Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects

Figures & data

Fig. A1 Schematic representation of various layers of human skin and penetration of UV radiation to the various layers of human skin.

Fig. A2 Effect of UV radiation on human skin.

Fig. A3 Diagrammatic representation of the chemical sunscreen mechanism of action.

Fig. A4 Diagrammatic representation of the physical sunscreen mechanism of action.

Table A1 FDA approved sunscreen agents.

U.V Blockers	Range covered (nm)	Description
Para amino benzoic acid (PABA)	290–340	Effective UV-B filters when used in a 5% concentration in 50–60% alcohol base. It penetrates deep into the dermis, acidic in nature. Current use in sunscreen formulations is limited due to its in vitro carcinogenicity and allergic reactions (contact and photoallergic) [27]
Sulisobenzone(Benzophenone-4)	290–340	It is a broad spectrum sunscreen agent approved by the FDA in a concentration of 5%. Highly stable and strong oxidizing agent. Sulisobenzone is water insoluble in its acid form [27]
3-Benzylidene camphor	290–320	3-Benzylidene camphor is used as a sunscreen agent at levels up to 2%; highly stable. The dermal absorption of the 3-Benzylidene camphor is very low. It is a potential endocrine disruptor and also shows multiple hormonal activities. Soluble in absolute alcohol and isopropanol. Insoluble in water [27]
Bemotrizinol(BEMT)	290–340	Bemotrizinol absorbs ultraviolet radiations in both UV-A and UV-B range. It is oil soluble chemical. Highly photostable. Its presence in formulation also protects less photostable UV blockers, such as avobenzone [27]
Butyl Methoxydibenzoylmethane (Avobenzone)	340–400	Highly effective for UV-A radiations. It is used in combination with other sunscreen agents to cover a broad spectrum of UV radiation. Concentrations up to 3% is used as an effective sunscreen agent. Insoluble in water, soluble in ethanol [27]
Camphor benzalkonium methosulphate	290–340	Camphor benzalkonium methosulphate is used as UV-filter at a maximum concentration of 6.0%. Mild irritating potential to the eye when used undiluted or as a 20% aqueous solution. It has a borderline margin of safety [27]
Diethylamino hydroxybenzoyl hexyl benzoate	340–400	An effective UV-A filter; oil-soluble yellow liquid. Widely used as sun protective agent at concentrations up to 10%. It has good compatibility with other UV filters and other ingredients. High Photostability [27]
Diethylhexyl Butamido Triazone	340–400	In European country, it is used as a UV filter in cosmetics and personal care products at a maximum concentration of 10%. Although FDA approved up to 3 percent only. At 3% concentration, it is efficient and is not irritant as well as non sensitizer, photosensitizer or photoirritant [27]
Drometriazole trisiloxane (silatriazole; Mexoryl XL)	290–340	Photostable broad spectrum UV filter. An allergic reaction is rarely seen [27]
Cinoxate	290–320	A light yellowish liquid, insoluble in water, but soluble in glycerol and various vegetable oil. Covers the spectrum of UV-B [23]
Dioxybenzone	290–340	Broad spectrum UV Blocker from the family of benzophenone used in various other cosmetic formulations, but it is reported as sensitizing agent [23]
Ecamsule (Mexoryl SX)	340–400	Photostable. Has a good safety profile as compared to other UV-A blockers. It is not absorbed by the skin and effectively covers the entire spectrum of UV-A [23]
Homomenthyl salicylate (Homosalate)	290–320	Salycilate derivative, oil soluble. Has a good safety profile, but used in combination with other UV blocker for effective sun blocking activity. Covers, UV-B spectrum. Up to 10% w/w used as a sun screen agent [23]
Meradimate (Menthyl Anthranilate)	340–400	Rarely used anthranilates and it covers only a specific spectrum of UV-A [23]
Octocrylene	290–320	Effective for UV-B range. Photostable, moisturizing effect is observed due to its ethyhexol portion of the molecule. Used in combination with other UV blockers [23]
Ethylhexyl methoxycinnamate and octinoxate	290–320	Used for the protection against UV-B radiation. Water insoluble cinnamate. Used in combination due to its instability [23]
IMC (Amiloxate)	290–320	Insoluble in water, soluble in ethanol and other organic solvents, effective UV-B sunscreen agent, safe [23]
4–4-Methylbenzylidene camphor(enzacamene)	290–320	Ability to protect the skin against UV-B radiation. It also showed estrogenic effect [23]
Methylene-bis-benzotriazolyl tetramethylbutylphenol (Tinasorb M)	290–340	Absorb both UV-A and UB-A radiation It is a new class of UV filters that combine the properties of both UV conventional filters (organic and inorganic) – it scatters, reflects and absorbs UV light. It is colorless organic microfine particles and photostable. Very less systemic absorption [23]
Ethylhexyl Triazone	290–320	Absorb UV light at maximum 5% concentration. Oil-soluble UV-B filter. Insoluble in water, which makes it suitable for water-resistant products. It has excellent photostability[23]
Ethylhexyl salicylate(octylsaliclate; octisalate)	290–320	Octyl salicylate is an oil soluble sunscreen agent, efficient for UV-B radiation. Salicylates are weak UV-B absorbers. Used in combination with other UV filters. Has a good safety profile [23]
Oxybenzone	290–340	Broad spectrum UV filters from the family of benzophenone. Most popular UV blocker. Photostable. Carcinogenic activity is also observed hence its regular use is still argued [28]
Padimate O	290–320	PABA derivative, compatible with various cosmetic ingredients. Used in combination with other UV blocker to attain greater and effective sun blocking agent [28]
Titanium Dioxide	290–340	A physical sunscreen agent. Photostable. Less reactive in nature. Used in micronized and nanosized for their maximum efficacy [28]
Zinc oxide	290–340	Used with titanium dioxide in majority of marketed formulation. zinc oxide is the only sunscreen ingredient that appears on more than one FDA monograph. Microfine zinc oxide effective in the UV-A protection [28]

Fig. A5(a) Imperfect NLCs.

Fig. A5(b) Amorphous NLCs. (c) Multiple NLCs.

Fig. A5(c) Multiple NLCs.

Fig. A6(a) Flow chart of the hot homogenization method.

Fig. A6(b) Flow chart of cold homogenization method.

Table A2 Lipids Used in the NLCs preparation.

	Structure	Description
A. Liquid lipid
Medium Chain Triglyceride/Caprylic Triglyceride		Fatty acid with 6–12 carbon atom and glycerol as backbone. Stable against oxidation, used as solvent, emulsifier and vehicle. These are the lipids with different molecular weight and are easily digestible [84]
Corn Oil		Natural oil and an antioxidant, protects the drug from oxidation due to high unsaturation. Highly viscous [85]
α-Tocopherol		Yellowish viscous liquid, soluble in acetone, ethanol and chloroform. They are unstable in UV light and used as antioxidant and vitamin E supplement [86]
Squalene‘		Translucent liquid. Not used in high concentration. It is a good moisturizer and less susceptible to oxidation. It is an important part of steroid synthesis [87]
Oleic Acid		Yellowish oil, water insoluble. It has low viscosity. On exposure to air it oxidizes. It has been reported to effectively penetrate into the skin and also through hair follicle [88]
B. Solid lipid
Cetyl Palmitate		Ester of palmitic acid. Naturally occurs in the wax found in the skull of sperm whale. Water insoluble, pharmaceutically used for skin conditioning and emollient action. Also used due to its property of excellent film former [89]
Stearic Acid		Saturated fatty acid with 18 carbon backbone. Soluble in acetone and slightly soluble in ethanol. Ability to penetrate skin and even mucous membrane make good candidate for NLC preparations [90]
Tristearin		White, odorless powder, insoluble, emollient in nature, solvent and skin conditioning agent. Controls viscosity of the formulation [91]
Propylene Glycol Monostearate		Soluble in water, colorless liquid. Used as humectants and solvent in various formulations. It is a common ingredient in personal care product [92]
Glyceryl Monostearate		It is glycerol ester of stearic acid. Used as emulsifier as well as thickening agent. It is non-toxic and non-irritant [93]

Table A3 Characterization parameters for NLCs.

S. NO	Parameter	Instrument	Importance
1.	Particle size and charges	Laser Diffractometry	Particle size analysis is important for quality assurance and in consideration of stability aspect [94]
		Photo Correlation spectroscopy (PCS)
		Zetasizer
2.	Particle Morphology	Scanning Electron Microscopy (SEM), Transmission Electron	These high magnification microscopy provides information about surface as well as a three dimensional structure of the nanoparticle. Controlling the morphology of the nanostructure directly affects the properties of the material such as drug loading efficiency, drug release potential etc [95]
		Microscopy (TEM) Atomic Force Microscopy (AFM)
3.	Encapsulation efficiency	Centrifuge	Measurement of the active ingredient encapsulated is necessary to validate the delivery system for being appropriate in carrying the drug to the target site that too in sufficient quantity [96].
		Ultra centrifuge
		HPLC(High Performance Liquid Chromatography)
4	Thermal Analysis	Differential Scanning	Thermal stress leads crystal changes which indirectly affect the particle size and drug loading efficiency, this method also provides information regarding the maximum temperature in which the delivery system is stable and retain to be solid in nature [97]
		Calorimetry
		X-ray Diffraction
5.	Interaction between drug and exipient	Fourier transform infrared (FTIR) spectroscopy	Characteristic peaks of drug give the information of any possible interaction between the drug and excipients in NLCs formulation [98]
6.	Drug release pattern	In-vitro drug release study	Provide the drug release profile from different formulations and help in determining the release of drug from system and its availability [99]
7.	Drug availability in body	In vivo study	Gives the information about the better bioavailibilty of poorly water soluble drugs and proper availability of drugs in different tissues [100]

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