Methylene blue-loaded flexible liposomes improve the efficacy of photodynamic therapy for the treatment of bacterial keratitis

被引：0

作者：

Villanueva-Martinez, Angelica ^{[1
]}

Molina-Alejandre, Omar ^{[1
]}

Flores-Perez, Alegre ^{[1
]}

Nava-Arzaluz, Maria Guadalupe ^{[1
]}

Lopez-Mera, Gonzalo Hedain ^{[2
]}

Cruz-Morales, Raul Dali ^{[2
]}

Sanchez-Garcia, Diego ^{[2
]}

Becerril-Osnaya, Andrea ^{[3
]}

Perez-Carranza, Abril ^{[3
]}

Pinon-Segundo, Elizabeth ^{[4
]}

Bernal-Chavez, Sergio ^{[5
]}

Pedraza-Chaverri, Jose ^{[6
]}

Medina-Campos, Omar Noel ^{[6
]}

del Valle-Perez, Paulina ^{[7
]}

Cerecedo, Doris ^{[8
]}

Martinez-Vieyra, Ivette ^{[8
]}

Ganem-Rondero, Adriana ^{[1
]}

机构：

[1] Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan, Lab Invest & Posgrad Tecnol Farmaceut L 322, Ave 1 Mayo S-N, Cuautitlan 54740, Estado De Mexic, Mexico

[2] Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan, Engn Dept, Carr Cuautitlan Teoloyucan Km 2 5, Cuautitlan 54714, Edo De Mex, Mexico

[3] Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan, Serv Diagnost Bacteriol Poblac Interna & Externa F, Ave 1 Mayo S-N, Cuautitlan 54740, Estado De Mexic, Mexico

[4] Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan, Lab Sistemas Farmaceut Liberac Modificada, Carr Cuautitlan Teoloyucan Km 2 5, Cuautitlan 54714, Edo De Mex, Mexico

[5] Univ Las Amer Puebla, Dept Ciencias Quim Biol, Cholula 72820, Puebla, Mexico

[6] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City, Mexico

[7] Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City, Mexico

[8] Inst Politecn Nacl, Escuela Nacl Med y Homeopatia, Secc Estudios Posgrad, Lab Hematobiol, Mexico City, Mexico

来源：

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY | 2025年 / 108卷

关键词：

Mexico; Methylene blue; Liposomes; Keratitis; Photodynamic therapy; Drug-resistant bacteria; VESICLES; DELIVERY;

D O I：

10.1016/j.jddst.2025.106906

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Photodynamic therapy is emerging as a promising alternative to combat antibiotic-resistant microorganisms causing keratitis. Since photosensitizer penetration through bacterial cell walls limits efficacy, nanovesicles offer a viable solution to enhance effectiveness. This study evaluated the antimicrobial efficacy of flexible liposomes loaded with methylene blue against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa. Liposomes were prepared using the film hydration method, optimizing lecithin type, solvent, and edge activator. The antimicrobial activity of the liposomal systems was assessed using two methylene blue concentrations and two light energy fluences. Incorporating methylene blue into the liposomes enhanced the growth inhibition of MRSA compared to free methylene blue. For P. aeruginosa, significant increases in growth inhibition were observed with higher irradiance, application time, and methylene blue concentration in liposomes compared to the photosensitizer solution (free form). Reactive oxygen species production after photoactivation was quantified by fluorescein photobleaching, showing a significant increase with the liposomal system compared to free methylene blue. Although reactive oxygen species production reached saturation at higher methylene blue concentrations, bacterial growth inhibition continued to increase with prolonged exposure, suggesting accumulated oxidative damage. Cell viability studies with HaCaT cells indicated that at 20 mW/cm2, diluted samples (1:100 and 1:50) were non-cytotoxic, while a 1:10 dilution (20 mu g/mL) significantly reduced viability. All samples were cytotoxic at 60 mW/cm2, likely due to their strong membrane affinity. These findings highlight the need for optimized photodynamic therapy conditions to balance antimicrobial efficacy with host cell safety.

引用

页数：13