Lipid Nanoparticulate Drug Delivery Systems: Recent Advances in the Treatment of Skin Disorders
Abstract
:1. Introduction
2. Skin
3. Skin Disorders
Treatment of Skin Disorders with Conventional Topical Delivery Systems
4. Lipid-Based Drug Delivery Systems
5. Nanovesicular Carriers
5.1. Emerging Lipid Nanovesicular Carriers
5.2. Nanovesicular Carriers in the Treatment of Skin Disorders
5.2.1. Antipsoriatic Effect
5.2.2. Antifungal Effect
5.2.3. Anti-Vitiligo Effect
5.2.4. Anti-Acne Effect
- The proliferation of propionibacterium acnes bacteria in pilosebaceous units of the skin;
- Local inflammation [135].
5.2.5. Antiviral Effect
5.2.6. Local Anesthetic Effect
5.2.7. Antibiotic Effect
5.2.8. Anticarcinogenic Effect
6. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers
6.1. Solid Lipid Nanoparticles
6.2. Nanostructured Lipid Carriers
6.3. Preparation of SLN and NLC
- Hot homogenization—the lipids are heated above their melting point;
6.4. SLN and NLC in the Treatment of Skin Disorders
6.4.1. Antioxidant Effect
6.4.2. Anti-Inflammatory Effect
6.4.3. Antifungal Effect
6.4.4. Anti-Acne Effect
7. Microemulsions and Nanoemulsions
7.1. Microemulsions
- Oil-in-water (O/W) microemulsion;
- Water-in-oil (W/O) microemulsion;
- Bicontinuous microemulsion [232].
7.2. Nanoemulsions
7.3. Microemulsions and Nanoemulsions in the Treatment of Skin Disorders
7.3.1. Antipsoriatic Effect
7.3.2. Antifungal Effect
7.3.3. Anti-Inflammatory Effect
7.3.4. Antioxidant Effect
7.3.5. Local Anesthetic Effect
7.3.6. Anticarcinogenic Effect
8. Topical Dosage Forms with Lipid Nanoparticulate DDS for the Treatment of Skin Disorders
9. Future Prospects of Lipid Nanoparticulate DDS for the Treatment of Skin Disorders
- Precise delivery across the skin and to certain skin strata, depending on the final target;
- Successful elimination of lipid nanomaterial toxicity threats in topical medical formulations and cosmetics;
- Ensuring improved permeation and low skin irritability as a result of the use of lipid nanocarriers;
- Improved cutaneous release of incorporated API with a broad spectrum of physiological and physicochemical properties.
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug Substance | Main Action | References |
---|---|---|
Corticosteroids | For local application. Manifests a slight immunosuppressive effect. Ineffectiveness in severe cases. | [49] |
Retinoids | Retinoids can be synthetic or natural derivatives of vitamin A. Probable mechanisms of action: Facilitate the transport of cytoplasmic retinoid-binding proteins; influence angiogenesis; modulate T cell responses. | [50,51] |
Vitamin D3 metabolites | Metabolites of vitamin D3 are included in ointments and creams for the treatment of psoriasis. Good effects in milder diseases. Not fully understood effects. The 1,25(OH)2D3 enhances the suppressive activity of CD4(+)CD25(+) cells in draining lymph nodes. | [52,53,54] |
UVB treatment | Multiple effects and effectiveness for several T cell-mediated skin diseases. Not equally effective in the different disorders. Unspecific and generally immunosuppressive. | [55,56,57] |
Methotrexate | Immunosuppressive effect. It does not target specific T cell groups. Still not a fully understood therapeutic effect. | [49,51] |
Cyclosporine A | Affects IL-2 producing cells, in particular CD4(+) T cells. General immunosuppressive effect. | [49,51] |
Lipid-Based Delivery System | Description | Advantages | Disadvantages |
---|---|---|---|
Nanovesicular carriers | |||
Liposomes [68] | Conventional single or multilayer vesicles. Formed by contact of biodegradable lipids with an aqueous medium. Widely used as drug carriers for hydrophilic and lipophilic molecules. | Biocompatible and biodegradable lipids. Conventional production processes. Improved local delivery. Suitable for loading both hydrophobic and hydrophilic substances. | Insufficient chemical and physical stability. Short half-life. Inadequate penetration into the viable epidermis and dermis. High production costs. Difficulties in scalability. |
Transfersomes [69,70,71] | Highly deformable, elastic or ultra-flexible liposomes. Vesicles, similar to conventional liposomes in terms of preparation and structure. Claimed to permeate as intact vesicles through the skin layers. Functionally deformed due to the presence of an edge activator. | Smaller vesicle size, higher elasticity. Compared with conventional liposomes—better penetration through the skin. High membrane hydrophilicity and elasticity allow them to avoid aggregation and fusion under osmotic stress, unlike the conventional liposomes. | Elasticity of these vesicles can be compromised by hydrophobic drug loading. Occlusive application and complete skin hydration limit transdermal delivery due to inhibition of transdermal hydration. Relatively high production costs. Absence of well-established regulatory guidance for skin delivery. |
Ethosomes [72,73] | Lipid vesicles are composed of phospholipids, ethanol, and water. Similar to liposomes in terms of their preparation techniques and structure. Concentration of ethanol 20–45%. Their size decreases with an increase in the ethanol concentration. Exhibit high encapsulation efficiency. | Appropriate for both hydrophobic and hydrophilic drug loading. Enhanced skin delivery under both occlusive and nonocclusive conditions. Higher elasticity, smaller vesicle size, and higher entrapment efficiency than conventional liposomes. | High ethanol content can lead to skin irritation and toxicity. Possible structural and chemical instability during long-term storage. Need to optimize the concentration of lipids and ethanol for improved physicochemical properties and stability of ethosomes. |
Lipid nanoparticulate carriers | |||
Solid lipid nanoparticles [74,75] | Colloidal lipid nanoparticles are composed of a physiological biodegradable solid lipophilic matrix (solid at room temperature and body temperature), in which the drug molecules can be incorporated. | Increased drug stability. High drug payload. Incorporation of lipophilic and hydrophilic drugs. Avoidance of organic solvents. Lack of biotoxicity of the carrier. Relatively cost-effective. | SLN are incorporated into semisolid carriers such as ointments and gels due to the high water content. Potential expulsion of active compounds during storage. Cost-effective manufacturing process. |
Nanostructure Lipid Carriers [76,77] | Colloidal lipid nanoparticles composed of physiological mixing liquid lipid (oils) with the solid lipids, in which the liquid lipid is incorporated into the solid matrix or localized at the surface of solid particles | Improved drug loading compared with SLN. Lower water content compared with SLN. Firmly incorporates the drug substance during storage. Biodegradable and biocompatible. Large-scale production is easily possible. | Tendency to unpredictable gelation. Polymorphic transition. Low drug incorporation due to the crystalline structure of solid lipids. Lack of long-term stability data. |
Lipospheres [78,79,80] | Microspheres, composed of solid hydrophobic lipid core and stabilized by a monolayer of a phospholipid embedded on the surface. | Improved drug stability, especially for photo-labile drugs. Possibility for controlled drug release. Controlled particle size. High drug loading. Biodegradable and biocompatible. | Larger particle size and poor skin permeation compared with lipid-based vesicular carriers, SLN, and NLC. Poor drug loading for hydrophilic compounds. |
Application | Title/Inventors | Year | Results |
---|---|---|---|
CN103006562 (A) | Daptomycin ethosome preparation/ Li Chong, Liu Xia, Yin Qikun, Wang Xiaoying, Chen Zhangbao | 2013 | Stable translucent dispersion system with a small and uniform particle size. High entrapment efficiency. Excellent transdermal performance. Simple and convenient preparation method. |
EP 2810642 A1 | Chitosan-modified ethosome structure/ Chin-Tung Lee, Po-Liang Chen | 2013 | The chitosan-modified ethosome structure contains different active substances. Improved storage and transportation. |
CN103800277 (A) | Leflunomide ethosome composition and its preparation method/ Zhang Tao, Ding Yanji, Deng Jie, Luo Jing, Zhong Xiaodong | 2014 | Improves the transdermal rate of leflunomide. Improves curative effects. |
CN103536700 A | Chinese medicinal ethosome gel patch for treating herpes zoster and preparation method thereof/Bu Ping, Hu Rong, Chen Lin, Wei Rong, Wu Huanhuan, Huang Xiaoli | 2014 | Easy in medication. Convenient to use. Good therapeutic effect. Strong analgesic action. No adverse reaction. |
CN 104706571 A | Preparation method of ethosome/ natural material/polyvinyl alcohol composite hydrogel/Yang Xingxing, Lynn, Chen Mengxia, Fanlin Peng | 2015 | Addition of the polyvinyl alcohol, which improves the properties of the hydrogel. |
CN106474065A | A kind of tetracaine ethosome and its preparation technology/Zhu Xiaoliang, Wu Dongze, Ma Xiaodong | 2017 | Stable in terms of component and proportion. Preferable percutaneous permeation. |
Emerging Lipid Vesicles | Description | Reference |
---|---|---|
Niosomes | Nonionic surfactant and cholesterol (or its derivatives)—based vesicle with improved stability (especially oxidative stability). | [105,106] |
Cubosomes | Submicron, nanostructured particles, composed of bicontinuous cubic liquid crystalline phase. | [107,108,109] |
Hexosomes | Constructed of hexagonal liquid crystalline phases dispersed in a continuous aqueous medium. | [110] |
Aquasomes | Self-assembled nanovesicles, composed of three layers. | [111] |
Colloidosomes | Hollow shell microcapsules composed of coagulated particles. | [112] |
Sphingosomes | Contained sphingolipids such as sphingosine, ceramide, sphingomyelin or glycosphingolipid; and are concentric, bilayered nanovesicles with an acidic pH inside. | [113] |
Ufasomes | Lipid carriers attach to the surface of the skin and support the lipid exchange between the outermost layers of the SC. | [114,115] |
Archeosomes | Consisted of archebacteria lipids, chemically distinct from eukaryotic and prokaryotic species. Less sensitive to high temperature, alkaline pH, and oxidative stress. | [116,117] |
Lipoplexes | Cationic lipid-DNA complexes. Efficient carriers for cell transfection. Toxic effects arising from either cationic lipids or nucleic acids. | [118] |
Proliposomes | Dry, free-flowing particles that immediately form a liposomal dispersion in contact with water. | [119,120] |
LNP Type | API/Drug | Application | Reference |
---|---|---|---|
Conventional liposomes | Licorice | Licorice-loaded liposomes included in the formulation for the treatment of oxidative stress injuries. | [146] |
Conventional liposomes | Quercetin and resveratrol | Quercetin- and resveratrol-loaded liposomes for the treatment of inflammatory/oxidative responses associated with skin cancer. | [147] |
Liposomes | Tretinoin | A tretinoin-loaded liposomal formulation for the treatment of acne. | [148] |
Liposomes | Benzoyl peroxide | Benzoyl peroxide and chloramphenicol encapsulation in liposomes for the treatment of acne. | [149] |
Liposomes | Benzoyl peroxide/Adapalene | Benzoyl peroxide- and adapalene-loaded modified liposomal gel for the treatment of acne. | [150] |
Transfersomes | Indocyanine green | Indocyanine green-loaded transfersomes for the treatment of acne vulgaris. | [151] |
Transfersomes | 5-Fluorouracil | 5-Fluorouracil-loaded transfersomes for the treatment of skin cancer. | [152] |
Transfersomes | Resveratrol and 5-fluorouracil | Transfersomes containing resveratrol and 5-fluorouracil for the treatment of skin cancer. | [145] |
Transfersomes | Amphotericin B | Development of amphotericin B-loaded transfersomes for antifungal and antileishmanial treatment. | [133] |
Transfersomes | siRNA | Transfersomes containing siRNA developed for delivery to the human basal epidermis for the treatment of melanoma. | [153] |
Transfersomes | RNAi | Transfersomes containing RNAi, formulated for the treatment of psoriasis. | [154] |
Transfersomes | Indocyanine | Indocyanine-loaded transfersomes for the treatment of basal cell carcinoma. | [155] |
Transfersomes | Clindamycin | Development of clindamycin-loaded transfersomes for the treatment of acne. | [156] |
Transfersomes | Paclitaxel | Paclitaxel containing transfersomes, modified by a cell-penetrating-peptide embedded in oligopeptide hydrogel for the topical treatment of melanoma. | [157] |
Transfersomes | Sodium stibogluconate | Transfersomes loaded with sodium stibogluconate for the treatment of leishmaniasis. | [158] |
Transfersomes | Lidocaine | Lidocaine transferosomal gel, containing permeation enhancers for local anesthetic action. | [159] |
Transfersomes | Sulforaphane | Transfersomes comprising sulforaphane for the treatment of skin cancer. | [160] |
Transfersomes | Miltefosine polyphenol | Formulation of miltefosine polyphenol-loaded transfersomes for the topical treatment of leishmaniasis. | [161] |
Transfersome | N-acetylcysteine | N-acetylcysteine-loaded transfersomes for antioxidant activity in anti-aging therapy. | [162] |
Ethosomes | Methoxsalen | Formulation of ethosomes containing methoxsalen for the topical treatment against vitiligo. | [134] |
Ethosomes | Griseofulvin | Design of griseofulvin-loaded ethosomes for enhanced antifungal treatment. | [163] |
Ethosomes | Cryptotanshinone | Cryptotanshinone-loaded ethosomes for anti-acne treatment. | [164] |
Ethosomes | Epigallocatechin-3-gallate | Epigallocatechin-3-gallate-loaded ethosomes for the treatment of skin cancer. | [165] |
Ethosomes | Thymoquinone | Thymoquinone-loaded ethosomes for the topical treatment of acne. | [166] |
Ethosomes | Clobetasol propionate | Ethosomes of clobetasol propionate for the treatment of eczema. | [167] |
Ethosomes | Tretinoin | Gel containing tretinoin-loaded ethosomes for anti-acne treatment. | [168] |
Ethosomes | Azelaic acid | Azelaic acid-loaded ethosomes for anti-acne treatment. | [137] |
Niosomes | Resveratrol | Resveratrol-loaded niosomes for the treatment of psoriasis. | [169] |
Niosomes | Diacerein | Niosomes for the topical diacerein delivery and treatment of psoriasis. | [170] |
Niosomes | Celastrol | Celastrol-loaded niosomes for the treatment of psoriasis. | [171] |
Cubosomes | Paclitaxel | Paclitaxel-loaded cubosomes against skin cancer. | [172] |
Cubosomes | Erythromycin | Erythromycin-loaded cubosomes for the treatment of acne. | [173] |
Hexosomes, cubosomes | Ketoconazole | Ketoconazole-loaded hexosomes for antifungal treatment. | [174] |
Ufasomes | Minoxidil | Minoxidil-loaded ufasomes for the treatment of hair loss. | [175] |
LNP Type | API/Drug | Application | Reference |
---|---|---|---|
SLN | Doxorubicin | Doxorubicin-loaded SLN for the treatment of skin cancer. | [206] |
SLN | Adapalene | Adapalene-loaded SLN in the gel for anti-acne treatment. | [207] |
SLN | Triamcinolone acetonide | Triamcinolone acetonide-loaded SLN for the topical treatment of psoriasis. | [208] |
SLN | Resveratrol, vitamin E, and epigallocatechin gallate | SLN containing resveratrol, vitamin E, and epigallocatechin gallate for antioxidant benefits. | [209] |
SLN | Silybin | Silybin-loaded SLN enriched gel for irritant contact dermatitis. | [210] |
SLN | Fluconazole | Fluconazole-loaded SLN topical gel for the treatment of pityriasis versicolor. | [211] |
SLN | Tazarotene | Tazarotene-loaded SLN for the treatment of psoriasis. | [212] |
SLN | Miconazole nitrate | Miconazole nitrate-loaded SLN for antifungal activity. | [213] |
SLN | Adapalene | Adapalene-loaded SLN for anti-acne therapy. | [214] |
SLN | Isotretinoin and α-tocopherol | SLN loaded with retinoic acid and lauric acid for the topical treatment of acne vulgaris. | [215] |
NLC | Spironolactone | Spironolactone-loaded NLC-based gel for the effective treatment of acne vulgaris. | [216] |
NLC | Clobetasol propionate | NLC-based topical gel of clobetasol propionate for the treatment of eczema. | [217] |
NLC | Tacrolimus and tumor necrosis factor α siRNA | NLC co-delivering tacrolimus and tumor necrosis factor α siRNA for the treatment of psoriasis. | [218] |
NLC | Itraconazole | Topical NLC containing itraconazole for the treatment of fungal infections. | [219] |
NLC | Apremilast | NLC for topical delivery of apremilast for the treatment of psoriasis. | [220] |
NLC | Dithranol | Dithranol-loaded NLC-based gel for the treatment of psoriasis. | [221] |
NLC | Voriconazole | Voriconazole-loaded NLC for antifungal applications. | [222] |
NLC | Mometasone furoate | NLC-based hydrogel of mometasone furoate for the treatment of psoriasis. | [223] |
NLC | Antimicrobial peptide nisin Z | Antimicrobial peptide nisin Z with conventional antibiotic-loaded NLC to enhance antimicrobial activity. | [224] |
NLC | Adapalene and vitamin C | Adapalene- and vitamin C-loaded NLC for acne treatment. | [225] |
Type | API/Drug | Application | Reference |
---|---|---|---|
Microemulsion | Tazarotene | Tazarotene-loaded microemulsion for the treatment of psoriasis. | [244] |
Microemulsion | Methotrexate | Methotrexate-loaded microemulsion for the treatment of psoriasis. | [245] |
Microemulsion | Retinoid | Retinoid-loaded microemulsion for the treatment of psoriasis. | [246] |
Microemulsion | Clotrimazole | Microemulsion coated with chitosan and containing clotrimazole for antifungal activity. | [247] |
Microemulsion | Griseofulvin | Griseofulvin-loaded microemulsion for the antifungal treatment. | [248] |
Microemulsion | Boswellia carterii oleo-gum-resin | Boswellia carterii oleo-gum resin-loaded microemulsion for the treatment of acne and eczema. | [249] |
Microemulsion | Indian pennywort, walnut, and turmeric | Topical dosage microemulsion of Indian pennywort, walnut, and turmeric for the treatment of eczema. | [250] |
Microemulsion | Triamcinolone | Microemulsion containing triamcinolone for transdermal delivery for the treatment of eczema. | [251] |
Microemulsion | Retinyl palmitate | Microemulsion containing retinyl palmitate for the treatment of acne, aging, and psoriasis. | [252] |
Nanoemulsion | Triptolide | Triptolide nanoemulsion gels for the treatment of eczema. | [253] |
Nanoemulsion | Ivermectin | Nanoemulsion containing ivermectin for the treatment of different types of parasite infestations. | [254] |
Nanoemulsion | Cyclosporine | Cyclosporine-loaded nanoemulsion for the treatment of psoriasis. | [255] |
Nanoemulsion | Coumestrol /Hydroxyethylcellulose | Nanoemulsion containing coumestrol and hydroxyethylcellulose for the treatment of antiherpes. | [256] |
Nanoemulsion | 8-Methoxypsoralen | 8-Methoxypsoralenloaded nanoemulsion for the treatment of vitiligo and psoriasis. | [257] |
Nanoemulsion | Coenzyme Q10 | Coenzyme Q10-loaded nanoemulsion as an antioxidant agent. | [258] |
Nanoemulsion | Psoralen | Psoralen-loaded nanoemulsion for the treatment of psoriasis and vitiligo. | [259] |
Nanoemulsion | Isotretinoin | Isotretinoin-loaded nanoemulsion for the treatment of acne. | [260] |
Nanoemulsion | Amphotericin B | Amphotericin B-loaded nanoemulsion for the antifungal treatment. | [261] |
Nanoemulsion | Zinc phthalocyanine | Zinc phthalocyanine-loaded nanoemulsion for use in photodynamic therapy for leishmaniasis. | [262] |
Type | API/Drug | Disease | Reference |
---|---|---|---|
Nanoemulsion gel | Clobetasol propionate | Treatments of psoriasis. | [266] |
Nanoethogel | Amphotericin B | Dermatophytes and fungal infections. | [236] |
Nanoemulsion gel | 5-Fluorouracil | Non-melanoma skin cancers. | [267] |
Hydrogel | Zinc oxide | Wound healing effect on fibroblast cells. | [268] |
Nanoemulgel, NLC | Vitamin E | Skin hydration. | [269] |
Hydrogel | Cyclosporine and calcipotriol | Treatments of psoriasis. | [270] |
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Stefanov, S.R.; Andonova, V.Y. Lipid Nanoparticulate Drug Delivery Systems: Recent Advances in the Treatment of Skin Disorders. Pharmaceuticals 2021, 14, 1083. https://doi.org/10.3390/ph14111083
Stefanov SR, Andonova VY. Lipid Nanoparticulate Drug Delivery Systems: Recent Advances in the Treatment of Skin Disorders. Pharmaceuticals. 2021; 14(11):1083. https://doi.org/10.3390/ph14111083
Chicago/Turabian StyleStefanov, Stefan R., and Velichka Y. Andonova. 2021. "Lipid Nanoparticulate Drug Delivery Systems: Recent Advances in the Treatment of Skin Disorders" Pharmaceuticals 14, no. 11: 1083. https://doi.org/10.3390/ph14111083