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1.
Wound Repair Regen ; 28(4): 460-469, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32428986

RESUMO

Hypertrophic scar is an important clinical problem with limited therapeutic options. Aside from their roles as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, statins have also been demonstrated to decrease scarring by reducing connective tissue growth factor (CTGF) expression. However, poor penetrative ability limits their utility as topical treatments for hypertrophic scar. Here, we aim to develop novel statin formulations using liposomes to enhance dermal penetrative ability and to evaluate their efficacy against formation of hypertrophic scar utilizing our validated rabbit ear hypertrophic scar model. Liposomal simvastatin or pravastatin were compounded using a novel, flexible liposomal formulation and applied topically to rabbit ear hypertrophic scars daily from postoperation day (POD) 14 until POD 25. Scar color, including erythema and melanin, was measured using reflectance spectrophotometry on POD 28, and scar tissue was harvested for evaluation of scar elevation index as well as gene and protein expression. Human foreskin fibroblasts were also treated with statin formulations and CCN2 expression was determined by quantitative PCR. Both simvastatin and pravastatin were efficiently encapsulated in liposomes, forming nanometer-scale particles possessing highly negative charges. Topical treatment with liposomal simvastatin and pravastatin at 6.5% concentration significantly reduced scar elevation index and decreased type I/III collagen content and myofibroblast persistence in the wound. The erythema/vascularity of scars was reduced by liposomal statin treatment, with concomitant decrease of CD31 expression as measured histologically. Expression levels of transcripts encoding CTGF, collagen I, and collagen III collagen in scar tissue were also decreased by liposomal pravastatin treatment, as were myofibroblast persistence and the type I/III collagen ratio as assessed by immunofluorescence and picrosirus red staining, respectively. Treatment of human foreskin fibroblasts with simvastatin or with liposome-encapsulated pravastatin resulted in decreased expression of transcript encoding CTGF. Overall, our novel statin formulations encapsulated in liposomes were successfully delivered through topical application, significantly reducing hypertrophic scarring in a rabbit ear model.


Assuntos
Cicatriz Hipertrófica/metabolismo , Fibroblastos/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Pele/metabolismo , Animais , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/prevenção & controle , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo III/efeitos dos fármacos , Colágeno Tipo III/genética , Fator de Crescimento do Tecido Conjuntivo/efeitos dos fármacos , Fator de Crescimento do Tecido Conjuntivo/genética , Orelha Externa/lesões , Orelha Externa/metabolismo , Orelha Externa/patologia , Eritema , Fibroblastos/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Técnicas In Vitro , Lipossomos , Melaninas , Molécula-1 de Adesão Celular Endotelial a Plaquetas/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pravastatina/administração & dosagem , Pravastatina/farmacologia , Coelhos , Sinvastatina/administração & dosagem , Sinvastatina/farmacologia , Pele/lesões , Pele/patologia , Espectrofotometria
2.
Int J Nanomedicine ; 13: 6699-6715, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425484

RESUMO

BACKGROUND: Influenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses. METHODS: In the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model. Furthermore, we used monosodium urate (MSU) crystals as an adjuvant and co-administered the vaccine formulation as an intranasal mist to flu-free nursery pigs, twice at 3-week intervals. RESULTS: Liposome peptides flu vaccine delivered with MSU adjuvant improved the hemagglutination inhibition antibody titer and mucosal IgA response against the SwIAV challenge and also against two other highly genetically variant IAVs. Liposomal vaccines also enhanced the frequency of peptides and virus-specific T-helper/memory cells and IFN-γ response. The improved specific cellular and mucosal humoral immune responses in adjuvanted liposomal peptides flu vaccine partially protected pigs from flu-induced fever and pneumonic lesions, and reduced the nasal virus shedding and viral load in the lungs. CONCLUSION: Overall, our study shows great promise for using liposome and MSU adjuvant- based subunit flu vaccine through the intranasal route, and provides scope for future, pre-clinical investigations in a pig model for developing potent human intranasal subunit flu vaccines.


Assuntos
Adjuvantes Imunológicos/farmacologia , Imunidade , Vacinas contra Influenza/imunologia , Nanopartículas/química , Infecções por Orthomyxoviridae/imunologia , Peptídeos/imunologia , Ácido Úrico/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Sequência de Aminoácidos , Animais , Formação de Anticorpos/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Citocinas/biossíntese , Cães , Imunidade/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1 , Lipossomos , Pulmão/patologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Nanopartículas/ultraestrutura , Infecções por Orthomyxoviridae/virologia , Peptídeos/química , Sus scrofa , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Vacinação , Carga Viral/efeitos dos fármacos
3.
J Korean Assoc Oral Maxillofac Surg ; 40(2): 50-60, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24868501

RESUMO

Tooth loss is very a very common problem; therefore, the use of dental implants is also a common practice. Although research on dental implant designs, materials and techniques has increased in the past few years and is expected to expand in the future, there is still a lot of work involved in the use of better biomaterials, implant design, surface modification and functionalization of surfaces to improve the long-term outcomes of the treatment. This paper provides a brief history and evolution of dental implants. It also describes the types of implants that have been developed, and the parameters that are presently used in the design of dental implants. Finally, it describes the trends that are employed to improve dental implant surfaces, and current technologies used for the analysis and design of the implants.

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