RESUMEN
AIM: To develop a nanocarrier for targeted delivery of agents to the cartilage. MATERIALS & METHODS: Chondrocyte affinity peptide modified PEGylated polyamidoamine conjugates (CAP-PEG-PAMAM) were prepared and rhodamine B isothiocyanate (RB) fluorophore was linked on them for comparative biological tracing and profiling. RESULTS: CAP4-PP-RB exhibited much more efficient cellular uptake in vitro than that of PEG-PAMAM-RB. Both the conjugates were likely internalized by chondrocytes via clathrin and caveolin co-mediated endocytosis, and delivered to lysosomes. In vivo imaging demonstrated the fluorescein-labeled nanocarrier was capable to persist in the joint cavity of rats for a prolonged time. Furthermore, the CAP4-PEG-PAMAM showed a good biocompatibility and enhanced penetration effects in vivo. CONCLUSION: CAP-PEG-PAMAM could be an effective nanocarrier for intra-articular delivery of agents to cartilage.
Asunto(s)
Dendrímeros/administración & dosificación , Portadores de Fármacos/administración & dosificación , Articulaciones/efectos de los fármacos , Nanopartículas/administración & dosificación , Péptidos/administración & dosificación , Polietilenglicoles/administración & dosificación , Animales , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Cartílago/efectos de los fármacos , Caveolina 1/química , Condrocitos/efectos de los fármacos , Clatrina/química , Dendrímeros/química , Portadores de Fármacos/química , Endocitosis/efectos de los fármacos , Humanos , Articulaciones/patología , Lisosomas/efectos de los fármacos , Masculino , Nanopartículas/química , Péptidos/química , Polietilenglicoles/química , Ratas , Rodaminas/administración & dosificación , Rodaminas/químicaRESUMEN
Partly PEGylated polyamidoamine (PAMAM) dendrimer was used as the nanocarrier for the cytoplasmic delivery of kartogenin (KGN) to induce chondrogenic differentiation of mesenchymal stem cells (MSCs). Here, KGN was conjugated to the surface of PAMAM and the end group of polyethylene glycol (PEG) to obtain PEG-PAMAM-KGN (PPK) and KGN-PEG-PAMAM (KPP) conjugate, respectively. The effects of PPK and KPP on the in vitro chondrogenic differentiation of MSCs were evaluated. KPP induced higher expression of chondrogenic markers than PPK and free KGN. In particular, after treatment of KPP, CBF ß nuclear localization intensity was significantly increased, indicating enhanced efficacy of chondrogenesis. The fluorescein labeled PEG-PAMAM was capable to persist in the joint cavity for a prolonged time of both healthy and osteoarthritis (OA) rats. Thus, PEG-PAMAM could be a useful nanocarrier for intra-articular (IA) delivery of drug to treat OA.
Asunto(s)
Anilidas/administración & dosificación , Condrogénesis/efectos de los fármacos , Dendrímeros/química , Portadores de Fármacos/química , Células Madre Mesenquimatosas/efectos de los fármacos , Ácidos Ftálicos/administración & dosificación , Polietilenglicoles/química , Anilidas/farmacocinética , Anilidas/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Células Madre Mesenquimatosas/citología , Osteoartritis/tratamiento farmacológico , Ácidos Ftálicos/farmacocinética , Ácidos Ftálicos/farmacología , RatasRESUMEN
This work aims to explore the application value and clinical efficacy of laparoscopic enterolysis surgery for the treatment of adhesive intestinal obstruction. A total of 126 inpatient cases of intestinal adhesion were selected. In order to observe the effects and complications of surgery, the patients were randomly assigned into laparoscopic and laparotomy groups, with 63 cases in each group. The operative time, blood loss, postoperative ambulation time, exhaustion time, postoperative analgesia number of patients, and hospital days of the patients in the laparoscopic group were compared with those in the control group, and the differences were all statistically significant (p < 0.05). In the laparoscopy group, two patients experienced rupture of the small intestine during the surgery, but recovered well after endoscopic suture repair, although there was one case of postoperative pulmonary infection. The difference was statistically significant in the laparotomy group of patients, with one case of intestinal fistula, two cases of surgical wound infection, one case of incisional hernia, three cases of postoperative pulmonary infection, and one case of urinary tract infection. Compared with laparotomy, laparoscopic enterolysis surgery has shorter operative time, less blood loss, faster postoperative recovery, and fewer complications.