RESUMO
Eradicating subcutaneous bacterial infections remains a significant challenge. This work reports an injectable system of hollow microspheres (HMs) that can rapidly produce localized heat activated by near-infrared (NIR) light and control the release of an antibiotic via a "molecular switch" in their polymer shells, as a combination strategy for treating subcutaneous abscesses. The HMs have a shell of poly(d,l-lactic-co-glycolic acid) (PLGA) and an aqueous core that is comprised of vancomycin (Van) and polypyrrole nanoparticles (PPy NPs), which are photothermal agents. Experimental results demonstrate that the micro-HMs ensure efficiently the spatial stabilization of their encapsulated Van and PPy NPs at the injection site in mice with subcutaneous abscesses. Without NIR irradiation, the HMs elute a negligible drug concentration, but release substantially more when exposed to NIR light, suggesting that this system is suitable as a photothermally-responsive drug delivery system. The combination of photothermally-induced hyperthermia and antibiotic therapy with HMs increases cytotoxicity for bacteria in abscesses, to an extent that is greater than the sum of the two treatments alone, demonstrating a synergistic effect. This treatment platform may find other clinical applications, especially for localized hyperthermia-based cancer therapy.
Assuntos
Abscesso/terapia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Sistemas de Liberação de Medicamentos , Dermatopatias/terapia , Abscesso/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Temperatura Alta , Raios Infravermelhos , Injeções Subcutâneas , Ácido Láctico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Microesferas , Nanopartículas , Fotoquímica , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pirróis , Dermatopatias/tratamento farmacológico , Distribuição Tecidual , Vancomicina/administração & dosagem , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Cicatrização/efeitos dos fármacosRESUMO
Treating inflammation with a dual-switch-controlled release system: The release of a drug from the developed microbead system occurs only in response to both an increase in local temperature and an acidic environmental pH. This dual-switch-controlled release system has the advantages of distinguishing between inflamed and healthy tissues to improve treatment efficacy.
Assuntos
Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Microesferas , Microscopia Confocal , Microscopia Eletrônica de VarreduraRESUMO
Noroviruses (NV) are +ssRNA viruses responsible for severe gastroenteritis; no effective vaccines/antivirals are currently available. We previously identified Suramin (9) as a potent inhibitor of NV-RNA dependent RNA polymerase (NV-RdRp). Despite significant in vitro activities versus several pharmacological targets, Suramin clinical use is hampered by pharmacokinetics/toxicity problems. To improve Suramin access to NV-RdRp in vivo, a Suramin-derivative, 8, devoid of two sulphonate groups, was synthesized, achieving significant anti-human-NV-RdRp activity (IC50â=â28 nM); the compound inhibits also murine NV (mNV) RdRp. The synthesis process led to the isolation/characterization of lower molecular weight intermediates (3-7) hosting only one sulphonate head. The crystal structures of both hNV/mNV-RdRps in complex with 6, were analyzed, providing new knowledge on the interactions that a small fragment can establish with NV-RdRps, and establishing a platform for structure-guided optimization of potency, selectivity and drugability.
Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Norovirus/enzimologia , RNA Polimerase Dependente de RNA/antagonistas & inibidores , Suramina/química , Suramina/farmacologia , Animais , Cristalografia por Raios X , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Peso Molecular , Conformação Proteica , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/metabolismo , Relação Estrutura-Atividade , Ácidos Sulfônicos/síntese química , Ácidos Sulfônicos/química , Ácidos Sulfônicos/metabolismo , Ácidos Sulfônicos/farmacologia , Suramina/síntese química , Suramina/metabolismo , Ureia/síntese química , Ureia/química , Ureia/metabolismo , Ureia/farmacologiaRESUMO
This work presents a novel approach for labeling hippuric acid with I-131 using microwaves. It utilizes copper(II) acetate as a catalyst of the labeling. The process involves the use of this catalytic copper(II) acetate at low dilutions that were nevertheless sufficient to produce labeled hippuric acid with high radiochemical purity in a short time. Therefore, the novel technique overcomes the limitations of previously reported conventional methods that involve heating.
Assuntos
Radioisótopos do Iodo/química , Ácido Iodoipúrico/química , Micro-Ondas , Compostos Organometálicos/química , Compostos Radiofarmacêuticos/síntese química , Catálise , Marcação por Isótopo/métodosRESUMO
A facile preparation of arylmethyl and heteroarylmethyl phosphonate esters was achieved involving a Lewis acid mediated Michaelis-Arbuzov reaction at room temperature. Interaction of arylmethyl halides/alcohols with triethyl phosphite in the presence of Lewis acid at room temperature afforded phosphonate esters in good yields.
Assuntos
Ácidos de Lewis/química , Organofosfonatos/síntese química , Ésteres , Estrutura Molecular , Organofosfonatos/química , TemperaturaRESUMO
In the title compound, C(20)H(19)NO(6)S, the phenyl ring of the phenyl-sulfonyl group makes a dihedral angle of 83.35â (5)° with the indole ring system. The mol-ecular structure exhibits a number of short intramolecular C-Hâ¯O contacts.
RESUMO
In the title compound, C(24)H(25)NO(8)S, the indole unit is planar and makes a dihedral angle of 79.73â (11)° with the phenyl ring of the sulfonyl substituent. The mol-ecules in the unit cell are stabilized by C-Hâ¯O and C-Hâ¯π inter-molecular inter-actions in addition to van der Waals forces.
RESUMO
In the title compound, C(26)H(25)NO(6)S, the phenyl ring forms a dihedral angle of 82.5â (1)° with the indole ring system. The mol-ecular structure is stabilized by weak intra-molecular C-Hâ¯O inter-actions and the crystal structure is stabilized by weak inter-molecular C-Hâ¯O inter-actions.
RESUMO
In the title compound, C(19)H(18)BrNO(5)S, the plane of the phenyl ring forms a dihedral angle of 76.99â (6)° with the indole ring system. The Br atom is disordered over two positions, with site-occupancy factors of 0.833â (14) and 0.167â (14). The mol-ecular structure is stabilized by weak intra-molecular C-Hâ¯O inter-actions and the crystal packing is stabilized by weak inter-molecular C-Hâ¯O inter-actions.
RESUMO
In the title mol-ecule, C(15)H(12)BrNO(2)S, the indole mean plane and phenyl ring are nearly orthogonal to each other, forming a dihedral angle of 88.19â (13)°. The Br atom is disordered over two close positions with occupancies of 0.56â (4) and 0.44â (4). The crystal packing exhibits weak inter-molecular C-Hâ¯π inter-actions.