The concept “novel drug delivery system” (NDDS) refers to an innovative and rational approach based on physical (osmosis, diffusion, swelling, erosion, dissolution, and electron-chain transport) and bio-chemical (monoclonal antibodies, gene therapy, carrier loaded therapy, polymer-drug conjugates, liposome, and noisome) mechanisms that have been developed having optimized properties of drugs such as tunable particle size in micro and nano range, improved permeability parameters and specific site targeting via advancing our understanding of the pharmacokinetic and pharmacodynamic behavior of the drug. NDDS can be obtained via either of three ways the development of nano-carrier loaded, sustain released drug delivery systems, and application of micro-fluidics ^[1][2][3][1,2,3].

Nanoparticles have been revealed to be beneficial in gathering information at all phases of clinical trials due to their application in numerous innovative tests for the treatment and diagnosis of diseases. The advantageous characteristic of the nanoparticle is to allow multiple proteins to attach to their surface over conventional dosage forms [4].

In 2008, Alexander and Serguei first coined the phrase “nano-particle constructed gel” to describe cross-linked bi-functional scaffolds of a swellable non-ionic polymer and a polyion for delivery of polynucleotides. Extremely cross-linked, three-dimensional nano-ranged hydrogel systems that can be either co-polymerized or made of ionic or non-ionic monomers are known as nano-gels having a size range of 20–200 nm, offering several beneficial effects such as having prolonged serum half-life, absorbing large amounts of body fluids without altering the fundamental networked structure and avoiding renal clearance ^[5][6][5,6]. The desire for nano-gels as a delivery system is fueled by their well-known excellent properties, including higher thermodynamic stability, remarkable solubilization potential, comparatively lower viscosity, and resistance to aggressive sterilization procedures [7]. Nano-gels, a dual combination of hydrogels and nanoparticles, have demonstrated significant promise as a targeted drug delivery system in the treatment of cancer, attributing to excellent drug loading capacity. Other advantages of nano-gel over other nanoparticles are to achieve active targeting via making a response to internal or external stimuli such as pH, temperature, light, and reduction-oxidation reaction with improved drug deposition in a targeted area, minimizing adverse effects of a drug via preventing drug accumulation in non-targeted tissues [8]. Nano-gels can be differentiated into different categories such as physically-chemically cross-linked, hybrid nano-gel, polymeric, bio-mimetic nano-gel, pH, thermo, magnetic, hypoxia, ultrasound, enzyme, and reduction responsive nano-gel on the basis of synthesis procedure, nature of materials used and responsive towards stimuli respectively ^[8][9][8,9]. The swellable property of nano-gel makes them able to expand when in contact with physiological fluids providing flexibility to be near the targeted region drugs under particular physiological circumstances and increasing the dispersion of medicaments [10]. Nano-gels can be either synthetically modified to incorporate numerous ligands for targeted drug delivery or controlled drug release or primarily a transporter architecture for delivering pharmaceuticals and several bio-active compounds such as genes, proteins, etc. ^[11][12][13][11,12,13]. Depending on the type and properties of both drug and nano-gel being utilized as well as desired release pattern, there are many techniques to load drugs into them, such as physical entrapment (mixture of drug and nano-gel solution adsorb onto the surface or be encapsulated within the nano-gel matrix through physical entrapment), chemical conjugation (chemical reaction of drug molecules to nano-gel surface via covalent bonding), electrostatic interaction (electrostatic attraction between drug molecule and charged nano-gel surface) and stimuli (pH, temperature, and pressure) sensitive loading. However, the restriction in the entrapment of hydrophobic medications such as anticancer drugs in hydrophilic nano-gels can be overcome via modifying polymer structure, resulting in improved solubility and stability of poorly soluble drugs significantly [14]. Therefore, nano-gels are thought to be potential drug delivery carriers for the delivery and cellular uptake of proteins, peptides, and other biological compounds, attributing to relatively high affinity to aqueous solutions, remarkable thermal stability, bio-compatibility, fully or partially bio-degradability and suitability for molecular inclusion in bulk ^[15][16][17][15,16,17].

Skin disorders, the 4th foremost source of non-fatal diseases, are frequently the outward manifestation of more serious systemic illnesses, such as HIV, and neglected tropical diseases, such as elephantiasis and other ailments causing lymphedema [18]. Over a million cases of skin inflammation and cancer are discovered each year, making it by far the most prevalent form of cancer in people, especially in white people ^[19][20][21][19,20,21]. Skin malignancies are given names based on the cell from which they develop and their clinical characteristics. The three most frequent forms are cutaneous malignant melanoma, basal cell carcinomas, and squamous cell carcinomas. Basal cell carcinomas and squamous cell carcinomas are both also known as non-melanocytic skin cancers ^[19][22][19,22]. Similar to many other malignancies, Melanoma, the most combative skin cancer, greatly rises with age, likely due to the lengthy latency between carcinogen exposure and the development of cancer. In this case, UV exposure was a contributing factor ^[19][23][19,23]. In order to implement a coordinated and long-lasting global response to lowering the global burden, it is essential to comprehend the impact of dermatological disorders in wealthy countries around the world. Chemotherapeutic drugs cannot be used topically due to the physiological structure of the skin, poor affinity, and potency, whereas the drug-loaded targeted nano-gel formulations were found to be released more in slightly acidic melanoma micro-environment compared with other topical conventional formulations [24]. Therefore, nano-gels establish innovative architecture having improved pharmacological potential and maintained intracellular safety limits for the mitigation and treatment of targeted melanoma.