Oxytocin Versus Oral Misoprostol for Induction of Labor in Pregnant Women with Term Prelabor Rupture of Membranes: a Randomized Clinical Trial.

This study compares the effectiveness and safety of oxytocin infusion against oral misoprostol for inducing labour in pregnant women with term prelabor membrane rupture. We randomized 173 pregnant women presenting with term prelabor rupture of membranes (PROM) at Ain Shams University Maternity Hospital into Group A (underwent induction of labor (IOL) by 25µg misoprostol oral tablet every 4 h, for maximum 5 doses) and an identical Group B: (underwent IOL by oxytocin infusion according to the hospital protocol). Our primary outcome was rate of vaginal delivery within 24 h, while the secondary outcomes included the time till active phase, induction to delivery interval, maternal pyrexia, nausea and vomiting, fetal distress, Apgar score, birth weight, and neonatal intensive care unit admission. Both groups showed high rates of vaginal delivery (82.4% & 87.1% for misoprostol group and oxytocin group respectively) with no significant difference between the two groups (p=0.394). However, patients induced by misoprostol took significantly less time to reach active phase with a shorter induction to delivery interval as compared to patients induced with oxytocin. This difference was clear in multiparous women, but not observed in primiparous women when subgroup analysis was done. No significant difference was found as regards other outcomes. Our study showed that both oral misoprostol and oxytocin are effective and safe for IOL in patients with PROM, with shorter induction-delivery interval in patients induced by oral misoprostol, an effect that is clear in multiparous but not primiparous women. TRIAL REGISTRATION: NCT05215873, on 31/01/2022, "retrospectively registered".

Nanoparticle Fraught Liposomes: A Platform for Increased Antibiotic Selectivity in Multidrug Resistant Bacteria.

Increasing antibiotic concentrations within bacterial cells while reducing them in mammalian ones would ultimately result in an enhancement of antibacterial actions, overcoming multidrug resistance, all while minimizing toxicity. Nanoparticles (NPs) have been used in numerous occasions to overcome antibiotic resistance, poor drug solubility, and stability. However, the concomitant increase in antibiotic concentration in mammalian cells and the resultant toxicity are usually overlooked. Without compromising bacterial cell fusion, large liposomes (Lip) have been reported to show reduced uptake in mammalian cells. Therefore, in this work, small NP fraught liposomes (NP-Lip) were formulated with the aim of increasing NP uptake and antibiotic delivery in bacterial cells but not in mammalian ones. Small polylactic-co-glycolic acid NPs were therefore loaded with erythromycin (Er), an antibiotic with low membrane permeability that is susceptible to drug efflux, and 3c, a 5-cyanothiazolyl urea derivative with low solubility and stability. In vitro experiments demonstrated that the incorporation of small NPs into large Lip resulted in a reduction in NP uptake by HEK293 cells while increasing it in Gram-negative bacteria (Escherichia coli DH5α, E. coli K12, and Pseudomonas aeruginosa), consequently resulting in an enhancement of antibiotic selectivity by fourfold toward E. coli (both strains) and eightfold toward P. aeruginosa. Ocular administration of NP-Lip in a P. aeruginosa keratitis mouse model demonstrated the ability of Er/3c-loaded NP-Lip to result in a complete recovery. More importantly, in comparison to NPs, the ocular administration of NP-Lip showed a reduction in TNF-alpha and IL-6 levels, implying reduced interaction with mammalian cells in vivo. This work therefore clearly demonstrated how tailoring the nano-bio interaction could result in selective drug delivery and a reduction in toxicity.

The other side to the use of active targeting ligands; the case of folic acid in the targeting of breast cancer.

Due to its overexpression in cancer cells, the folate receptor (FR) is heavily exploited in the active targeting of nanoparticles (NPs). Its ligand, folic acid (FA) is as a consequence widely used as a NP targeting ligand. Although rather popular and successful in principle, recent data has shown that FA may result in breast cancer initiation and progression, which questions the suitability of FA as NP cancer targeting ligand. In this work, intravenous administration of free FA to healthy female mice resulted in breast tissue dysplasia, hyperplasia and in the increased expression of human epidermal growth factor receptor-2 (HER2), folate receptor (FR), cancer antigen 15-3 (CA15.3), vascular endothelial growth factor (VEGF), signal transducer and activator of transcription 3 (STAT3) and the pro-inflammatory cytokines, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6) and interleukin-1ß. In addition to the reduction in IL2. To evaluate the suitability and safety of FA as NP targeting ligand in breast cancer, small (≈ 150 nm) and large (≈ 500 nm) chitosan NPs were formulated and decorated with two densities of FA. The success of active targeting by FA was confirmed in two breast cancer cell lines (MCF-7 and MDA-MB-231 cells) in comparison to HEK293 cells. FA modified NPs that demonstrated successful active targeting in-vitro were assessed in-vivo. Upon intravenous administration, large NPs modified with a high density of FA accumulated in the breast tissue and resulted in similar effects as those observed with free FA. These results therefore question the suitability of FA as a targeting ligand in breast cancer and shed light on the importance of considering the activity (other than targeting) of the ligands used in NP active targeting.

Prevention of hepatic stellate cell activation using JQ1- and atorvastatin-loaded chitosan nanoparticles as a promising approach in therapy of liver fibrosis.

Preventing hepatic stellate cell (HSC) activation represents a promising approach to resolve liver fibrosis. Several drugs have been reported to delay/prevent HSCs activation, however with limited clinical benefits. The latter may be in part attributed to the limited ability of such drugs in targeting more than one pathway of HSC activation. Added to that, is their inability of reaching their target cell in sufficient amounts to induce a therapeutic effect. In this work, chitosan NPs were loaded with JQ1 and atorvastatin, two drugs that have been reported to prevent HSCs activation, however via different mechanisms. NPs were then modified with different densities of retinol (Rt) for active targeting of HSCs. The NP HSCs targeting ability as a function of Rt density was assessed in vitro on primary HSCs and in vivo in carbon tetrachloride (CCl4) induced fibrotic mouse models. In vitro NPs modified with a low Rt density (LRt-NPs) showed ≈2 folds enhanced HSCs uptake in comparison to unmodified NPs, whereas NPs modified with a high Rt density (HRt-NPs) showed ≈0.8 folds change in uptake relative to unmodified NPs. Similarly, in vivo LRt-NPs showed higher accumulation in fibrotic livers in comparison to healthy livers whereas HRt-NPs and unmodified NPs showed lower accumulation in fibrotic livers relative to healthy controls respectively. Finally, the ability of drug-loaded NPs in preventing HSCs activation was assessed by monitoring the reduction in α-smooth muscle actin (α-SMA) expression by Western blot. NPs loaded with both JQ1 and atorvastatin showed reduction in α-SMA expression. In addition, a synergistic reduction in α-SMA was observed when cells were co-treated with JQ1 and atorvastatin loaded NPs.