they are experiment in vitro & in vivo by topical delivery through skin. To underst& the use of Nanoparticles they have been good potential to cross the skin layers and effective penetration of drugs (bioactive molecules) in tumor site. This will increase the retention of drug in the skin & tumor. The fewer doses are required, and the chances of toxicity are also minimum, or it can improve the patient compliance.⁴³ Nanoparticles based topical therapies are yet to be approved in a commercial context. Here, we highlight various systems evaluated for the topical therapy of skin cancers & aim to underst& the parameters that possibly govern the engineering of an ideal topical formulation. Several Nanoparticles technologies have been designed, engineered, and evaluated for applications in dermatology.⁴⁴ Here, we provide a brief overview of some of the most commonly tested systems in topical delivery Figure 3.

Figure 3: Nanoparticles Technologies for Dermal Delivery

Vesicular carriers:

Liposomes:

Liposomes are mainly composed of cholesterol and phospholipids and they are ensuing in hydrophobic entities with an aqueous core for the solubility of hydrophilic drugs.⁴⁵ Liposomes have great potential to improve the pharmacokinetics of drugs, specificity, and to increase the efficacy of drugs with decrease in their toxicity. Liposomes are established to get drug retention in skin layers. Liposomes with 50 nm particle size have been easily penetrated through the surface of skin.⁴⁶

Niosomes:

Niosomes are similar with liposomes & they are made by the use of nonionic surfactants, nonionic surfactants. Niosomes are highly stable, less expensive or very economical to produce than liposomes.⁴⁷ Niosomes can alter the subcutaneous barrier by fusing with the lipids. The particles of Niosomes can also boost the smooth nature of subcutaneous layer & by the recovery of lost lipids it can reduce the transepidermal water loss.⁴⁸

Transferosomes:

Accordingly, the use for topical or transdermal drug delivery system is some degree of extent. This lead to high efficiency vesicles called as Transferosomes, they are invented by Cevc and Blume in 1992.⁴⁹ Transferosomes contains an aqueous core bounded by a phospholipids bilayer and an edge activator.⁵⁰ This promotes an enhanced SC penetration of Transferosomes via the intercellular route to deliver drugs deep inside the skin.

Ethosomes:

Ethosomes are elastic vesicles and they composed of phospholipids, cholesterol, water, and large amounts of ethanol.⁵¹ They are first introduced by Touitou et al, the ethosomes are elastic on nature and the elasticity of ethosomes is mainly due to the effect of cholesterol and ethanol on the phase transition temperature of phosphatidylcholine.⁵² Ethosomes delivers the drug deeper in skin layer and the drug reaches systemic circulation easily. Ethosomes were highly stable and they get greater antifungal activity with controlled-release attributes in the clinical studies.⁵³

Transethosomes:

Transethosomes firstly introduced by Song CK et al, these are the lipid vesicles and they are made with the combination and features of Transfersomes and Ethosomes.⁵⁴ In Transethosomes approximately 30% ethanol was present along with edge activators. The edge activators increase the penetration of Transethosomes through skin layers. Transethosomes was designed for their better penetration through skin & they were effective in the chemotherapeutic treatment of many skin diseases⁵⁵.

Lipid Nanoparticles:

Lipid Nanoparticles is the best approach for the topical delivery of drugs. Due to high stability & good tolerability they were extensively used. Lipid Nanoparticles protect the drugs from degradation and should maintain a stable release for unlimited periods of time.⁵⁶ Basically two approached are in used with lipid Nanoparticles one is Solid Lipid Nanoparticles (SLNs) & second is Nanostructured Lipid Carriers (NLC). Both the nanocarriers were effective against skin diseases.⁵⁷

Solid Lipid Nanoparticles (SLN):

Solid lipid Nanoparticles (SLNs) are colloidal systems & the particle size were in the range of 50nm to 1000 nm.⁵⁸ Solid lipid Nanoparticles (SLNs) are made-up from a mixture of biodegradable and biocompatible solid lipids molecules. Emulsifiers and water were used to produce SLNs via a high pressure homogenization method. Commonly used lipids are triglycerides, glycerides, fatty acids, and waxes.⁵⁹ The ability of SLNs is merging with insoluble drugs with lipid matrix. Some studies prove the capability of SLNs to diminish edema and deliver mRNA, and antifungal medications such as terbinafine, econazole nitrate, miconazole nitrate and itraconazole. Due to their deeper penetration capacity they will increase the retention & sustained release of drugs through skin.⁶⁰

Nanostructured Lipid Carriers (NLCs):

Nanostructured Lipid Carriers (NLCs) are made-up from solid and liquid lipids in combination & they do not acquire the perfect crystalline structure of molecules. The lipid is both enclosed within the solid lipid matrix & located in the surfactant layer.⁶¹ The liquid phase in the NLCs decreases in the water content and they can also provide high drug loading. These particles are commonly used for the attributes for controlled drug release.⁶² In the previous studies NLCs will improve the efficacy and delivery of drug through topical route, which can significantly improved the bioavailability of drugs & penetrate in the deeper side of skin. They will also boost the anti-inflammatory response of drugs at a reduced dose with no irritation at site of drug delivery.⁶³

Polymeric Micelles & Nanoparticles:

Polymer Micelles and Nanoparticles were self made with hydrophobic core & hydrophilic shell. The inner core of the micelles were used to make a increase the bioavailability of poorly soluble drugs & the outer core were used to get the desired solubility when in contact with aquas surroundings.⁶⁴ Normally, the particle size of polymeric micelles ranges from 10-80nm for drug delivery through topical route. Micelles can be manufactured to improve the specificity and efficacy of these compounds which includes antibodies, peptides, aptamers, carbohydrates, and small molecules etc. The copolymers were usually blocked and they can release the drug in reaction to chemical and physical cues like pH, thermo, ultrasound, or light etc. The main function of the Polymeric Nanoparticles is to penetrate the drugs through skin via a follicular pathway i.e. retaining inside the hair follicles.⁶⁵

Natural Polymeric Nanoparticle:

Natural polymers were formed with Chitosan NPs have been studied extensively for dermal drug delivery.⁶⁶ Chitosan (N-deacetylated) is a derivative of chitin which is biodegradable and cationic in nature. The positive charge of Nanoparticles will enhance the particles to come in contact with negative charge on the surface of skin, which leads to change in the barrier and delivery of drugs through skin.⁶⁷

Synthetic Polymeric Nanoparticle:

For the preparation of synthetic polymeric Nanoparticles, the biodegradable polymers (lactide-co-glycolide), copolymers (PLGA), polylactic acid (PLA), and poly (ε-caprolactone) have been reported for topical delivery of drugs. Sun et al established an effective treatment of curcumin loaded PLGA with particle size in the range of 50-150nm. The hydrogel formulation of curcumin was compared with imiquimod (IMQ) induced psoriasis like mouse model.⁶⁸ Because of their small size they have capability to make depots by retaining with hair follicles on the surface of skin. These polymers may built-in with paramagnetic metals which includes gadolinium (Gd) or manganese (Mn), as image contrast agents for topical diagnosis.

Dendrimers:

Dendrimers are prepared from synthetic polymers commonly they are called as mono dispersed Nanoparticles. The particles are settled down at the centre which gives them symmetry to arrange in to repeating units and that may results to form a layered architecture. Dendrimers commonly used in drug delivery of Poly-amidoamines, poly (L-lysine), scaffold Dendrimers, polyesters and poly-propylimines.⁶⁹ When compared with neutral or anionic Dendrimers, the cationic Dendrimers can alter skin permeability by interacting with its lipids. Cationic Dendrimers have been evaluated as permeation enhancers following skin pretreatment or co-administration with drugs.⁷⁰

Nanogels and ‘PEG’-NPs:

Dendrimers are made up of dendritic polyglycerol (dPG) have been used to form hydrophilic & thermo receptive 3D-crosslinked nanogels. Nanogels formulations will enhance the penetration of small or large size drug particles across the skin layer and they also have ability to retain with hair follicles.⁷¹ These nanogels have ability to increase the dermal penetration and also increased in the ionic strength, temperature, or skin pH.⁷²

Nanoemulsions:

Nanoemulsions thermodynamic stable dispersions of oil in water (o/w) or water in oil (w/o) and they are stabilized by an interfacial film of surfactant molecules.⁷³ The mean diameter of Nanoemulsions droplets were range from 20 to 200nm with low percentage of surfactant. These properties of Nanoemulsions were responsible for the effective topical drug delivery of drugs with decrease in skin irritation.⁷⁴ Nanoemulsions are soluble with lipophilic drugs and the large surface area of Nanoemulsions was responsible to create a close occlusive contact with the stratum corneum and gradually increase the penetration of drugs deeper inside the skin. The permeability of drugs will increase by adding oils & surfactants in Nanoemulsions.⁷⁵

Nanofibers:

Electrospun Nanofibers have shown great potential in topical drug delivery, especially as meshes for wound healing and antimicrobial activity. Nanofibers are different from Nanoparticles and they were designed with less than 100nm size of particles, which easily carrying both the hydrophilic or hydrophobic drugs.⁷⁶ Nanofibers have been evaluated extensively as systems for dermal drug delivery. These technologies were used to deliver the drugs in a controlled manner.⁷⁷

Metallic Nanoparticles

Metallic Nanoparticles were made up of gold, silver, and metallic oxides. Nowadays metallic Nanoparticles have been widely used in the formulation of skin products. Drugs are built-in with the core or they are bound to the surface of metallic nanoparticles. The various metallic oxides were used for the preparation of metallic nanoparticles eg; iron, titanium, zinc etc. They are available and studied for the delivery of active drugs through dermal route. The particles present in the metallic nanoparticles were accumulated on the surface, & they do not cause any epidermal toxicity.^78,79

Design and Characteristics of Nanoparticles:

Design of Nanoparticles:

For the development of nanoparticles it is important to follow the required steps for designing nanoparticles and their target. For the delivery of nanoparticles the following routes of administration eg; topical, transdermal, intratumoral or systemic are helpful. All these routed have several biological barriers & character. That’s why, it is important to underst and the therapeutic targeting of tissue and the required delivery of drugs. For the treatment of skin cancers there is great need to optimize the design of nanoparticles.⁸⁰ For the topical delivery of drugs there are two main things to be considered one is known as permeation by SC layer & second is the accumulation of drugs in epidermis. The small particle will definitely penetrate the skin through intercellular pathway via lipid matrix. On the other h&, hydrophilic drug with large molecular size, which includes peptides, and nucleic acids, for those drugs the topical delivery were not easy.⁸¹ The well design of nanoparticles will improve the solubility of drugs for highly hydrophobic drugs.

Particle size features of Nanoparticles:

Particles size of nanoparticles promotes the penetration of drug through dermal route. Nanoparticles are penetrated well via the skin, & will increase the bio-distribution of drugs. The size of nanoparticles makes effect on pharmacokinetics & bio-distribution with the cellular uptake, and safety of drugs. Nanoparticles with particle size ranging from 6 to 30nm were easily capable to penetrate the skin through intracellular and intercellular routes. The systemic application of nanoparticles with ≤30nm particle size was quickly cleared from body via renal excretion. Particles with size between 200 to 300nm, were retained mostly in the spleen and liver and ≤400nm size particles were quickly cleared via hepatic clearance.⁸²

Shape features of Nanoparticles:

The intonation in the shape of nanoparticles will absolutely plays an important role to increase the penetration of drugs via dermal route. Nanoparticles with ideal size properties were increase the subcellular targeting. The rod-shaped, spherical & triangular shape nanoparticles were studied for their capability to penetrate different layers of skin. in comparison between all these shaped the triangular nanoparticles were found to be less penetration via the skin & they were penetrate the drug more slowly as compare to rod shaped & spherical shaped nanoparticles. In addition, the rod shape nanoparticles accumulate the drug in higher levels in the dermal layer, which increase their systemic effects.⁸³

Treatment of skin cancer by Nanoparticles drug delivery:

Chemotherapies:

The drugs which are used in chemotherapy of skin cancers include Dacarbazine, Temozolomide, Nitrosoureas, Vinca alkaloids, Taxanes, and cisplatin has been frequently used for the treatment of MSC [84]. Another drug called as 5-FU is vigorously and extensively used for the treatment of skin cancers conditions like actinic keratosis & basal cell carcinomas.⁸⁵ On the On the other hand, 5-FU is very much hydrophilic in nature and it is capable to achieve the target by reaching to tumor tissues though the subcutaneous layer.

Dacarbazine were used in the treatment of skin cancer treatment and it has a short half-life and is a poorly soluble active drug. Dacarbazine is used as a single for the treatment of skin cancer and it was approved by FDA for their anticancer property. The choice of Dacarbazine in (MSC) melanoma skin cancer chemotherapy was effective.⁸⁶ Dacarbazine is encapsulated in lipid nanoparticles for topical delivery in melanoma skin cancer (MSC) treatment.

Carboplatin were also used and it is a class of second generation drug with platinum compound and it can also suggested by the food & drug association (FDA) for the treatment of melanoma skin cancer. Carboplatin was loaded into poly (ε-caprolactone) nanoparticles with a chitosan-β-glycerophosphate gel via intratumoral administration.⁸⁷ As well as, the antitumor effect of Carboplatin was discovered during in vitro and in vivo study by Su et al. (2017), who manufactured the paclitaxel-loaded copolymer nanoparticles.⁸⁸

Temozolomide, Nitrosoureas, Vinca alkaloids, Taxanes and cisplatin has also been used for the treatment of melanoma skin cancer (MSC). Temozolomide were prepared in the form of solid lipid nanoparticles, and they were used in the delivery of Temozolomide In other hand the Temozolomide were also be delivered through polyamide-amine dendrimer (PAMAM) for targeting the human melanoma cells by in vitro.⁸⁹

Immunotherapy and therapeutic vaccines:

The immune system is of supreme term for cancer development. In an unbeaten antitumor response the antigens linked with tumor (TAAs) are obtainable by antigen presenting cells (APCs) to T cells, which include dendritic cells (DCs). The T cells are activated when the receptors were engaged with peptides and major histocompatibility complex (MHC) molecules. Afterward, these effectors cells travel via tumor & they will lead to penetrate the tumor tissue.⁹⁰ The whole process will lead to generate the cells which are responsible for the development of skin cancer. To overcome such type of obstacles first line immune therapy plan were used for the treatment of melanoma skin cancer (MSC) was the use of cytokines, which resulted to enhance the overall patient survival. This plan was successfully gain good sides with their aim to promote the growth and immune cells activity. Due to the short half life of cytokines a high dose was needed for the application process. The high dose in administration causes several unnecessary side effects to the patients.⁹¹

Cancer vaccines are designed to be potential mechanisms that generate a long-lasting response to cancer development by stimulating immune memory of TAAs. Cancer vaccination with nucleic acids can be DNA-based or RNA-based. For this strategy to be effective, them RNA or DNA must be taken up by the APCs and translated to induce antigen expression. Although nucleic acid vaccination has shown interesting results in melanoma animal models, clinical trials showed no significant clinical outcomes, often because of barriers to nuclear delivery and immunogenicity.⁹² Vaccination with TAA peptides is another exciting strategy for antitumor treatment.

Gene therapy:

The approach of gene therapy was planned in 1966 & to compile this approach nucleic acids were used to restore or return a faulty or absent gene. The treatment of cancer by gene therapy can be applied by three dissimilar classes of genetic material which includes plasmid DNA (pDNA), RNA interference (RNAi), and antisense oligo nucleotides (AONs). These approaches will enable the blow in or giveaway of a targeted gene depending upone the targeted material from above categories.⁹³ Nanoparticles have also been industrialized to get better in the delivery of genetic material & transfection by local application. Furthermore, the RNA interference (RNAi) molecules in multifaceted with liposomes were applicated intra-tumorally to promote the effective therapy for the treatment of melanoma skin cancer (MSC).⁹⁴

Nanocarriers combined with physical methods:

For the effective therapy in cancer treatment the physical techniques were used. These methods were probably increasing the topical delivery of drugs. They have been practically applied in the clinic since the 1980s and now they emerged as potential approaches for the treatment of skin cancers. The modification for nanoparticles was based on the electrical, mechanical, or material structures or velocity. These approaches were generally used in combination or linked with varieties of nanoparticles to improve the permeation mechanism and distribution of drugs via dermal delivery.^95,96 The various physical methods for the treatment of melanoma skin cancer (MSC) and non melanoma skin cancer (NMSC) tabulated in Table 1.

Laser irradiation therapy:

In the laser therapy technique a Photodynamic therapy (PDT) has been extensively used and it is very useful therapeutic approach. A photodynamic therapy in combination with particular light wavelength took an advantage to decrease the production of singlet oxygen molecules which are highly reactive. They cause cell death in a series of biological, chemical & physiological reactions.^97,98

Table 1: Nanocarriers combined with a physical method for skin cancer therapy.

Physical Method	Nanocarriers	Anti-Cancer agent	Reference
Laser irradiation – PDT	Mesoporous silica NPs PEGylated gold NPs Cubic liquid-crystalline Nanodispersions Solid lipid NP Transethosomes Polymersomes	Vertoporphyrin Mitoxantrone Chlorin-e6 or meso-tetraphenylporphine-Mn III) chloride Aluminum chloride Ferrous chlorophyllin Protophorphyrin IX	97
Laser irradiation – PAT	Light-responsive nanocapsules	Doxorubicin Doxorubicin	98
Laser irradiation – PTT	PEGylated carbon nanotubes PEGylated gold NPs Gold NP coated-liposome Gold NP coated-liposome	Curcumin Curcumin Cantharidin	98
Iontophoresis	Polymers-coated gold NPs	Imatinib mesylate & STAT-3 siRNA	99
Microneedle	PEGylated gold nanorod and micelles Gold nanocage Liposome pH-responsive lipid NPs	Docetaxel Doxorubicin Doxorubicin & celecoxib Cisplatin	100
Ultrasound	Polymeric NPs Nanocapsule nanoconjugate & Microbublee Liposome Nanoemulsions	Docetaxel & chlorine 6 Curcumin & topotecan STAT-3 siRNA & curcumin Zinc phthalocyanine	101

CONCLUSION:

Now a days Nanotechnology is a science, which had established & being used effectively for the treatment of various diseases along with challenges. Nanomedicine for dermal carcinoma has already become a recent systematic exercise, and it has revealed in modern time a key progress in the management of skin cancer, including various types of other carcinoma. Nanoparticles are effectively being used by carry active molecules or their combination for the tumor treatment. The special therapies & individual therapies have been possible with the use of nanoparticles which leads to lower side effects related with person to person variability.

In conclusion, Nanoparticles along with various therapies like Chemotherapies, Immunotherapy, Gene therapy, Nano carriers combined with physical methods and Laser irradiation used in more efficient ways, which should be useful in the treatment of skin cancer & also help in the reduction in cost of cancer treatment. In last we can say that nanotechnology offers several techniques against dermal carcinoma or treatment of skin cancer, still there is a need of more and effective strategy for the management of cancer which should be safe and 100 percent effective.

ACKNOWLEDGEMENT:

We acknowledge the resources & support for the study was provided by the Department of Pharmaceutics, Laureate Institute of Pharmacy, Kathog Himachal Pradesh, INDIA. .

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 23.09.2020 Modified on 01.11.2020

Research J. Pharm. and Tech 2021; 14(10):5589-5598.

DOI: 10.52711/0974-360X.2021.00973