RESUMEN
The study explores anticancer potential of telmisartan (TS) loaded lipid nanocarriers (TLNs) in glioma cells as a potential repurposing nanomodality along with estimation of drug availability at rat brain. Experimental TLNs were produced by previously reported method and characterized.In vitroanticancer efficacy of experimental TLNs was estimated by MTT, confocal microscopy, and FACs analysis in glioma cells. Plasma and brain pharmacokinetic (PK) parameters were also analysed by LCMS/MS. Spherical, nanosized, homogenous, unilamellar, TLNs were reported having desirable drug loading (9.5% ± 0.6%), negative zeta potential and sustained TS release tendency. FITC-TLNs were sufficiently internalized into U87MG cells line within 0.5 h incubation period. IC50for TLNs was considerably higher than free TS in the tested glioma cell lines. Further, TLNs induced superior apoptotic effect in U87MG cells than TS. PK (plasma/brain) data depicted higher AUC,Vss, MRT with lower Cltfor TLNs suggesting improved bioavailability,in vivoresidence and sustained drug availability than free TS administration. Docking studies rationalizedin vitro/in vivoresults as preferably higher binding affinity (docking score:12.4) was detected for TS with glioma proteins. Further,in vivostudies in glioma bearing xenograft model is underway for futuristic clinical validation of TLNs.
Asunto(s)
Apoptosis , Portadores de Fármacos , Glioma , Lípidos , Nanopartículas , Telmisartán , Telmisartán/farmacocinética , Telmisartán/farmacología , Telmisartán/química , Telmisartán/administración & dosificación , Glioma/tratamiento farmacológico , Glioma/patología , Glioma/metabolismo , Humanos , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ratas , Nanopartículas/química , Lípidos/química , Simulación del Acoplamiento Molecular , Reposicionamiento de Medicamentos , Masculino , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Liberación de FármacosRESUMEN
AIM: The work reports a novel nanophytosomal gel encapsulating Alpinia galanga (L.) Willd leaf essential oil to treat periodontal infections. METHODS: Alpinia oil-loaded nanophytosomes (ANPs) were formulated by lipid layer hydration technique and were evaluated by FESEM, cryo-TEM, loading efficiency, zeta potential, particle size, release profile etc. Selected ANPs-loaded gel (ANPsG) was evaluated by both in vitro and in vivo methods. RESULTS: Selected ANPs were spherical, unilamellar, 49.32 ± 2.1 nm size, 0.45 PDI, -46.7 ± 0.8 mV zeta potential, 9.8 ± 0.5% (w/w) loading, 86.4 ± 3.02% (w/w) loading efficiency with sustained release profile. ANPsG showed good spreadability (6.8 ± 0.3 gm.cm/sec), extrudability (79.33 ± 1.5%), viscosity (36522 ± 0.82 cps), mucoadhesive strength (44.56 ± 3.5 gf) with sustained ex vivo release tendency. Satisfied ZOI and MIC was observed for ANPsG against periodontal bacteria vs. standard/control. ANPsG efficiently treated infection in ligature induced periodontitis model. Key pharmacokinetic parameters like AUC, MRT, Vd were enhanced for ANPsG. CONCLUSION: ANPsG may be investigated for futuristic clinical studies.
Asunto(s)
Alpinia , Geles , Aceites Volátiles , Hojas de la Planta , Aceites Volátiles/química , Aceites Volátiles/administración & dosificación , Aceites Volátiles/farmacocinética , Aceites Volátiles/farmacología , Alpinia/química , Animales , Geles/química , Hojas de la Planta/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Enfermedades Periodontales/tratamiento farmacológico , Masculino , Nanopartículas/química , Ratas , Periodontitis/tratamiento farmacológico , Simulación por ComputadorRESUMEN
Coming to the edge of disease manufacturing in the twenty-first-century, breast cancer occupies a terrifying scenario in the globe, especially in adult women. Its curiosity endeavours remarkable advances made during the past decennaries for cancer treatment and diagnosis.
It accounts for the fifth leading cause of transience, killing approximately 570,000 people per annum. To reduce the prognosis of clinical oncological development with the application of a new chemical entity, some of the critical challenges, like active pharmaceutical ingredients with high chemical resistance, extreme side effects, and high treatment costs are some of the limitations in the curbing aspects of breast melanoma. In cancer research, hence, the development of drugs that are safe, efficient, and cost-effective remains a 'Holy Grail' that may be considered as a boon to target the malignant tissues with novel therapeutics devices. Through the findings on overcoming the drawbacks of traditional methods, researchers have given special attention to cancer-preventive and theranostic approaches based on some novel drug delivery systems. The present study forecasts the wide-ranging modern applications, and on developing some novel liposomal drug delivery therapy against breast cancer.