RESUMO
Dual photothermal and photodynamic therapy (PTT and PDT) is an attractive approach that generates a synergistic effect for inhibiting keratinocyte hyperproliferation in the treatment of psoriasis. Here, we developed phototheranostic nanocarriers capable of producing hyperthermia and reactive oxygen species (ROS) in response to near-infrared (NIR) illumination. To this end, IR820 with photothermal and photodynamic features was embedded in nano-sized polydopamine (PDA) acting as a PTT agent. A comprehensive characterization of the PDA/IR820 nanosystem was performed according to its morphology, size, zeta potential, UV absorbance, and heat generation. Its therapeutic efficacy was assessed by a keratinocyte-based study and using an imiquimod (IMQ)-stimulated psoriasiform murine model. PDA/IR820 nanoparticles were facilely internalized into keratinocytes and mainly resided in lysosomes. Upon irradiation with NIR light, ROS were generated inside the keratinocytes to cause a photodynamic effect. The live/dead cell assay and cytotoxicity assay demonstrated that PDA and IR820 acted as effective photoabsorbers to induce keratinocyte death. The highest cytotoxic effect was detected in the group of NIR-irradiated PDA/IR820 nanoparticles, which killed 52% of keratinocytes. The nanosystem acted through the caspase and poly ADP-ribose polymerase (PARP) pathways to induce keratinocyte apoptosis. In vitro and in vivo skin permeation indicated the selective accumulation of the topically applied PDA/IR820 nanoparticles within psoriasiform skin, suggesting their skin-targeting capability. The combination of PDA/IR820 nanoparticles and NIR irradiation increased the skin temperature by 11.7 °C. PTT/PDT eliminated psoriasiform plaques in mice by decreasing hyperplasia, inhibiting cytokine overexpression, and recovering the barrier function. The epidermal thickness of the IMQ-treated skin was reduced from 134 to 34 µm by the nanocarriers plus NIR. The IR820 nanoparticles were largely deposited on the inflamed areas of psoriasiform lesions for monitoring the severity of inflammation. The image-guided phototheranostic nanoparticles showed their potential for applications in psoriasis management via noninvasive topical administration.
Assuntos
Hipertermia Induzida , Nanopartículas , Fotoquimioterapia , Psoríase , Camundongos , Animais , Espécies Reativas de Oxigênio , Imiquimode , Inibidores de Poli(ADP-Ribose) Polimerases , Verde de Indocianina/farmacologia , Camundongos Endogâmicos BALB C , Psoríase/tratamento farmacológico , Caspases , Citocinas , Adenosina Difosfato RiboseRESUMO
Psoriasis is an autoimmune skin disorder presenting the excessive expression of interleukin (IL)-6. The topical use of small interfering RNA (siRNA) has been increasingly discovered for treating skin diseases. A delivery system capable of protecting siRNA while facilitating both skin targeting and cellular entrance is critical for the successful medication of topically-applied siRNA. Herein, we developed a delivery system for siRNA based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles and combined this system with an ablative laser to promote skin absorption for topical psoriasis therapy. The siRNA absorption enhancement was compared by two laser modalities: a fractional CO2 laser and a fully-ablative Er:YAG laser. We characterized the effect of the delivery system by the cellular uptake, IL-6 silencing, in vitro skin absorption, cutaneous biodistribution, and in vivo psoriasiform dermatitis in mice. The nanocarriers showed minimal cytotoxicity and facile cellular uptake to knock down the IL-6 expression. The nanoformulation containing a cationic surfactant (Forestall) for ion pairing with siRNA achieved a 66% and 77% IL-6 knockdown efficiency toward keratinocytes and macrophages, respectively. In the Franz cell absorption, the lasers increased the naked siRNA penetration to the receptor compartment by 3.7-5.0-fold but remarkably reduced skin deposition using imiquimod (IMQ)-treated psoriasiform skin as the barrier. The fractional laser facilitated nanoparticle-associated siRNA skin deposition up to 3.3-fold, whereas the transport of the nanocarriers to the receptor was negligible. Qualitatively, the lasers increased nanoparticle delivery in the epidermis with limited effect to elevate the penetration depth. The fractional-mediated nanocarrier delivery dramatically attenuated the erythema and scaly lesions of psoriasiform dermatitis. The histological examination displayed a reduction of epidermal hyperplasia and macrophage infiltration by the combination of laser and nanosystem. The passive and laser-assisted naked siRNA delivery was less effective in mitigating dermatitis. The topical delivery of fractional laser-assisted nanoparticles on mice resulted in a 56% IL-6 knockdown. Our results manifested the benefit of cutaneous siRNA targeting using ablative lasers to deliver nanocarriers for treating psoriatic inflammation.
Assuntos
Dermatite , Lasers de Estado Sólido , Psoríase , Administração Cutânea , Animais , Dermatite/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Nanopartículas , Psoríase/tratamento farmacológico , RNA Interferente Pequeno , Distribuição TecidualRESUMO
Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-ß1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.
Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Plasma Rico em Plaquetas/metabolismo , Envelhecimento da Pele/efeitos da radiação , Dermatopatias/terapia , Pele/efeitos da radiação , Infecções Cutâneas Estafilocócicas/terapia , Administração Cutânea , Animais , Terapia Combinada , Citocinas/farmacocinética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacocinética , Lasers de Gás/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea/efeitos da radiação , Envelhecimento da Pele/efeitos dos fármacos , Suínos , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiaçãoRESUMO
While isotretinoin has been the gold-standard of therapy for severe acne since its approval in 1982, its anti-inflammatory properties makes it a potentially applicable and versatile therapy for a wide variety of dermatologic conditions yet to be explored. This systematic review comprehensively recounts the success of oral isotretinoin in non-acne cutaneous diseases and provide insight into future directions of isotretinoin utility. A systematic literature review was performed using PubMed. Search terms included "isotretinoin" OR "accutane" AND "skin" OR "dermatology" OR "hair" OR "nails" OR "rosacea" OR "psoriasis" OR "pityriasis rubra pilaris" OR "condyloma acuminata" OR "granuloma annulare" OR "darier's disease" OR "non-melanoma skin cancer" OR "frontal fibrosing alopecia" OR "cutaneous lupus erythematosus" OR "hidradenitis suppurativa" OR "photodamaged skin" OR "skin aging" OR "wart" OR "flat warts" OR "plane warts" OR "lichen planus" OR "dissecting cellulitis" OR "folliculitis decalvans" OR "sebaceous hyperplasia" OR "cutaneous t-cell lymphoma" OR "mycosis fungoides." A total of 169 studies discuss the use of oral isotretinoin for 16 non-acne dermatologic conditions, the most common being non-melanoma skin cancers (0.2-8.2 mg/kg/day), cutaneous T-cell lymphomas (0.5-2 mg/kg/day), and rosacea (0.22-1 mg/kg/day). Inflammatory conditions such as rosacea, granuloma annulare, and hidradenitis suppurativa benefit from lower oral isotretinoin dosage of 0.3-1 mg/kg/day, whereas, hyperkeratotic diseases such as psoriasis and pityriasis rubra pilaris, consistently respond better to higher dosages of up to 2-4 mg/kg/day for lesion clearance. Recurrence of disease following discontinuation of isotretinoin have been reported for rosacea, psoriasis, granuloma annulare, Darier's disease, dissecting cellulitis, and non-melanoma skin cancers. Disease exacerbation was reported in some patients with hidradenitis suppurativa. Off-label isotretinoin is an effective treatment choice for dermatological conditions beyond acne. Further prospective, randomized human trials are needed to clarify when and how to prescribe off-label isotretinoin for maximum efficacy and safety.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Isotretinoína/administração & dosagem , Uso Off-Label , Dermatopatias/tratamento farmacológico , Administração Oral , Fármacos Dermatológicos/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Isotretinoína/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Injectable deoxycholic acid (DCA) may be used to remove excess submental fat and off-label for local adipose reduction. Despite DCA's widespread use, rare incidences of severe, systemic, long-term adverse events (AEs) have been reported. OBJECTIVE: To evaluate the potential side effects associated with injectable DCA. METHODS AND MATERIALS: A systematic review was conducted using PubMed, Cochrane, CINAHL, and Web of Science using PRISMA guidelines to gather the literature relating to DCA or deoxycholate-associated AEs and their management. RESULTS: Twenty-eight manuscripts were included after full article review. Most commonly, patients experienced mild localized AEs, whereas a small number of patients experienced severe pain, alopecia, nasopharyngitis, dysphagia, dizziness/lightheadedness, and gastrointestinal upset. Severe, long-term AEs were reported as rare in the evaluated literature. Deoxycholic acid injections in large volumes were more likely to cause severe adverse effects. CONCLUSION: Self-resolving, mild side effects and severe but rare adverse effects have been reported with DCA use making it a safe treatment for local adipose reduction. Further studies are necessary to determine its safety profile, especially when using DCA in off-label areas.
Assuntos
Técnicas Cosméticas , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/administração & dosagem , Ácido Desoxicólico/uso terapêutico , Humanos , InjeçõesRESUMO
BACKGROUND: Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE: To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS: A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS: A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS: This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION: The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
Assuntos
Vacinas Anticâncer/uso terapêutico , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/uso terapêutico , Neoplasias/tratamento farmacológico , Verrugas/tratamento farmacológico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Feminino , Humanos , Infecções por Papillomavirus/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias Vulvares/tratamento farmacológico , Displasia do Colo do Útero/tratamento farmacológicoRESUMO
Introduction: Injectable deoxycholic acid (DCA; Kybella; Allergan, Irvine, CA) is currently approved only for treatment of persistent submental fat (SMF). Many cosmetic surgeons use DCA off-label to treat fat tissue in other areas of the body. There is no review summarizing the off-label uses of injectable DCA. Methods: A systematic literature search was conducted through PubMed, Cochrane, CINAHL, and Web of Science databases using search terms "ATX-101 OR Kybella OR deoxycholic OR deoxycholate NOT amphotericin NOT bile" in accordance to PRISMA guidelines to identify off-label uses for injectable DCA or ATX-101. Results: Ten pertinent articles were identified for review. Anatomic areas treated include the face, brassiere line, foot, and gluteotrochanteric region. Indications include facial contouring, paradoxical adipose hyperplasia, HIV/HAART-associated buccal fat pad lipodystrophy, and reduction of lipomatous tumors. DCA is efficacious at causing lipolysis and safe with minimal side effects. Most patients treated for cosmetic indications reported high patient satisfaction. Conclusion: Off-label use of injectable DCA demonstrate a similar safety profile, effectiveness, and overall patient satisfaction compared to FDA-approved use for persistent SMF. DCA appears to be a safe and efficacious alternative to surgical reduction of unwanted adipose tissue in non-submental areas. Larger-scale studies are warranted to explore further cosmetic and potential medical applications. J Drugs Dermatol. 2019;18(7):675-680.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Técnicas Cosméticas/efeitos adversos , Ácido Desoxicólico/administração & dosagem , Uso Off-Label , Nádegas , Ácido Desoxicólico/efeitos adversos , Estética , Face , Pé , Humanos , Injeções Subcutâneas/efeitos adversos , Lipólise/efeitos dos fármacos , Satisfação do Paciente , Resultado do TratamentoRESUMO
Allergic contact dermatitis is a common disease within the family of delayed-type hypersensitivity reactions. In more severe cases of allergic contact dermatitis, topical steroids may prove insufficient, and systemic therapeutic agents are often used. Even when systemic therapies such as cyclosporine lead to improvement, withdrawal of these agents is challenging and can lead to undesirable morbidities. Currently, there are no systemic treatments indicated for the treatment of widespread recalcitrant contact dermatitis. This review discusses the targets of in-use off-label systemic medications and potential therapeutics in the pipeline.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Dermatite Alérgica de Contato/tratamento farmacológico , Imunossupressores/uso terapêutico , Adalimumab/uso terapêutico , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Infliximab/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Uso Off-Label , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The terms composite and collision tumors have been used interchangeably throughout radiological literature. Both composite and collision tumors involve two morphologically and immunohistochemically distinct neoplasms coexisting within a single organ. However, collision tumors lack the histological cellular intermingling seen in composite tumors. Composite tumors often arise from a common driver mutation that induces a divergent histology from a common neoplastic source while collision tumors may arise from coincidental neoplastic change. The purpose of this review is to provide an overview of abdominal composite and collision tumors by discussing hallmark radiographic and pathological presentations of rare hepatic, renal, and adrenal case studies. A better understanding of the presentation of each lesion is imperative for proper recognition, diagnosis, and management of these unique tumor presentations.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Humanos , FenótipoRESUMO
A cationic amphiphile, soyaethyl morpholinium ethosulfate (SME), immobilized in liposomes or nanoemulsions, was prepared in an attempt to compare the antibacterial activity between SME intercalated in the phospholipid bilayer and oil-water interface. Before antibacterial assessment, the size of the liposomes and nanoemulsions was respectively recorded as 75 and 214 nm. The data of minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) and live/dead cell count demonstrated a superior antimicrobial activity of nanoemulsions compared to liposomes against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Staphylococcus epidermidis. Nanoemulsion incubation reduced biofilm thickness by 2.4-fold, whereas liposomes showed a 1.6-fold decrease in thickness. SME insertion in the oil-water phase was found to induce bacterial membrane disruption. SME nanosystems were nontoxic to keratinocytes. In vivo topical application of the cationic nanosystems reduced skin infection, MRSA load, and inflammation in mice. The deteriorated skin barrier function evoked by MRSA was recovered by nanoemulsion treatment.
Assuntos
Biofilmes , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanoestruturas , Animais , Antibacterianos , Camundongos , Testes de Sensibilidade Microbiana , Plâncton , Staphylococcus aureusRESUMO
[This corrects the article on p. 241 in vol. 5, PMID: 24904554.].
RESUMO
Bacteriocins are a kind of ribosomal synthesized antimicrobial peptides produced by bacteria, which can kill or inhibit bacterial strains closely-related or non-related to produced bacteria, but will not harm the bacteria themselves by specific immunity proteins. Bacteriocins become one of the weapons against microorganisms due to the specific characteristics of large diversity of structure and function, natural resource, and being stable to heat. Many recent studies have purified and identified bacteriocins for application in food technology, which aims to extend food preservation time, treat pathogen disease and cancer therapy, and maintain human health. Therefore, bacteriocins may become a potential drug candidate for replacing antibiotics in order to treat multiple drugs resistance pathogens in the future. This review article summarizes different types of bacteriocins from bacteria. The latter half of this review focuses on the potential applications in food science and pharmaceutical industry.
RESUMO
Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related cells is important in the treatment of alopecia. Here we report the development of "squarticles," nanoparticles formed from sebum-derived lipids such as squalene and fatty esters, for use in achieving targeted drug delivery to the follicles. Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions (NE), were prepared. The physicochemical properties of squarticles, including size, zeta potential, drug encapsulation efficiency, and drug release, were examined. Squarticles were compared to a free control solution with respect to skin absorption, follicular accumulation, and dermal papilla cell targeting. The particle size of the NLC type was 177 nm; that of the NE type was 194 nm. Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles. An improved drug deposition in the skin was observed in the in vitro absorption test. Compared to the free control, the squarticles reduced minoxidil penetration through the skin. This may indicate a minimized absorption into systemic circulation. Follicular uptake by squarticles was 2- and 7-fold higher for DPCP and minoxidil respectively compared to the free control. Fluorescence and confocal images of the skin confirmed a great accumulation of squarticles in the follicles and the deeper skin strata. Vascular endothelial growth factor expression in dermal papilla cells was significantly upregulated after the loading of minoxidil into the squarticles. In vitro papilla cell viability and in vivo skin irritancy tests in nude mice suggested a good tolerability of squarticles to skin. Squarticles provide a promising nanocarrier for topical delivery of DPCP and minoxidil.
Assuntos
Ciclopropanos/administração & dosagem , Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos , Folículo Piloso/metabolismo , Minoxidil/administração & dosagem , Vasodilatadores/administração & dosagem , Animais , Células Cultivadas , Ciclopropanos/farmacocinética , Feminino , Humanos , Camundongos , Camundongos Nus , Microscopia Confocal , Microscopia de Fluorescência , Minoxidil/farmacocinética , Nanopartículas/química , Sebo/química , Testes de Irritação da Pele , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vasodilatadores/farmacocinéticaRESUMO
Multifunctional liposomes loaded with quantum dots (QDs) and anticancer drugs were prepared for simultaneous bioimaging and drug delivery. Different formulations, including cationic, PEGylated and deformable liposomes, were compared for their theranostic efficiency. We had evaluated the physicochemical characteristics of these liposomes. The developed liposomes were examined using experimental platforms of cytotoxicity, cell migration, cellular uptake, in vivo melanoma imaging and drug accumulation in tumors. The average size of various nanocomposite liposomes was found to be 92134 nm. Transmission electron microscopy confirmed the presence of QDs within liposomal bilayers. The incorporation of polyethylene glycol (PEG) and Span 20 into the liposomes greatly increased the fluidity of the bilayers. The liposomes provided sustained release of camptothecin and irinotecan. The cytotoxicity and cell migration assay demonstrated superior activity of cationic liposomes compared with other carriers. Cationic liposomes also showed a significant fluorescence signal in melanoma cells after internalization. The liposomes were intratumorally administered to a melanoma-bearing mouse. Cationic liposomes showed the brightest fluorescence in tumors, followed by classical liposomes. This signal could last for up to 24 h for cationic nanosystems. Intratumoral accumulation of camptothecin from free control was 35 nmol g(−1); it could be increased to 50 nmol g(−1) after loading with cationic liposomes. However, encapsulation of irinotecan into liposomes did not further increase intratumoral drug accumulation. Cationic liposomes were preferable to other liposomes as nanocarriers in both bioimaging and therapeutic approaches.