RESUMO
An intelligent drug delivery platform based on the hybrids of mesoporous silica nanoparticles (MSN), sodium hyaluronate (HA), chitosan (CS) and oxidized sodium carboxymethyl cellulose (oxCMC) is developed, which can be used for dual-responsive dual-drug delivery. Hydrophilic cytarabine (Cyt) is first loaded into the mesopores of the aminated MSN (NH2-MSN), which is encapsulated by the hydrogel of HA and cystamine (Cys) crosslinked via amidation. The Cyt encapsulated hydrogel which is denoted as Cyt/NH2-MSN/HA is co-encapsulated with hydrophobic methotrexate (MTX) into the hydrogel of CS and oxCMC resulted from Schiff base reaction. Since the acylhydrazone bonds (-HC=N-) between CS and oxCMC are sensitive to pH and the disulfide bonds (-S-S-) in Cys are sensitive to glutathione (GSH), the resultant dual-drug encapsulated hydrogel, denoted as Cyt/NH2-MSN/HA/MTX/CS/oxCMC, can be used for dual-responsive (pH and GSH) drug delivery. The results of cell viability demonstrate that the developed dual-drug encapsulated hydrogel has significantly higher efficacy of chemotherapy than that of single-drug (MTX or Cyt) encapsulated hydrogel.
Assuntos
Quitosana , Nanopartículas , Carboximetilcelulose Sódica , Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Concentração de Íons de Hidrogênio , Nanopartículas/química , Porosidade , Dióxido de Silício/química , SódioRESUMO
To improve the efficacy of chemotherapy and relieve the pain associated with colorectal cancer, a dual-drug delivery system (DDDS) is proposed. In this system, methotrexate (MTX) loaded CaCO3 (CaCO3/MTX) and aspirin (Asp) are co-entrapped in the hydrogels of alginate (Alg) and sodium carboxymethyl cellulose (CMC) crosslinked with Ca2+. The hydrogels can protect the anti-cancer drug of MTX from being absorbed in stomach and small intestine and ensure their efficacy at the target site of colorectum. More importantly, dual pH-responsive drug delivery can be achieved by the DDDS. Because the pH varies at small intestine and colorectum of human body, dual pH-responsive delivery of Asp and MTX can be achieved at the two organs, respectively, in response to ambient pH. These finding are of significant importance for medical science and pharmaceutics.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos/química , Hidrogéis/química , Metotrexato/farmacologia , Alginatos/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/química , Aspirina/química , Aspirina/farmacologia , Carbonato de Cálcio/química , Carboximetilcelulose Sódica/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Metotrexato/químicaRESUMO
Graphene quantum dots (GQDs) were prepared by the pyrolysis of citric acid (CA), which were used for the loading of hydrophilic cytarabine (Cyt), an anti-cancer drug, and then wrapped with chitosan (CS) gels for the encapsulation of the loaded Cyt. The fluorescent stability of GQDs was significantly enhanced in the presence of CS, which might be attributed to the inhibited agglomeration of GQDs by the CS gels. In addition, the burst release of Cyt from the developed carrier was also effectively relieved by the CS coating. Since the incorporation of Cyt into GQDs was achieved by amidation reaction, the delivery of Cyt from the carrier was pH-sensitive due to the hydrolysis of the amido linkage between GQDs and Cyt in acidic medium.
