ABSTRACT
BACKGROUND/AIMS: This study investigated the protection provided by gabexate mesylate thermo-sensitive in-situ gel (GMTI) against grade III pancreatic trauma in rats. METHODS: A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: Ascites, serum amylase, lipase, CRP, IL-6, and TNF-α levels were significantly increased in the pancreas trauma (PT) groups with prolonged trauma time and were significantly decreased after GMTI treatment. The morphological structure of the pancreas was loose, the acinus was significantly damaged, the nuclei were irregular and hyperchromatic, and there was inflammatory cell invasion in the PT group compared to the control. After GMTI treatment, the morphological structure of the pancreas was restored, and the damaged acinus and inflammatory cell invasion were decreased compared to the PT group. Moreover, the cell apoptosis index was significantly increased in the PT group and restored to the same levels as the control group after GMTI treatment. CONCLUSIONS: GMTI, a novel formulation and drug delivery method, exhibited specific effective protection against PT with acute pancreatitis therapy and has potential value as a minimally invasive adjuvant therapy for PT with acute pancreatitis.
Subject(s)
Animals , Rats , Amylases , Apoptosis , Ascites , C-Reactive Protein , DNA Nucleotidylexotransferase , Eosine Yellowish-(YS) , Gabexate , Hematoxylin , Interleukin-6 , Lipase , Methods , Necrosis , Pancreas , Pancreatic Ducts , PancreatitisABSTRACT
Objective To investigate the tumor inhibition effect of paclitaxel long-circulating thermo sensitive liposomes (PLTL) in mice bearing Lewis lung carcinoma cells. Methods A tumor-bearing mouse model was established, and the mice were randomly divided into five groups: control, heating, paclitaxel (PTX), paclitaxel thermo sensitive liposomes (PTL), and PLTL groups. The living status was observed in the mice. The volume and weight of the tumor were measured. The morphological changes in the tumor cells were observed f by HE staining and apoptosis of the tumor cells was determined by flow cytometry. Results The inhibition rate of tumor in PTX, PTL and PLTL groups was 48.87%, 57.22%and 78.87%, respectively. The apoptotic rate of tumor cell in PTX, PTL and PLTL groups was (42.7 ± 3 .8)%, (54.6 ± 2.9)%and (69.7 ± 5.0)%, respectively. Conclusions PLTL, as compared with PTX and PTL, has an evident thermo sensitive feature and increases the anticancer effect of paclitaxel remarkably in combination with local hyperthermia.
ABSTRACT
BACKGROUND: Polymer micelles is a new type of drug carriers developed in recent years,with a wide range of carrying drugs,structural stability,excellent tissue permeability,long residence of drugs in vivo,and effective reaching the target.The performances of intelligent targeting and decreasing the initial burst release have become the focus of recent researches.OBJECTIVE: To obtain an intelligent targeting drug carrier of low critical solution temperature(LCST)at 40℃,to change drug release behavior through the changes of temperature,and to further improve the stability and drug release behavior of the micelles by core-crosslinking.METHODS: By radical polymerization of N-isopropylacrylamide(NIPAAm)and N,N-dimethylacrylamide(DMAAm),hydroxyl terminated poly(N-isopropylacrylamide-co-N,N-dimethyl acrylamide)[P(NIPAAm-co-DMAAm)]was synthesized.Molecular weight and LCST of P(NIPAAm-co-DMAAm)were regulated by adjusting the mercaptoethanol and monomer ratio,as well as the ratio of NIPAAm and DMAAm,Amphiphilic block copolymer P(NIPAAm-CO-DMAAm)-b-PCL was prepared via bulk ring-opening polymerization of ε-caprolactone by using the end hydroxyl group of P(NIPAAm-co-DMAAm)as initiator and stannous octoate as catalyst.The block copolymer reacted with acryloyl chloride to obtain amphiphilic block copolymers with unsaturated double bonds at the terminal.Drug loaded nano-micelles with different nuclear cross-linked degrees were prepared by dialysis method,and its release behavior was investigated.RESULTS AND CONCLUSION: Amphiphilic block copolymers,with the LCST of 42℃,were obtained with hydroxyl or acryloyl endgroup.By blending them at different ratios,thermo-sensitive drug-loaded nano-micelles with different core-cresslinking degrees were prepared.The drug release rate was faster at 43℃ than at 37℃.With the core-crosslinking degrees increasing,the release of paclitaxel gradually slowed.The results suggest that the drug release rate from micelles prepared from thermo-sensitive P(NIPAAm-co-DMAAm)-b-PCL can be regulated by the degree of cross-linking.