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1.
Photodiagnosis Photodyn Ther ; : 104298, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39089477

ABSTRACT

OBJECTIVE: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment. METHODS: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week. RESULTS: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88% for Group A, 62% for Group B, and 36% for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time. CONCLUSION: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects.

3.
Chem Biol Drug Des ; 104(2): e14598, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39090783

ABSTRACT

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1ß to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17ß-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.


Subject(s)
Acne Vulgaris , Aromatase , Furans , Lignans , Molecular Docking Simulation , Network Pharmacology , Animals , Furans/chemistry , Furans/pharmacology , Mice , Lignans/pharmacology , Lignans/chemistry , Lignans/therapeutic use , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Aromatase/metabolism , Aromatase/chemistry , Signal Transduction/drug effects , Skin/pathology , Skin/drug effects , Skin/metabolism , Inflammation/drug therapy , Inflammation/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Inflammasomes/metabolism , Humans , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Propionibacterium acnes/drug effects , Interleukin-1beta/metabolism , Disease Models, Animal
4.
J Dermatol ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39087744

ABSTRACT

Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α-dihydrotestosterone (5α-DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin- and 5α-DHT-differentiated hamster sebocytes. Ozenoxacin showed a dose-dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl-CoA desaturase-1, and perilipin-1 mRNA, all important factors involved in sebum synthesis, in a dose-dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin- and 5α-DHT-treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin-containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum-inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management.

5.
Int Immunopharmacol ; 140: 112795, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39096873

ABSTRACT

Acne is a chronic inflammatory skin disease with wide-ranging effects, involving factors such as Propionibacterium acnes (P. acnes) infection and sebum hypersecretion. Current acne treatments are challenged by drug resistance. 5-aminolaevulinic acid (ALA) -based photodynamic therapy (PDT) has been widely used in the clinical treatment of acne, however, the mechanism of its action remains to be elucidated. In this study, by constructing a mice ears model of P. acnes infection, we found that ALA-PDT inhibited the proliferation of P. acnes in vivo and in vitro, significantly ameliorated ear swelling, and blocked the chronic inflammatory process. In vitro, ALA-PDT inhibited lipid secretion and regulated the expression of lipid synthesis and metabolism-related genes in SZ95 cells. Further, we found that ALA-PDT led to DNA damage and apoptosis in SZ95 cells by inducing mitochondrial stress and oxidative stress. Altogether, our study demonstrated the great advantages of ALA-PDT for the treatment of acne and revealed that the mechanism may be related to the blockade of chronic inflammation and the suppression of lipid secretion by ALA-PDT.

6.
J Cosmet Dermatol ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39092840

ABSTRACT

BACKGROUND: The severity and treatment response of acne, melasma, and rosacea may be influenced by various currently unclear internal and external factors. This study aimed to provide evidence to the influencing factors for the mentioned conditions through a real-world case-control study. METHODS: An online survey consisting of 60 questions was implemented, collecting information on demographics, socioeconomics, genetic factors, lifestyle habits, environmental exposures, and skin care behaviors. Then we constructed univariate and multivariate logistic regressions. Furthermore, we analyzed the dose-response relationship between exposure and outcome. RESULTS: A total of 399 individuals, including 94 acne patients, 107 melasma patients, and 91 rosacea patients were included. Acne and melasma were positively correlated with screen time (acne: odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.25-4.02; melasma: OR: 1.59, 95% CI: 1.09-2.31), while exercise exerted a protective effect on both acne (OR: 0.31, 95% CI: 0.13-0.77) and melasma (OR: 0.42, 95% CI: 0.22-0.80) in a dose-response relationship. In addition, males were associated with an elevated risk of acne (OR: 6.62, 95% CI: 1.01-43.26). Aging (OR: 1.15, 95% CI: 1.07-1.24) and irregular bowel movements (OR: 2.99, 95% CI: 1.11-8.08) were independent risk factors for melasma. Rosacea was positively associated with BMI (OR: 1.17, 95% CI: 1.01-1.35). CONCLUSION: In our study, we highlighted exercise as an independent protective factor for both acne and melasma in a dose-response trend. Inversely, extended use of electronic equipment was independently associated with higher risks of acne and melasma. Rosacea, however, was more likely to be related with BMI.

7.
Article in English | MEDLINE | ID: mdl-39107673

ABSTRACT

We demonstrated for the first time that a marine-derived antimicrobial peptide (AMP), Sph12-38, exhibit high antimicrobial activity against P. acnes with a minimum bactericidal concentration (MBC) value of 7 µM. Meanwhile, Sph12-38 has no significant cytotoxicity to human keratinocytes (HKs) at its high concentration (33.5 µM). The topical application of sponge Haliclona sp. spicules (SHS) dramatically enhanced the skin penetration of Sph12-38 up to 40.9 ± 5.9% (p < 0.01), which was 6.1 ± 0.9-fold higher than that of Sph12-38 alone. Further, SHS resulted in the accumulation of most Sph12-38 in viable epidermis and dermis. Further, the combined use of Sph12-38 and SHS resulted in a cure rate of 100% for rabbit ear acne treatment in vivo for two weeks, while the one induced by other groups was 40%, 0% and 0% for SHS alone, Sph12-38 alone and control group, respectively. The strategy of combined using AMP and SHS can also be applied in a rational designed topical delivery system for the management of other deep infection of the skin. The effectiveness of SHS by itself on the treatment of acne was also demonstrated by clinical trials. After 14 days of treatment by 1% SHS gel. The number of skin lesions decreased by 51.4%.

8.
Arch Dermatol Res ; 316(8): 505, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39110247

ABSTRACT

This study aimed to analyze the efficacy and safety of microneedling (MN), both alone and in combination with other treatments, to refine the approach for treating acne scars using MN. We systematically searched Pubmed, Cochrane Library, Embase, and Web of Science for randomized controlled trials examining MN or its combinations in patients with acne scars. All statistical analyses were performed using Stata 18 software. A total of 24 studies involving 1546 participants were included. The analysis revealed that MN combined with chemical peels (CP) exhibited the best results in terms of degree of improvement, patient satisfaction, and treatment efficacy compared to other treatments examined, including MN alone, MN with hyaluronic acid (HA), MN with botulinum toxin­A (TA), MN with platelet-rich plasma (PRP), PRP alone, CP, and laser therapy. The results for MN combined with additional treatments were obviously better than for MN alone. Side effects such as erythema, pain, and post-inflammatory hyperpigmentation showed no significant differences across all treatments assessed.


Subject(s)
Acne Vulgaris , Cicatrix , Needles , Network Meta-Analysis , Randomized Controlled Trials as Topic , Humans , Acne Vulgaris/complications , Acne Vulgaris/therapy , Treatment Outcome , Combined Modality Therapy/methods , Cicatrix/etiology , Cicatrix/therapy , Cicatrix/diagnosis , Needles/adverse effects , Patient Satisfaction , Chemexfoliation/methods , Chemexfoliation/adverse effects , Dry Needling/methods , Dry Needling/adverse effects , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/adverse effects , Platelet-Rich Plasma , Laser Therapy/methods , Laser Therapy/adverse effects , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/adverse effects , Percutaneous Collagen Induction
10.
Pediatr Dermatol ; 2024 Aug 04.
Article in English | MEDLINE | ID: mdl-39098006

ABSTRACT

Eczema can manifest in a linear arrangement, as can other inflammatory conditions. We report a case of a teenager who, during treatment with oral isotretinoin for acne, developed a generalized eczematous dermatitis together with a superimposed linear eczema on her posterior lower limb. We hypothesize that a postzygotic mutation caused an increased sensitivity to the impact of oral isotretinoin on the epidermal skin barrier structure and lipid composition within a specific skin segment.

11.
Arch Dermatol Res ; 316(8): 504, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39101981

ABSTRACT

Observational studies have shown a strong association between circulating white blood cell counts (WBC) and inflammatory skin diseases such as acne and psoriasis. However, the causal nature of this relationship is unclear. We performed a two-way two-sample Mendelian randomization (MR) analysis to investigate potential causal relationships between leukocytes and inflammatory skin diseases. The circulating white blood cell count, basophil cell count, leukocyte cell count, lymphocyte cell count, eosinophil cell count, and neutrophil cell count data were obtained from the Blood Cell Consortium (BCX). The data for inflammatory skin disorders, including acne, atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis, and seborrheic dermatitis (SD), were obtained from the FinnGen Consortium R10. The primary analysis utilized inverse variance weighting (IVW) along with additional methods such as MR-Egger, weighted mode, and weighted median estimator. To assess heterogeneity among instrument variables, Cochran's Q test was employed, while MR-Egger intercept and MR-PRESSO were used to test for horizontal pleiotropy. IVW demonstrated that an elevated monocyte count was significantly associated with a decreased risk of psoriasis (OR = 0.897, 95% CI: 0.841-0.957, P = 0.001, FDR = 0.016). Additionally, an increased eosinophil count was causally associated with a higher risk of AD (OR = 1.188, 95% CI: 1.093-1.293, P = 0.000, FDR = 0.002). No inverse causal relationship between inflammatory skin disease and circulating white blood cell count was found. In conclusion, this study provides evidence that increased monocyte count is associated with a reduced risk of psoriasis and that there is a causal relationship between increased eosinophil counts and an increased risk of AD. These findings help us understand the potential causal role of specific white blood cell counts in the development of inflammatory skin diseases.


Subject(s)
Mendelian Randomization Analysis , Psoriasis , Humans , Leukocyte Count , Psoriasis/genetics , Psoriasis/blood , Psoriasis/immunology , Psoriasis/diagnosis , Eosinophils/immunology
12.
Front Microbiol ; 15: 1424849, 2024.
Article in English | MEDLINE | ID: mdl-38974030

ABSTRACT

Introduction: A total of 94 Propionibacterium acnes (P. acnes) isolates were obtained from a hospital in Beijing to evaluate their susceptibility to erythromycin, clarithromycin, doxycycline, and minocycline. As well as the determination of the effectiveness of P. acnes phages in vitro and in P. acnes-induced lesions mouse model. Methods: Patients with acne vulgaris (AV) were enrolled from August 2021 to October 2022. Standard methods were employed for specimen collection, culture, and identification of P. acnes. Susceptibility testing was conducted using E-strips for erythromycin, clarithromycin, minocycline, and doxycycline. Phage culture and identification followed standard procedures. A mouse model with P. acnes-induced skin lesions was established, and data was analyzed using χ 2 test. Results: The results showed that all isolates were susceptible to minocycline and doxycycline, while 53 (56.4%) and 52 (55.3%) isolates were susceptible to erythromycin and clarithromycin, respectively. Interestingly, younger patients and those with lower acne severity exhibited reduced resistance. Phage cleavage rates ranged from 88.30 to 93.60%. Multilocus sequence typing (MLST) analysis was conducted on eight randomly selected P. acnes isolates, and the IA-2 subtype was used in experiments to address P. acnes-induced lesions in mice. Phage therapy proved effective in this model. Discussion: This study highlights the high susceptibility of P. acnes to doxycycline and tetracycline, while erythromycin and clarithromycin exhibited elevated resistance. Additionally, P. acnes phages demonstrated high cleavage rates and potential effectiveness in treating P. acnes-induced lesions. These findings suggest promising avenues for further exploration of phage therapy in acne treatment.

13.
J Asian Nat Prod Res ; : 1-13, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952150

ABSTRACT

Inhibition of lipid synthesis in sebocytes is essential for acne treatments. The effects of natural product-derived substances on lipid synthesis are unknown. This study investigated the effects of water extract of Mangifera indica leaves (WEML) on lipid synthesis in human sebocytes. Sebocyte differentiation in low serum conditions increased lipid accumulation and proliferator-activated receptor γ expression. WEML treatment significantly inhibited lipid accumulation and adipogenic mRNA expression in sebocytes. Mangiferin, a bioactive compound in WEML, also reduced lipid accumulation and adipogenic mRNA expression via the AKT pathway. Thus, WEML and mangiferin effectively inhibit lipid synthesis in sebocytes, showing promise for acne treatment.

14.
Lasers Med Sci ; 39(1): 168, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954141

ABSTRACT

PURPOSE: Several treatment options for acne vulgaris are limited by their associated adverse effects. An innovative approach involves introducing light-absorbing nanoparticles into sebaceous follicles before destroying the follicles using selective photothermolysis. We aimed to investigate efficient methods for introducing gold and platinum nanoparticles into sebaceous follicles and to identify suitable laser equipment and parameters for the effective destruction of these follicles. METHODS: We used porcine skin as the experimental model. We compared the efficacies of a thulium laser, ultrasound, and manual massage and evaluated the optimal method for delivering nanoparticles in close proximity to sebaceous follicles. Subsequently, a 1064-nm-wavelength neodymium-doped yttrium aluminum garnet (Nd: YAG) laser was employed to induce selective photothermolysis. We compared different parameters to identify the optimal pulse duration and fluence of the Nd: YAG laser. The extent of penetration and destruction of sebaceous follicles was assessed using hematoxylin and eosin (H&E) staining, and a numerical evaluation was conducted. RESULTS: H&E staining showed that irradiation with a long-pulsed Nd: YAG laser following a combination of thulium laser and sonophoresis effectively destroyed sebaceous follicles, with destruction rates exceeding 50%. These results were valid with a long pulse duration and a high fluence of the Nd: YAG laser. CONCLUSION: This study demonstrated that sebaceous follicles can be effectively destroyed through a mixture of gold and platinum nanoparticle delivery by a combination of microchanneling and sonophoresis, followed by selective thermal damage induced by a 1064-nm long-pulsed high-fluence Nd: YAG laser.


Subject(s)
Acne Vulgaris , Gold , Lasers, Solid-State , Metal Nanoparticles , Platinum , Animals , Gold/administration & dosage , Swine , Pilot Projects , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Acne Vulgaris/therapy , Lasers, Solid-State/therapeutic use , Skin/radiation effects , Sebaceous Glands/radiation effects , Sebaceous Glands/drug effects , Sebaceous Glands/pathology
15.
Int J Womens Dermatol ; 10(3): e163, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38957412

ABSTRACT

Background: Acne is an inflammatory condition of the pilosebaceous unit. Previous studies have established a link between acne and vitamin D deficiency and the potential effectiveness of vitamin D supplementation in treatment. However, the efficacy of vitamin D as an adjuvant treatment for acne remains unknown. Objective: To evaluate the efficacy of weekly vitamin D2 oral administration as an adjunctive treatment to standard topical care for acne. Methods: This study was a randomized, double-blind, placebo-controlled trial including subjects with mild-to-moderate acne. Topical 2.5% benzoyl peroxide was applied twice daily for 12 weeks to all subjects. Subjects were randomly allocated to receive either oral vitamin D2 40,000 IU weekly or placebo weekly during the treatment period. No additional treatment was administered during the 4-week follow-up period. Results: A total of 44 subjects were included in this study. All of them had inadequate 25(OH)D levels. Both regimens showed significant improvement in acne during the treatment period. Weekly vitamin D2 supplementation significantly prevented the relapse of inflammatory acne lesions (P = .048) at the follow-up visit. No adverse effects or biochemical changes were observed. Limitations: There were no subjects of severe acne vulgaris. Conclusion: Adjunctive weekly vitamin D2 supplementation to standard topical benzoyl peroxide could reduce relapses of inflammatory lesions in mild-to-moderate acne.

17.
Heliyon ; 10(11): e32468, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38961914

ABSTRACT

A simple method to generate antibacterial peptides by alkaline hydrolysis of hen egg whites is reported. The method reproducibly generates short peptides with molecular weight of less than 14.4 kDa that exhibit low to no cytotoxicity on RAW 264.7 macrophage cells, but do inhibit the bacterial growth of Cutibacterium acnes (C. acnes), Staphylococcus aureus (S. aureus) and antibiotic-resistant S. aureus (MRSA), while also reducing nitric oxide production from heat-killed C. acnes-treated RAW 264.7 cells. Peptidomics revealed at least thirty peptides within the complex mixture, of which eight were evaluated individually. Three peptides (PK8, EE9 and RP8) were potent anti-inflammation and antibacterial agents, but notably the complex egg white hydrolysate (EWH) was more effective than the individual peptides. Electron microscopy suggests the antibacterial mechanism of both the hydrolysate and the selected peptides is through disruption of the cell membrane of C. acnes. These findings suggest that EWH and EWH-derived peptides are promising candidates for infection and inflammation treatment, particularly in managing acne and combating antibiotic-resistant bacteria like MRSA.

18.
Skin Therapy Lett ; 29(4): 5-7, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38963912

ABSTRACT

Acne is a common inflammatory condition of the skin worldwide. The skin is an endocrine organ and hormones are a key pathogenic factor in all types of acne with a particularly important role in adult female acne pathogenesis and management. In females, we have the unique opportunity to manipulate hormones systemically to successfully manage acne and, more recently with the approval of clascoterone 1% cream, we can target the hormones topically in both genders. The intent of this paper is to provide physicians with an up-to-date clinically relevant review of the role of hormones in acne, the impact of currently available contraceptives and therapies available to target hormones in acne.


Subject(s)
Acne Vulgaris , Humans , Acne Vulgaris/drug therapy , Female , Adult , Cortodoxone/therapeutic use , Cortodoxone/analogs & derivatives , Propionates
19.
Skin Therapy Lett ; 29(4): 1-4, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38963911

ABSTRACT

Acne vulgaris is a common, often chronic inflammatory disease that can affect all ages and skin tones. Beyond acute lesions, the sequelae of acne - specifically scarring and dyspigmentation - can be long-lasting, challenging to treat and have substantial psychosocial impact on affected individuals. For acne scarring, treatment modalities include topical, physical, and laser and light therapies, with combination approaches typically yielding optimal outcomes. Trifarotene is a novel fourth generation retinoid with targeted action towards retinoid acid receptor gamma (RAR-γ), the most common isotype found in the epidermis, that has previously been approved for the management of moderate-to-severe facial and truncal acne in individuals over the age of 12 years. Recently, data on trifarotene supports its application in acne scarring. Herein, we provide a succinct review on various treatments for acne scarring and explore how trifarotene and its mechanism of action present an additional topical approach to target atrophic acne scarring.


Subject(s)
Acne Vulgaris , Cicatrix , Retinoids , Humans , Acne Vulgaris/complications , Acne Vulgaris/drug therapy , Cicatrix/drug therapy , Cicatrix/etiology , Retinoids/therapeutic use , Dermatologic Agents/therapeutic use , Dermatologic Agents/administration & dosage , Atrophy , Administration, Cutaneous
20.
Drug Deliv ; 31(1): 2372269, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38956885

ABSTRACT

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.


Subject(s)
Acne Vulgaris , Drug Carriers , Hair Follicle , Polymers , Hair Follicle/drug effects , Hair Follicle/metabolism , Acne Vulgaris/drug therapy , Humans , Polymers/chemistry , Drug Carriers/chemistry , Drug Delivery Systems/methods , Nanoparticles , Administration, Cutaneous , Animals , Nanoparticle Drug Delivery System/chemistry
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