Enhanced Oral NO Delivery through Bioinorganic Engineering of Acid-Sensitive Prodrug into a Transformer-like DNIC@MOF Microrod.

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2(µ-SCH2CH2COOH)2(NO)4] (DNIC-2) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2, oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

The use of injectable spherically symmetric cell aggregates self-assembled in a thermo-responsive hydrogel for enhanced cell transplantation.

Typical cell transplantation techniques involve the administration of dissociated cells directly injected into muscular tissues; however, retention of the transplanted cells at the sites of the cell graft is frequently limited. An approach, using spherically symmetric aggregates of cells with a relatively uniform size self-assembled in a thermo-responsive methylcellulose hydrogel system, is reported in the study. The obtained cell aggregates preserved their endogenous extracellular matrices (ECM) and intercellular junctions because no proteolytic enzyme was used when harvesting the cell aggregates. Most of the cells within aggregates (with a radius of approximately 100 microm) were viable as indicated by the live/dead staining assay. After injection through a needle, the cell aggregates remained intact and the cells retained their activity upon transferring to another growth surface. The cell aggregates obtained under sterile conditions were transplanted into the skeletal muscle of rats via local injection. The dissociated cells were used as a control. It was found that the cell aggregates can provide an adequate physical size to entrap into the muscular interstices and offer a favorable ECM environment to enhance retention of the transplanted cells at the sites of the cell graft. These results indicated that the spherically symmetric cell aggregates developed in the study may serve as a cell delivery vehicle for therapeutic applications.

A novel technique to apply a Seprafilm (hyaluronate-carboxymethylcellulose) barrier following laparoscopic surgeries.

OBJECTIVE: To describe a novel technique for application of a Seprafilm (modified hyaluronate-carboxymethylcellulose) barrier laparoscopically, and to assess the adequacy of coverage of desired sites. DESIGN: Retrospective cohort study. SETTING: University tertiary hospital. PATIENT(S): One hundred twenty-seven patients who underwent fertility-sparing laparoscopic surgery. INTERVENTION(S): The Seprafilm was rolled up in a plastic package, then delivered through the main trocar. It was unrolled and positioned to cover the traumatized surface of the uterus, ovaries, and tubes. During application, the pelvis was photographed, videotaped, and the pictures were reviewed by two surgeons. MAIN OUTCOME MEASURE(S): The adequacy of the application was divided into three levels as to whether the Seprafilm could cover all the traumatized surfaces. RESULTS: Of the first 15 patients, 4 of 15 (26%) had successful coverage of the traumatized surface with the first sheet of Seprafilm. Of the following 112 patients, 97 of 112 (86.5%) had successful coverage with the first sheet. The success rate climbed to 96% after the second or third sheet. The average time for the application of six pieces (one sheet cut into six pieces) was 21 +/- 4 minutes. The posterior cul-de-sac is difficult to apply well. CONCLUSION(S): It is feasible to apply the antiadhesion barrier Seprafilm laparoscopically. Further studies will be needed to assess the efficacy of reducing adhesion following such use.