Tackling the various classes of nano-therapeutics employed in topical therapy of psoriasis

Figures & data

Figure 1. Psoriatic plaques covered with silvery scales compared to normal skin parts.

Figure 2. A summary of the underlying pathogenesis of psoriatic skin lesions.

Figure 3. Various types of nanocarriers used for topical drug delivery.

Table 1. A summary of polymers that are commonly used for nano drug delivery targets.

Polymer	Characteristics	Application
PLGA	One of the first and most commonly used polymers in drug delivery First used in the mid 1980s FDA approved Biocompatible Biodegradable	Used for many drug delivery applications including: vaccination, cancer (Danhier et al., 2012)
PEG	A hydrophilic polymer Generally safe First used in the late 1960s	Used as a coating material for nanoparticles to achieve more efficient drug delivery by extending the drug’s circulation time in the bloodstream; to avoid elimination by RES "stealthing" (Suk et al., 2016)
Poloxamer/ PEO-PPO-PEO	A block co-polymer Amphiphilic nature Its molecular weight can be customized according to application Can arrange in solution to form polymeric micelles	Widely used for drug delivery and medical imaging Application and characteristics differ according to molecular weight ((Moghimi and Hunter, 2000)
Polyplexes:	A combination of a cationic polymer and nucleic acid therapeutics PEI: A cationic polymer, accused of high toxicity Protamine: A natural polypeptide; composed of cationic arginine units Safer than PEI but less efficient FDA approved	Used as non-viral vectors for gene delivery (Tros de Ilarduya et al., 2010)
Chitosan	A natural hydrophilic cationic polysacccahride FDA approved Biocompatible Biodegradable Derived from crustacean shells	Used extensively for drug delivery Chitosan nanoparticles are positively charged and mucoadhesive and achieve sustained drug release ((Mohammed et al., 2017)
SF	Natural biopolymer Biodegradable Biocompatible Minor immunogenicity	Nanoparticles can be synthesized from this polymer by various methods for treatment of cancer and other diseases (Gianak et al., 2018)
Albumin	Natural biopolymer Hydrophilic Mostly suitable for hydrophilic drugs	Used extensively in drug delivery and medical imaging; there are many marketed formulations for treatment of cancer, diabetes, multiple sclerosis and other conditions (An and Zhang, 2017)
Gelatin	Natural biopolymer Hydrophilic Mostly suitable for hydrophilic drugs	Used for drug and gene delivery for conditions such as; cancer, tuberculosis and human immunodeficiency viral infection (Yasmin et al., 2016)
Dextran	Natural biopolymer Hydrophilic Mostly suitable for hydrophilic drugs	Often used with functionalization for specific targeting, for example, the CNS or liver cells (Foerster et al., 2016; Ibegbu, 2015; Liu et al., 2018)
PLA-PCL-PGA	Forms polymeric micelles Biodegradable Synthetic PLA is hydrophilic PCL is Hydrophobic PGA is Hydrophilic	PGA, PLA and PCL and their copolymers are the most commonly used materials for nanoparticles synthesis for the purpose of drug delivery (Hans and Lowman, 2002)
PAMAM/PPI	Used as a dendritic platform PPI is the first-discovered dendrimer	Used to incorporate hydrophobic drugs in particular, as they improve their solubility and control their release (Huang and Wu, 2018)
PHPMA	A non-biodegradable synthetic polymer	Synthesis of new drug delivery systems with tailored characteristics (Huang and Wu, 2018)
PACA	Synthesized by anionic polymerization Biodegradable Biocompatible FDA approved	Used alone or with a copolymer for the purpose of drug delivery for cancer or other diseases. Widely used for delivery of different therapeutic agents in different forms of nanocarriers including: nanocapsules, nanospheres, long circulating nanoparticles and nanoparticles conjugated with targeting moieties (Yordanov, 2012)

PLGA: polylactic co-glycolic acid; PEG: polyethylene glycol; PEO-PPO-PEO: polyethylene oxide-polypropylene oxide-polyethylene oxide; PEI: polyethyleneimine; SF: silk fibroin; PLA-PCL-PGA: polylactic acid-polycaprolactone-polyglycolic acid; PAMAM: polyamidoamine; PPI: polypropyleneimine; PHPMA: polyhydroxylpropylmethacrylamide; PACA: polyalkylcyanoacrylates.

Table 2. A summary of recent approaches carried out to formulate drug delivery systems for topical management of psoriasis using polymeric nanoparticles.

Drug	Drug delivery system	Method of preparation	Findings
Tretinoin	Lipid-core PCL nanocapsules	Interfacial deposition	Decreased skin permeation and photodegradation (Ourique, 2011)
	PCL lipid-core nanocapsules	Interfacial deposition	Enhanced antiproliferative activity (a significant decrease in the mitotic index) (FACHINETTO et al., 2008)
Tacrolimus	Chitosan-Nicotinamide nanoparticles Hyaluraunic acid-cholesterol-nicotinamide nanocarriers	Ionic gelation Ultrasonic cell disruption of a nicotinamide solution of tacrolimus and hyalauronic-acid cholesterol conjugate	Better drug solubility, EE and stabilityEnhanced permeability (Yu et al., 2017) Improved solubility and facilitated drug loading, Enhanced skin permeation (Gabriel et al., 2016; Wan et al., 2017)
	mPEG-hexPLA nanoparticles	Emulsion solvent diffusion method	Higher drug loading, Better accumulation in the SC (Gabriel et al., 2016)
Curcumin	PLGA nanoparticles	Anti-solvent and flash precipitation	Accumulation in the SC and sustained release (Sun et al., 2017)
	RRR-α-tocopheryl succinate-grafted-ε-polylysine conjugate	Dialysis-homogenization	Sustained release and enhanced efficacy by an occlusive effect through skin hydration (Mao et al., 2017)
Nile red as a model for lipophilic compounds	Core multishell dendritic carriers	Modified film uptake	A promising biocompatible carrier for antipsoriasis agents (Pischon et al., 2017)
Clobeatsol propionate	Lecithin-chitosan nanoparticles	Direct injection of soybean lecithin ethanolic solution into chitosan solution	Better skin accumulation, Low transdermal delivery (Şenyiğit et al., 2010)
	PLGA microparticulates	Emulsion solvent evaporation	Improved in vitro antipsoriatic activity (Badıllı et al., 2011)
	PCL lipid-core nanocapsules	Interfacial deposition	Improved anti-inflammatory efficacy (Fontana et al., 2011)
Cyclosporin A	Micellar nanocarriers	Solvent evaporation method	Better SC deposition and solubility (Lapteva et al., 2014)
	PLGA nanoparticles	Modified emulsion-diffusion-evaporation Method	Better percutaneous delivery Minimized transdermal side effects (Jain et al., 2011)
Methotrexate	PolyNIPAM-co-BA Nanogel	Surfactant-free emulsion polymerization	PH-responsive formula Better skin accumulation with a minimum lag time Minimized transdermal side effects (Singka et al., 2010)
Hydrocortisone	PCL nanoparticles	Modified solvent displacement method	Good polymer biocompatibility (Rosado et al., 2013)

EE: entrapment efficiency; SC: stratum corneum; PolyNIPAM-co-BA: poly N-isopropylacrylamide co-butylaccrylate.

Table 3. Recent approaches utilizing metallic nanoparticles in management of chronic psoriasis.

Metallic nanoparticle	P.S range	Active ingredient	Method of preparation	Conclusion
Gold	13–52 nm	Corneal cherry (Cornus mas)extract	Green synthesis	Nanoparticles specifically target macrophages in psoriatic skin plaques (Crisan et al., 2018). No significant cytotoxic effects on culture cell lines.
	2–24 nm			TNF-α decreased production and IL-6 increased production in culture cell line (Perde-Schrepler et al., 2016)  Lower cytotoxicity than chemically synthesized citrate-coated gold nanoparticles.
	10–15 nm	Short interfering RNAs	Chemical synthesis	Efficient suppression of gene expression and T cell production (Nemati et al., 2017). No toxicity on skin cells.
	4–5 nm	Methotrexate	Chemical synthesis	Efficient cell growth inhibition when compared to drug alone and deeper skin penetration. No reported toxicity on skin cells (Bessar et al., 2016).
	11–90 nm	A natural extract of berries; cyaniding 3-O-glucoside and cyaniding 3-O-sambuboside	Green synthesis	Anti-inflammatory effect of cyaniding 3-O-sambuboside > cyaniding 3-O-glucoside > hydrocortisone (Crisan et al., 2013) Immunohistological examination showed no cytotoxicity both in vitro and in vivo.
Silver	9–82 nm	Corneal cherry (Cornus mas)extract	Green synthesis	Nanoparticles specifically target macrophages in psoriatic skin plaques (Crisan et al., 2018). No significant cytotoxic effects on culture cell lines.
	20–80 nm	A natural extract of berries rich in polyphenols and anthocyanins	Green synthesis	Proved to decrease cytokine production both in vitro and in vivo (David et al., 2014). Better anti-inflammatory effect than hydrocortisone. Cytotoxicity reported.
Platinum	1.7–3.1 nm	No added therapeutic agent	Chemical synthesis	Inhibition of a major signaling pathway of inflammation (Rehman et al., 2012)  No vital cytotoxic effects reported.

Table 4. A summary of lipidic nanosystems for topical treatment of psoriasis in the past few years.

Delivery system	Production technique	Drug	Findings
Particulate systems
SLNs	Modified emulsification and low temperature solidification method	Tacrolimus	Higher skin penetration and retention than marketed ointment (Ruihua, 2012).
	Thin film hydration	Erlotinib + IL α 36SiRNA	Decreased epidermal hyperplasia (Boakye et al., 2017). Decreased infiltration of inflammatory cytokines.
	Hot ultrasonication	Methotrexate + Etanercept	Decreased transdermal permeation (Ferreira et al., 2017).
	Solvent injection	Mometasone Furoate	Higher skin deposition than commercial cream (Madan et al., 2014).
	Solvent injection	Betamethasone 17-valerate	Controlled release (Zhang and Smith, 2011). Drug retention in epidermis.
	Pre-emulsion ultrasonication	Dithranol	Double drug localization than the commercial cream (Zhang and Smith, 2011).
NLCs	Hot emulsion sonication	Thymol	Improved healing of psoriatic plaques in mouse models (Pivetta et al., 2018).
	Microemulsion	Mometasone Furoate	Disappearance of parakeratosis^a (Kaur, Sharma and Bedi, 2018). Increased skin deposition 2.5 times than marketed product.
	High-shear homogenization	Methotrexate	Enhanced skin penetration (Pinto et al., 2014).
	Microemulsion technique	Clobetasol propionate	Increased drug accumulation in the stratum corneum (Silva et al., 2012).
	Hot homogenization	Tacrolimus	Higher penetration than commercial product (Nam et al., 2011).
	Thin film hydration	Calcipotriol + Methotrexate	Suppressed skin permeation of calcipotriol only (Fang, 2010). Lower skin irritation.
	A modified microemulsion technique	Fluticasone propionate	Improved drug encapsulation and formulation physicochemical stability (Doktorovová et al., 2010).
A comparative study between SLNs and NLCs	Hot melt homogenization method	Cyclosporin & calcipotriol	Both particulate systems show deeper penetration (Arora et al., 2017). NLCs exhibited higher efficacy than SLNs and commercial gel.
	Solvent diffusion technique	Capsaicin	Both particulate systems minimize skin irritation (Agrawal et al., 2015). NLCs show better stratum corneum permeation and retention than both SLNs and plain drug.
	Microemulsification	Tretinoin	Higher efficacy and biocompatibility than the commercial product containing Tretinoin (Raza et al., 2013). Particulate lipidic systems show higher photostability and skin permeation than vesicular systems.
Lipospheres	Modified emulsion-based method	Thymoquinone	Improved histopathological and psoriatic features of psoriatic skin both in vivo and in vitro (Jain et al., 2017). Decreased TNF-α, IL-2, IL-6 and IL-1β.
	Modified emulsion-based method	Tacrolimus + curcumin	Improved histopathological and psoriatic features of psoriatic skin in vivo (Jain et al., 2016). Decreased TNF-α, IL-17,IL-22.
Liquid crystals	Lipid melting, mixing with the aqueous phase and sonication	siRNAs	Gene downregulation GAPDH suppression (Vicentini et al., 2013).
		siRNAs	Reduction of IL-1α and IL-6 production (Depieri et al., 2016).
Vesicular systems
Liposomes	Thin film hydration	Fusidic acid	A more stable formulation with a higher efficacy (Wadhwa et al., 2016).
	Thin film hydration	Tretinoin	Particulate lipidic systems show higher photostability and skin permeation than vesicular systems (Raza et al., 2013).
	Thin film hydration	Calcipotriol	A smaller particles size (<100 nm) and a unilamellar structure which promoted skin penetration and drug deposition (Knudsen et al., 2012).
	Thin film hydration	Methotrexate	Increased skin permeability (Srisuk et al., 2012).
	Thin film hydration	Tretinoin	Higher skin deposition (Manconi et al., 2011).
Niosomes	Thin film hydration	Anthocyanins	Prolonged antiinfalmmatory effect with no cytotoxicity (Manconi et al., 2011).
Ethosomes	Modified injection method	Psoralen	Improved permeation and skin deposition (Zhang et al., 2014).
	The cold method	Tretinoin	Particulate lipidic systems show higher photostability and skin permeation than vesicular systems (Zhang et al., 2014).
	Thin film hydration	5-aminolevulinic acid	Enhanced accumulation in both normal and hyperproliferative skin (Fang et al., 2009). Higher penetration depth Reduced TNF-α expression
A comparative study between liposomes and niosomes	Thin film hydration	Dithranol	Both vesicles showed better skin permeation both in vitro and in vivo (Agarwal et al., 2001).
A comparative study between emulsomes, liposomes and niosomes	Thin film hydration	Capsaicin	Emulsomes showed to be a convenient carrier achieving higher penetration and retention (R. Gupta et al., 2016).
SECosomes^b	Solvent evaporation method	RNAi	Downregulation of the psoriatic genetic marker (human beta-defensin 2) (Desmet et al., 2016).
Emulsion systems
Microemulsion	Titration	Protopanaxdiol	Higher in vivo and in vitro skin deposition (Kim et al., 2018).
	Titration	Methotrexate	Increased epidermal drug accumulation with lower systemic absorption, that is, improved efficacy and safety (Amarji et al., 2016).
	Aqueous phase titration	Betamethasone dipropionate + salicylic acid	Improved and sustained anti-inflammatory activity and higher skin penetration (Baboota et al., 2011).
	Shaking mixtures of the components of the microemulsion with the calculated ratios	Tacrolimus	Superior bioavailability (Baboota et al., 2011).
Nanoemulsion	High shear homogenization	Cyclosporin	Increased drug permeability in vitro and superior skin hydration on human volunteers (Musa et al., 2017).
	Spontaneous emulsification	Clobitasol propionate + calcipotriol	Better uptake by stratum coreum in vitro (Kaur et al., 2017). Better antipsoriatic skin activity in vivo.

^aA type of cell keratinization where the nuclei are retained in the stratum corneum. ^bA liposomal carrier developed by the authors.

Table 5. A summary of vesicular lipid drug delivery systems that have been invented by formulators in the past years.

Vesicular system	Definition
Liposomes	Natural or synthetic bilayer/s of phospholipids and cholesterol as a fluidity modifier (Bansal et al., 2012; Jain et al., 2014).
Niosomes	One or more bilayers consisting of amphiphilic nonionic surfactants instead of phospholipids (Bansal et al., 2012; Jain et al., 2014).
Trasferosomes	Flexible and deformable liposomes (Bansal et al., 2012; Jain et al., 2014).
Aquasomes	A solid ceramic core with a carbohydrate coat (Jain et al., 2014).
Colloidosomes	Spherical structures with a hollow core and a coat of particles that are formed by coagulation at the interface of emulsion droplets (Jain et al., 2014).
Cubosomes	Cubic shaped vesicles (Jain et al., 2014).
Sphingosomes	Liposomes formed of sphingolipids instead of phospholipids (Jain et al., 2014).
Ufasomes	Unsaturated fatty acids forming bilayered structure that attach to the surface of the skin (Patel et al., 2011).
Cryptosmes	Vesicular structures with a coat of phosphatidyl choline and phosphatidyl ethanolamine (U. et al., 2019).
Discomes	Disc-shaped structures similar to niosomes (Uchegbu et al., 1992).
Emulsomes	Drug nano-carriers with a solid lipid core and a phospholipid bilayer surface (Zhou and Chen, 2015).
Enzymosomes	Liposomes with a functional group of one or more enzyme (S. et al., 2017).
Genosomes	Vesicles that consists of genetic material and positively charged lipids (Tadwee et al., 2011).
Ethosomes	Liposomes that contain: ethanol, water and a penetration enhancer (Tadwee et al., 2011).
Photosomes	A liposome that incorporates photolysase enzyme (Tadwee et al., 2011).
Virosomes	Phospholipid vesicles with virus-extracted proteins (Tadwee et al., 2011).
Vesosomes	Multivesicular structures synthesized using ethanol and certain types of phospholipids (Tadwee et al., 2011).
Proteasomes	Lipid vesicles with protease enzymes (Tanaka, 2009).
Herbosomes	Liposome-like structures incorporating phytochemicals (Anwana, 2015).
Layerosomes	Phospholipid bilayer vesicles with a surface of polyelectrolytes (Agnihotri et al., 2004).
Pharmacosomes	Very fine particles consisting of covalently linked drug and lipids (Bansal et al., 2012).

Danhier F, Ansorena E, Silva JM, et al. (2012). PLGA-based nanoparticles: an overview of biomedical applications. Drug Deliv Res Eur 161:505–22.

 Google Scholar

Suk JS, Xu Q, Kim N, et al. (2016). PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 99:28–51.

 PubMed Web of Science ®Google Scholar

Moghimi SM, Hunter AC. (2000). Poloxamers and poloxamines in nanoparticle engineering and experimental medicine. Trends Biotechnol 18:412–20.

 PubMed Web of Science ®Google Scholar

Tros de Ilarduya C, Sun Y, Düzgüneş N. (2010). Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci 40:159–70.

 PubMed Web of Science ®Google Scholar

Mohammed MA, Syeda JTM, Wasan KM, Wasan EK. (2017). An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics 9:53.

 PubMed Web of Science ®Google Scholar

Gianak O, Kyzas G, Samanidou V, Deliyanni E. (2018). A review for the synthesis of silk fibroin nanoparticles with different techniques and their ability to be used for drug delivery. 14:339–48.

 Google Scholar

An F-F, Zhang X-H. (2017). Strategies for preparing albumin-based nanoparticles for multifunctional bioimaging and drug delivery. Theranostics 7:3667–89.

 PubMed Web of Science ®Google Scholar

Yasmin R, Shah M, Khan SA, et al. (2016). Gelatin nanoparticles: a potential candidate for medical applications. Nanotechnol Rev 6:191.

 Web of Science ®Google Scholar

Foerster F, Bamberger D, Schupp J, et al. (2016). Dextran-based therapeutic nanoparticles for hepatic drug delivery. Nanomed 11:2663–77.

 PubMed Web of Science ®Google Scholar

Ibegbu MD. (2015). Functionalised dextran nanoparticles for drug delivery to the brain. J Nanomed Nanotechnol 6:95.

 Google Scholar

Liu W, Quan P, Li Q, et al. (2018). Dextran-based biodegradable nanoparticles: an alternative and convenient strategy for treatment of traumatic spinal cord injury. Int J Nanomed 13:4121–32.

 PubMed Web of Science ®Google Scholar

Hans ML, Lowman AM. (2002). Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–27.

 Web of Science ®Google Scholar

Huang D, Wu D. (2018). Biodegradable dendrimers for drug delivery. Mater Sci Eng C 90:713–27.

 PubMed Web of Science ®Google Scholar

Yordanov G, (2012). Poly(alkyl cyanoacrylate) nanoparticles as drug carriers 33 years later. Bulg J Chem 1:61–73.

 Google Scholar

Ourique AF, Melero A, Bona da Silva C. et al. (2011). Improved photostability and reduced skin permeation of tretinoin: development of a semisolid nanomedicine. Eur J Pharm Biopharm 79:95–101.

 PubMed Web of Science ®Google Scholar

Fachinetto JM, Ourique AF, Lubini G, et al. (2008). Tretinoin-loaded polymeric nanocapsules: evaluation of the potential to improve the antiproliferative activities on allium cepa root-tip compared to the free drug. Lat Am J Pharm 27:668–73.

 Web of Science ®Google Scholar

Yu K, Wang Y, Wan T, et al. (2017). Tacrolimus nanoparticles based on chitosan combined with nicotinamide: enhancing percutaneous delivery and treatment efficacy for atopic dermatitis and reducing dose. Int J Nanomed 13:129–42.

 PubMed Web of Science ®Google Scholar

Gabriel D, Mugnier T, Courthion H, et al. (2016). Improved topical delivery of tacrolimus: a novel composite hydrogel formulation for the treatment of psoriasis. J Contr Rel 242:16–24.

 PubMed Web of Science ®Google Scholar

Wan T, Pan J, Long Y, et al. (2017a). Dual roles of TPGS based microemulsion for tacrolimus: enhancing the percutaneous delivery and anti-psoriatic efficacy. Int J Pharm 528:511–23.

 PubMed Web of Science ®Google Scholar

Sun L, Liu Z, Wang L, et al. (2017). Enhanced topical penetration, system exposure and anti-psoriasis activity of two particle-sized, curcumin-loaded PLGA nanoparticles in hydrogel. J Contr Rel 254:44–54.

 PubMed Web of Science ®Google Scholar

Mao K-L, Fan Z-L, Yuan J-D, et al. (2017). Skin-penetrating polymeric nanoparticles incorporated in silk fibroin hydrogel for topical delivery of curcumin to improve its therapeutic effect on psoriasis mouse model. Coll Surf B Biointerfaces 160:704–14.

 PubMed Web of Science ®Google Scholar

Pischon H, Radbruch M, Ostrowski A, et al. (2017). Stratum corneum targeting by dendritic core-multishell-nanocarriers in a mouse model of psoriasis. Nanomed Nanotechnol Biol Med 13:317–27.

 PubMed Web of Science ®Google Scholar

Şenyiğit T, Sonvico F, Barbieri S, et al. (2010). Lecithin/chitosan nanoparticles of clobetasol-17-propionate capable of accumulation in pig skin. J Contr Rel 142:368–73.

 PubMed Web of Science ®Google Scholar

Badıllı U, Şen T, Tarımcı N. (2011). Microparticulate based topical delivery system of clobetasol propionate. AAPS PharmSciTech 12:949–57.

 PubMed Web of Science ®Google Scholar

Fontana MC, Rezer JFP, Coradini K, et al. (2011). Improved efficacy in the treatment of contact dermatitis in rats by a dermatological nanomedicine containing clobetasol propionate. Eur J Pharm Biopharm 79:241–9.

 PubMed Web of Science ®Google Scholar

Lapteva M, Santer V, Mondon K, et al. (2014). Targeted cutaneous delivery of ciclosporin A using micellar nanocarriers and the possible role of inter-cluster regions as molecular transport pathways. J Contr Rel 196:9–18.

 PubMed Web of Science ®Google Scholar

Jain S, Mittal A, K. Jain A. (2011). Enhanced topical delivery of cyclosporin-A using PLGA nanoparticles as carrier. Curr Nanosci 7:524–30.

 Web of Science ®Google Scholar

Singka GSL, Samah NA, Zulfakar MH, et al. (2010). Enhanced topical delivery and anti-inflammatory activity of methotrexate from an activated nanogel. Eur J Pharm Biopharm 76:275–81.

 PubMed Web of Science ®Google Scholar

Rosado C, Silva C, Reis CP. (2013). Hydrocortisone-loaded poly(ε-caprolactone) nanoparticles for atopic dermatitis treatment. Pharm Dev Technol 18:710–8.

 PubMed Web of Science ®Google Scholar

Crisan D, Scharffetter-Kochanek K, Crisan M, et al. (2018). Topical silver and gold nanoparticles complexed with Cornus mas suppress inflammation in human psoriasis plaques by inhibiting NF-κB activity. Exp Dermatol 27:1166–9.

 PubMed Web of Science ®Google Scholar

Perde-Schrepler M, David L, Olenic L, et al. (2016). Gold nanoparticles synthesized with a polyphenols-rich extract from cornelian cherry (Cornus mas) fruits: effects on human skin cells. J Nanomater 2016:1–13.

 Web of Science ®Google Scholar

Nemati H, Ghahramani M-H, Faridi-Majidi R, et al. (2017). Using siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation in psoriasis. J Contr Rel 268:259–68.

 PubMed Web of Science ®Google Scholar

Bessar H, Venditti I, Benassi L, et al. (2016). Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis. Coll Surf B Biointerfaces 141:141–7.

 PubMed Web of Science ®Google Scholar

Crisan M, David L, Moldovan B, et al. (2013). New nanomaterials for the improvement of psoriatic lesions. J Mater Chem B 1:3152.

 PubMed Web of Science ®Google Scholar

David L, Moldovan B, Vulcu A, et al. (2014). Green synthesis, characterization and anti-inflammatory activity of silver nanoparticles using European black elderberry fruits extract. Coll Surf B Biointerfaces 122:767–77.

 PubMed Web of Science ®Google Scholar

Rehman MU, Yoshihisa Y, Miyamoto Y, Shimizu T. (2012). The anti-inflammatory effects of platinum nanoparticles on the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages. Inflamm Res 61:1177–85.

 PubMed Web of Science ®Google Scholar

Ruihua W. (2012). FK506-loaded solid lipid nanoparticles: preparation, characterization and in vitro transdermal drug delivery. Afr J Pharm Pharmacol 6: 904–13.

 Google Scholar

Boakye CHA, Patel K, Doddapaneni R, et al. (2017). Novel amphiphilic lipid augments the co-delivery of erlotinib and IL36 siRNA into the skin for psoriasis treatment. J Controlled Release 246:120–32.

 PubMed Web of Science ®Google Scholar

Ferreira M, Barreiros L, Segundo MA, et al. (2017). Topical co-delivery of methotrexate and etanercept using lipid nanoparticles: a targeted approach for psoriasis management. Coll Surf B Biointerfaces 159:23–9.

 PubMed Web of Science ®Google Scholar

Madan J, Dua K, Khude P. (2014). Development and evaluation of solid lipid nanoparticles of mometasone furoate for topical delivery. Int J Pharma Investig 4:60.

 PubMedGoogle Scholar

Zhang J, Smith E. (2011). Percutaneous permeation of betamethasone 17-valerate incorporated in lipid nanoparticles. J Pharm Sci 100:896–903.

 PubMed Web of Science ®Google Scholar

Pivetta TP, Simões S, Araújo MM, et al. (2018). Development of nanoparticles from natural lipids for topical delivery of thymol: investigation of its anti-inflammatory properties. Coll Surf B Biointerfaces 164:281–90.

 PubMed Web of Science ®Google Scholar

Kaur N, Sharma K, Bedi N. (2018). Topical nanostructured lipid carrier based hydrogel of mometasone furoate for the treatment of psoriasis. Pharma Nanotechnol 6:133–43.

 PubMedGoogle Scholar

Pinto MF, Moura CC, Nunes C, et al. (2014). New topical formulation for psoriasis: development of methotrexate-loaded nanostructured lipid carriers. Int J Pharm 477:519–26.

 PubMed Web of Science ®Google Scholar

Silva LAD, Taveira SF, Lima EM, Marreto RN. (2012). In vitro skin penetration of clobetasol from lipid nanoparticles: drug extraction and quantitation in different skin layers. Braz J Pharm Sci 48:811–7.

 Web of Science ®Google Scholar

Nam S-H, Ji XY, Park J-S. (2011). Investigation of tacrolimus loaded nanostructured lipid carriers for topical drug delivery. Bull Korean Chem Soc 32:956–60.

 Web of Science ®Google Scholar

Fang J-Y, Lin Y-K, Huang Z-R. (2010). Combination of calcipotriol and methotrexate in nanostructured lipid carriers for topical delivery. Int J Nanomed 5:117–28.

 PubMed Web of Science ®Google Scholar

Doktorovová S, Araújo J, Garcia ML, et al. (2010). Formulating fluticasone propionate in novel PEG-containing nanostructured lipid carriers (PEG-NLC). Coll Surf B Biointerf 75:538–42.

 PubMed Web of Science ®Google Scholar

Arora R, Katiyar SS, Kushwah V, Jain S. (2017). lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics in treatment of psoriasis: a comparative study. Expert Opin Drug Deliv 14:165–77.

 PubMed Web of Science ®Google Scholar

Agrawal U, Gupta M, Vyas SP. (2015). Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of psoriasis. Artif Cells Nanomedicine Biotechnol 43:33–9.

 PubMed Web of Science ®Google Scholar

Raza K, Singh B, Lohan S, et al. (2013). Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity. Int J Pharm 456:65–72.

 PubMed Web of Science ®Google Scholar

Jain A, Pooladanda V, Bulbake U, et al. (2017). Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis. Nanomed Nanotechnol Biol Med 13:2251–62.

 PubMed Web of Science ®Google Scholar

Jain A, Doppalapudi S, Domb AJ, Khan W. (2016). Tacrolimus and curcumin co-loaded liposphere gel: synergistic combination towards management of psoriasis. J Contr Rel 243:132–45.

 PubMed Web of Science ®Google Scholar

Vicentini FTMC, Depieri LV, Polizello ACM, et al. (2013). Liquid crystalline phase nanodispersions enable skin delivery of siRNA. Eur J Pharm Biopharm 83:16–24.

 PubMed Web of Science ®Google Scholar

Depieri LV, Borgheti-Cardoso LN, Campos PM, et al. (2016). RNAi mediated IL-6 in vitro knockdown in psoriasis skin model with topical siRNA delivery system based on liquid crystalline phase. Eur J Pharm Biopharm 105:50–8.

 PubMed Web of Science ®Google Scholar

Wadhwa S, Singh B, Sharma G, et al. (2016). Liposomal fusidic acid as a potential delivery system: a new paradigm in the treatment of chronic plaque psoriasis. Drug Deliv 23:1204–13.

 PubMed Web of Science ®Google Scholar

Knudsen NØ, Rønholt S, Salte RD, et al. (2012). Calcipotriol delivery into the skin with PEGylated liposomes. Eur J Pharm Biopharm 81:532–9.

 PubMed Web of Science ®Google Scholar

Srisuk P, Thongnopnua P, Raktanonchai U, Kanokpanont S. (2012 May). Physico-chemical characteristics of methotrexate-entrapped oleic acid-containing deformable liposomes for in vitro transepidermal delivery targeting psoriasis treatment. Int J Pharm 427:426–34.

 PubMed Web of Science ®Google Scholar

Manconi M, Sinico C, Caddeo C, et al. (2011). Penetration enhancer containing vesicles as carriers for dermal delivery of tretinoin. Int J Pharm 412:37–46.

 PubMed Web of Science ®Google Scholar

Zhang Y-T, Feng N-P, Shen L-N, Zhao J-H. (2014). Evaluation of psoralen ethosomes for topical delivery in rats by using in vivo microdialysis. Int J Nanomedicine 9:669–678.

 PubMed Web of Science ®Google Scholar

Fang Y-P, Huang Y-B, Wu P-C, Tsai Y-H. (2009). Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior. Eur J Pharm Biopharm 73:391–8.

 PubMed Web of Science ®Google Scholar

Agarwal R, Katare OP, Vyas SP. (2001). Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int J Pharm 228:43–52.

 PubMed Web of Science ®Google Scholar

Desmet E, Bracke S, Forier K, et al. (2016). An elastic liposomal formulation for RNAi-based topical treatment of skin disorders: proof-of-concept in the treatment of psoriasis. Int J Pharm 500:268–74.

 PubMed Web of Science ®Google Scholar

Kim K-T, Kim M-H, Park J-H, et al. (2018). Microemulsion-based hydrogels for enhancing epidermal/dermal deposition of topically administered 20(S)-protopanaxadiol: in vitro and in vivo evaluation studies. J Ginseng Res 42:512–23.

 PubMed Web of Science ®Google Scholar

Amarji B, Garg NK, Singh B, Katare OP. (2016). Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics. J Drug Target 24:147–60.

 PubMed Web of Science ®Google Scholar

Baboota S, Sharma S, Kumar A, et al. (2011). Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis. Int J Pharma Investig 1:139.

 PubMedGoogle Scholar

Musa SH, Basri M, Fard Masoumi HR, et al. (2017). Enhancement of physicochemical properties of nanocolloidal carrier loaded with cyclosporine for topical treatment of psoriasis: in vitro diffusion and in vivo hydrating action. Int J Nanomed 12:2427–41.

 PubMed Web of Science ®Google Scholar

Kaur A, Katiyar SS, Kushwah V, Jain S. (2017). Nanoemulsion loaded gel for topical co-delivery of clobitasol propionate and calcipotriol in psoriasis. Nanomed Nanotechnol Biol Med 13:1473–82.

 PubMed Web of Science ®Google Scholar

Bansal S, Kashyap CP, Aggarwal G, Harikumar S. (2012). A comparative review on vesicular drug delivery system and stability issues. 10:704–13.

 Google Scholar

Jain S, Jain V, Mahajan SC. (2014). Lipid based vesicular drug delivery systems. Adv Pharm 2014:1–12.

 Google Scholar

Patel DM, Patel C, Jani R. (2011). Ufasomes: a vesicular drug delivery. Syst Rev Pharm 2:72.

 Google Scholar

Uchegbu IF, Bouwstra JA, Florence AT. (1992). Large disk-shaped structures (discomes) in nonionic surfactant vesicle to micelle transitions. J Phys Chem 96:10548–53.

 Web of Science ®Google Scholar

Zhou X, Chen Z. (2015). Preparation and performance evaluation of emulsomes as a drug delivery system for silybin. Arch Pharm Res 38:2193–200.

 PubMed Web of Science ®Google Scholar

Tadwee IK, Gore S, Giradkar P. (2011). Advances in topical drug delivery system: a review. International Journal of Pharmaceutical Research and Allied Sciences 1:14–23.

 Google Scholar

Tanaka K. (2009). The proteasome: overview of structure and functions. Proc Jpn Acad, Ser B 85:12–36.

 PubMed Web of Science ®Google Scholar

Anwana U. (2015). Herbosomes in the delivery of phytotherapeutics and nutraceuticals:concepts,applications and future perspective. Covenant J Phys Life Sci 3:10–22.

 Google Scholar

Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. (2004). Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Contr Rel 100:5–28.

 PubMed Web of Science ®Google Scholar