Caffeine-loaded niosomes for cellulite therapy were developed and tested. Compared to the market-available product Cellu Destock®, a histology study revealed that the gel contained niosomes was significantly decreased the size and thickness of the fatty tissue of the skin in rats. Furthermore, the niosomal group had a greater caffeine penetration, showing that the niosomes containing caffeine increased the drug permeation through the skin and the deep fatty layer. This is a possible technique for developing a caffeine-based topical anti-cellulite drug as niosomes with enhanced topical administration [
1]. Vitamin C, commonly known as ascorbic acid, is an antioxidant found in many cosmetics and beauty items. Due to the very low stability of ascorbic acid in cosmetic products, the stabilised ascorbic acid derivative, magnesium ascorbyl phosphate (MAP), was created as vesicular carriers: ethosomes and niosomes. Because of their low hydrophilic–lipophilic balances (HLBs) (about 4.7 and 4.3, respectively), span60 and span80 were chosen as nonionic surfactants for the synthesis of niosomes. Nonionic surfactants with high HLB values inhibit bilayer formation, whereas span60 and span80 promote the development of sturdy, stiff, and undamaged niosomes with high entrapment efficiency. Formulations containing span60 had a much higher encapsulation efficiency than those containing span80 at the same surfactant and cholesterol ratio. Span80 has a lower ability to create tighter, less porous niosomes than span60, leading to leaky rigid bilayers with bigger particle sizes and lower encapsulation effectiveness. The adjusted niosomes formulation has a higher entrapment efficiency at 86.82 ± 4.52% compared to ethosomal formulation of 83.43 ± 2.23%. While much less MAP was absorbed into the skin after 8 h in both the ethosomal and niosomal gels than in their respective formulations, this allowed for regulated and efficient drug administration throughout the skin layers. After clinical testing of the MAP ethosomal and niosomal gels for the treatment of melasma, the authors proposed combining the two formulations to potentially provide faster and longer-lasting outcomes. The ethosomes responded more quickly and the niosomes had a longer-lasting impact [
41]. Garca-Manrique et al. (2016) used a full factorial design to examine how the modified ether injection method’s experimental parameters affected the mean size and distribution of sizes of the fabricated liposomes and niosome particles. With the model equations discovered, more stable liposomes and niosome particles of the desired sizes were synthesised effectively, with encapsulation efficiencies for certain hydrophobic substances exceeding 73.9% in all cases (Sudan Red 7B and vitamin D3). The most important variables found by ANOVA were the organic/aqueous phase volume ratio, (final aqueous-phase) phospholipid content, and sonication amplitude. These findings provide fresh understanding of the operation and outcomes of the variables involved in the EIM’s creation of niosomes. Meanwhile, these specialised soft niosomes might be used for diagnostic or therapeutic purposes in the food, cosmetic, pharmaceutical, or medical industries [
42]. Because of its widespread usage as a food ingredient, supercritical carbon dioxide (scCO2) was employed as the solvent (scRPE technique) to create niosomes with polyglycerol fatty acid ester (PG ester)-type. These surfactants are generated from natural sources and are not damaging to the human body or the environment. Organic solvents must be avoided in cosmetics because customers prefer cosmetics created from safer components, particularly organic ingredients. The scRPE method was used to create niosomes with ethanolic co-solvent. Decaglycerol distearate (DG2S) and decaglycerol diisostearate (DG2IS) were used in this process to create niosomes. Decaglycerol tristearate (DG3S), which has a low HLB number, created a gel-like mixture, while decaglycerol monostearate (DG1S), which has a high HLB number, formed a solution of spherical particles. Because of the increased membrane fluidity of DG2IS niosomes, they exhibit better trapping efficiency and dispersion stabilities than DG2S niosomes. The molecule’s branching hydrophobic components cause this membrane fluidity. The results of this study provide important knowledge about the environmentally acceptable way for producing niosomes utilising nonionic surfactants produced from natural sources for cosmetic and medicinal uses [
43]. The development of niosomes to improve skin irritation behaviour and bioavailability of tazarotene resulted in prolonged drug penetration across the skin and enhances drug retention within the skin compared to plain drug gel and tazarotene-marketed formulation [
11].Acitretin niosomes developed by thin-film hydration using span60 and cholesterol produced an entrapment efficiency of 90.3%. When the formulated niosomes were dispersed in hydroxypropyl methylcellulose gel matrix to produce niosome-based gel, it showed an enhanced ex vivo permeation profile up to 30 h and significant drug deposition in the viable epidermal–dermal layers compared to free acitretin gel with higher in vivo anti-psoriatic activity, negligible skin irritation, and better skin tolerability [
11]. Azelaic acid (AA) has been shown to possess antimicrobial and anti-cancer activities. The hydrophilicity and lipophilicity of AA can be modified to AA β-cyclodextrin complex (AACD) and diethyl azelate (DA), respectively [
21]. AA, AACD, and DA were entrapped in liposomes and niosomes by the chloroform film method with sonication. These encapsulated systems showed nanosize characteristics with good physical stability. The authors also concluded that AA and its derivatives were safe for topical use for pharmaceutical and cosmetic applications when entrapped in nanovesicles because of no toxicity to normal cell lines and no allergy on rabbit skin [
44]. Bromelain is widely used in a variety of fields, including medicine, health, food, and cosmetics, due to its powerful proteolytic action [
45]. Novel elastic vesicles have been developed to deeply and easily penetrate through the skin; among them, elastic niosomes are the most recent novel elastic nanovesicles which have been developed [
1,
31,
45]. This newly designed elastic niosomal formulation was employed to include protease enzymes (papain and bromelain), with the goal of treating keloids and hypertrophic scars. Blank and enzyme-loaded elastic niosomes are smaller than non-elastic niosomes. Bromelain-loaded niosomes have lower particle sizes than control particles, which was ascribed to charge interaction between bromelain and the vesicular membrane [
45]. KT2 and RT2 are antimicrobial peptides, from crocodile (Crocodylus siamensis) leukocyte. KT2 and RT2 provide strong efficacy to kill both Gram-positive bacteria and Gram-negative bacteria, besides preventing biofilm formation. Niosomes are encapsulated with KT2 and RT2 for better stability. KT2 and RT2 were successfully encapsulated in the niosomes with corresponding encapsulation rates of 70.4% and 59.6%, respectively. Peptides’ varying niosome encapsulation efficacy might account for differences in how well they dissolve in PBS. Lysine (K) and arginine (R), two distinct types of basic amino acids that are present in KT2 and RT2, respectively, may be a critical factor in peptide solubility. The uncoated niosomes were then coated with hydroxypropyl methylcellulose phthalate (HPMCP), resulting in larger sizes. The peptide-encapsulated niosomes possess a high-enough electrostatic stability, and following coating with HPMCP, their electrostatics may be enhanced. This property of niosomes is significant for long-term preservation and usage, particularly in cosmetic and aesthetic product formulation and medicinal drug delivery [
46]. Vitamin B12 niosomes were developed and characterised because of their synergistic effect with antibiotics. The produced vitamin B12 niosomal formulations could be useful in the food, cosmetics, and pharmaceutical industries, according to the author [
47]. Formulation development and evaluation for catechins tea nanoparticles such as niosomes were reported due to their application in cosmetics. The low bioavailability and poor skin penetration of catechins, which may be improved by the formulation of nanotechnology, were the second key driver behind the invention of catechins tea niosomal particles [
48]. Different types of essential oils, including tea tree, lavender, sandalwood, rosemary, bergamot, rose, chamomile, ylang-ylang, jasmine, lemon, orange, basil, eucalyptus, turmeric, lemongrass, peppermint, patchouli, frankincense, citronella, cinnamon, geranium, and cedarwood, were used to prepare niosomes and other types of nanoparticles to improve skin conditions [
49]. A catalytic application of niosomes was reported when the thin film hydration method was used to prepare copper niosomes made from span20, span40, span80, and cholesterol in the mixture of chloroform and methanol as the mixture solvent. The study showed a promised catalytic activity of the prepared niosomes [
50]. As a result of their tiny size and rapid penetration, cosmeceutical niosomes have been used to treat skin diseases, including herpes labialis, when formed into a lipstick, lip balm, and lip rouge containing acyclovir using the thin film hydration technique [
51] All lipstick, lip balm, and lip rouge niosomes containing acyclovir were prepared using span60, span80, and cholesterol in different ratios. According to the findings of an experiment that compared lipstick, lip balm, and lip rouge for in vitro release, lip rouge was shown to be the most effective formulation in terms of physicochemical qualities and drug release. It will have a favourable aesthetic application as well as an increased therapeutic impact in the management of recurrent herpes labialis since it is a cosmetic formulation with an appealing appearance, colour, and flavour [
51]. These findings could be useful for the treatment of skin diseases that fall under the umbrella of niosomes being employed in cosmetic applications. Laslau et al. (2020) found that niosomes containing ascorbic acid had an entrapment efficacy of 30–50%, with span80 formulations outperforming tween80 [
52]. Tween80’s increased hydrophilicity may favour ascorbic acid retention on the vesicle’s surface rather than encapsulation within it, increasing the amount of unencapsulated medication and so reducing the value of entrapment efficiency. Improved skin permeation was seen when the ellagic acid prepared as niosomes contained a mixture of span60 and tween60. The study highlighted the significant effect of particle size of the produced niosomes on the skin rate penetration [
53].
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