Therapeutic Effect Of Dual-Drug Delivery System Based On Emulsion Electrospun Membrane Against Abdominal Diseases

ObjectiveWith the rapid development of nanotechnology,nano-drug delivery system has attracted more and more attentions in the diagnosis and treatment process of many diseases.For common abdominal diseases,such as abdominal injuries and abdominal organ cancer,surgeries are still the mainstream treatment method in clinic.However,surgical processes often lead to postoperative inflammatory response and fibrin deposition,which can result in the formation of peritoneal adhesion.In addition,for the treatment of abdominal cancer,surgical resection followed by traditional systematical radiotherapy and chemotherapy is always inclined to cause serious damages to normal organs.Moreover,such treatment methods require multiple administrations which are very cumbersome.In order to solve the above problems during the treatment process of abdominal diseases,we developed a dual-drug delivery system based on emulsion electrospun membrane to inhibit abdominal adhesion,prevent primary and advanced liver cancer,and provide effective options for new clinical treatment methods.MethodsIn our study,we developed two kinds of membranes based on emulsion electrospinning:(1)The m PEG-b-PLGA emulsion electrospun nanofibers loaded with diclofenac sodium(DS)in the core and 10-hydroxycamptothecin(HCPT)in the sheath.Furthermore,ultraviolet-ozone(UVO)treatment was applied to improve the bio-adhesion ability of membrane.(2)The m PEG-b-PLGA emulsion electrospun nanofibers loaded with tea polyphenols(TP)in the core and 10-hydroxycamptothecin(HCPT)in the sheath.Basic characterizations,degradation properties,and drug delivery profiles of membranes were performed in vitro.Meanwhile,three kinds of animal models were performed to assess the treatment efficacy of the emulsion electrospun membranes in abdominal diseases.(1)Mice cecum-abdomen peritoneal adhesion animal model was established.Gross evaluation,adhesion grades,adhesion area,and pathological and immunofluorescent analyses were used to analyze the adhesion prevention effect of m PEG-b-PLGA-DS-HCPT emulsion electrospun membrane.(2)Mice primary hepatoma model was applied.Gross observation of liver,organ coefficients,blood biochemical values,pathology,immunofluorescence and Western blot analyses were performed to evaluate the treatment efficacy of the m PEG-b-PLGA-TP-HCPT emulsion electrospun membrane against primary liver cancer.(3)Mice advanced hepatoma model was used.Gross observation,organ coefficients,blood biochemical values,abdominal circumference,ascites volume,the cell number and viability of ascites,pathology,immunofluorescence and Western blot analyses were performed to evaluate the treatment efficacy of the m PEG-b-PLGA-TP-HCPT emulsion electrospun membrane against advanced liver cancer.ResultsMembrane characterization results indicated that the electrospun fibers were smooth and evenly distributed and there were no obvious drug crystals on the surface of the membrane.The emulsion electrospun fibers possessed specific core/sheath structures with hydrophilic drug in the core and hydrophobic drug in the sheath.The drugs could be released sustainably from the designed drug delivery system and there were no obvious burst release profiles.In addition,the membrane was biocompatible and could be degraded in vivo without serious inflammatory response.The animal studies indicated that the m PEG-b-PLGA-DS-HCPT emulsion electrospun membrane possessed increased bio-adhesion ability and could well prevent the formation of peritoneal adhesion through inhibiting the fibrin deposition and the formation of tumor necrosis factor-?(TNF-?),interleukin-1(IL-1),and interleukin-6(IL-6).Furthermore,the m PEG-b-PLGA-TP-HCPT emulsion electrospun membrane could inhibit the expression of reactive oxygen species modulator 1(ROMO1)and proliferating cell nuclear antigen(PCNA)and increase the expression of caspase-3,thus leading to the apoptosis of tumor cells and further decreasing their invasiveness and metastatic abilities.Moreover,this drug delivery system was safe with no damage to other organs.The m PEG-b-PLGA-TP-HCPT emulsion electrospun membrane could inhibit the development of orthotopic liver cancer and reduce the generation of cancerous ascites and the viability of ascites tumor cells in mice.ConclusionOwing to the core/sheath structure,the emulsion electrospun membrane can carry drugs with different solubility and control the sustained release of these drugs.Our study demonstrated the efficacy of rationally-designed membrane in the treatment of peritoneal adhesion and primary and advanced hepatomas.This dual-drug delivery system possesses wide application prospects and provides new strategies to solve the problems in the treatment of abdominal diseases.