Chitosan Based MicroRNA Nanocarriers

International audienceVectorization of microRNAs has shown to be a smart approach for their potential delivery to treat many diseases (i.e., cancer, osteopathy, vascular, and infectious diseases). However, there are barriers to genetic in vivo delivery regarding stability, targeting, specificity, and internalization. Polymeric nanoparticles can be very promising candidates to overcome these challenges. One of the most suitable polymers for this purpose is chitosan. Chitosan (CS), a biodegradable biocompatible natural polysaccharide, has always been of interest for drug and gene delivery. Being cationic, chitosan can easily form particles with anionic polymers to encapsulate microRNA or even complex readily forming polyplexes. However, fine tuning of chitosan characteristics is necessary for a successful formulation. In this review, we cover all chitosan miRNA formulations investigated in the last 10 years, to the best of our knowledge, so that we can distinguish their differences in terms of materials, formulation processes, and intended applications. The factors that make some optimized systems superior to their predecessors are also discussed to reach the highest potential of chitosan microRNA nanocarriers

Hydralazine HCl rapidly disintegrating sublingual tablets: simple dosage form of higher bioavailability and enhanced clinical efficacy for potential rapid control on hypertensive preeclampsia

Samar Genedy,1 Ahmed Khames,2,3 Amal Hussein,4 Hatem Sarhan4 1Department of Clinical Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics and Pharmacy Technology, College of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt Background: Hypertensive disorders are the most common complication in pregnancy which can even lead to maternal mortality. Hydralazine hydrochloride (HHC), a direct-acting vasodilator, is intravenously used as the first-line therapy in controlling hypertension in pregnancy (preeclampsia). It suffers poor oral bioavailability (26%–50%) due to first-pass metabolism.Objective: This work aims for the preparation of HHC rapidly disintegrating sublingual tablets of higher absorption rate, short onset of action, and higher bioavailability for rapid control on blood pressure (BP) in hypertensive emergencies especially preeclampsia.Methods: HHC sublingual tablet mixtures were prepared using starch sodium glycolate and Pharmaburst as super disintegrants at three different levels by direct compression and were subjected to full in vitro evaluation; the drug bioavailability from the optimized sublingual tablet formula was assessed in comparison to conventional oral tablets in rabbits, and the clinical efficacy on controlling BP in induced preeclampsia like mouse model was also studied.Results: The results indicated compatibility of the prepared tablet mixtures, good flow, and acceptable mechanical strength. Sublingual tablet formula containing Pharmaburst (7%) that showed fastest disintegration (21 seconds) and 100% drug release within 5 minutes was selected for further bioavailability and pharmacodynamic studies. The drug bioavailability was significantly increased with Cmax = 28.2767±4.61 µg/mL, AUC(0–α) = 52.85±3.18 µg.h/mL, and Tmax = 0.33±0.011 hour in comparison to 18.0633±23.2 µg/mL, 33.18±5.18 µg.h/mL, and 0.75±0.025 hour for conventional oral tablets. Results of pharmacodynamic studies proved significant rapid control on both systolic and diastolic BP to normal values within only 30 minutes without any significant difference from intravenous data.Conclusion: These results confirm the suitability of the prepared HHC sublingual tablets for use in rapid control on hypertensive crisis especially in pregnant women as an alternate to parenteral administration.Keywords: pre-eclampsia like mouse model, absorption from buccal cavity, preeclampsia, sublingual tablets, hypertension, L-NAM

Green nanotechnology—An innovative pathway towards biocompatible and medically relevant gold nanoparticles

International audienceIn this review, we focus on recent advances in green nanotechnology, providing details on reliable synthetic pathways towards biocompatible and medically relevant gold and radioactive gold nanoparticles. We cover a wide plethora of synthetic protocols that utilize green nanotechnology with in-depth understanding of what makes a green process green. In section 2, we provide full details on the intervention of green nanotechnology for the production of various functionalized gold nanoparticles (AuNPs). Section 3 focuses on various characterization tools to be used for the complete physicochemical, size and in vitro characterization of gold nanoparticles before translating them into potential in vivo applications. Section 4 focuses on the science and applications of gold nanoparticles in diagnostic imaging. Specifically, we have highlighted the importance of the chemistry and physics of gold nanoparticles for applications in a myriad of diagnostic imaging including X-ray contrast agents, in single photon emission computed tomography (SPECT) imaging, positron-emission tomography (PET) imaging, optical coherence tomography (OCT), fluorescence imaging, magnetic resonance imaging (MRI), in surface enhanced Raman spectroscopy (SERS), and in ultrasound (US) imaging. Section 5 discusses latest advances on gold nanoparticles in drug delivery, gold nanoparticles in photothermal therapy and radioactive gold nanoparticles in cancer therapy. In particular, we discuss green nanotechnological interventions on how the electron rich phytochemicals including epigallocatechin gallate (EGCG) from tea, mangiferin (MGF) from mango and allied phytochemicals can be utilized in their dual roles, as reducing agents as well as rendering tumor specificity due to their strong tumor cell receptor avidity-to produce tumor specific molecular imaging and therapy agents. We also discuss latest advances on the importance of gold nanoparticles in X-ray Therapy. Important aspects relating to systemic toxicity of gold nanoparticles and ways to mitigate toxicity issues for their effective implementation in biomedical sciences are also discussed in section 6. The topics covered are intended to answer questions including why we should use green processes and what is the role of nanomedicine in the domain of human health and hygiene. Most importantly, we provide critical analysis on the ubiquitous role of gold nanoparticles in nanomedicine

Creating 3D objects with integrated electronics via multiphoton fabrication in vitro and in vivo

3D objects with integrated electronics were produced using an additive manufacturing approach relying on multiphoton fabrication (direct laser writing, DLW). Conducting polymer-based structures (with micrometer-millimeter scale features) were printed within exemplar matrices, including an elastomer (polydimethylsiloxane, PDMS) widely investigated for biomedical applications. The fidelity of the printing process in PDMS was assessed by optical coherence tomography, and the conducting polymer structures were demonstrated to be capable of stimulating mouse brain tissue in vitro. Furthermore, the applicability of the approach to printing structures in vivo was demonstrated in live nematodes (Caenorhabditis elegans). These results highlight the potential for such additive manufacturing approaches to produce next-generation advanced material technologies, notably integrated electronics for technical and medical applications (e.g., human-computer interfaces)

Effect of dietary supplementation of betaine and organic minerals on growth performance, serum biochemical parameters, nutrients digestibility, and growth-related genes in broilers under heat stress

Global warming and climate changes have a detrimental impact on poultry production, causing substantial economic losses. This study investigated the effects of incorporating dietary betaine (BT) and organic minerals (OMs) on broilers’ performance as well as their potential to mitigate the negative impacts of heat stress (HS). Six hundred 1-day-old Ross 308 chicks were randomly allocated to 12 experimental treatments with 5 replicates of 10 birds each (5 male + 5 female). The birds were provided with diets containing BT (0 and 2,000 ppm) and OMs (0, 250, and 500 ppm), either individually or in combination, under both thermoneutral and HS-inducing temperatures. The HS conditions involved exposing the birds to cyclic periods of elevated temperature (35°C ± 2°C) for 6 h daily, from 10:00 am to 4:00 pm, starting from d 10 and continuing until d 35. The exposure to HS deteriorated birds’ growth performance; however, dietary BT and OMs inclusion improved the growth performance parameters bringing them close to normal levels. Carcass traits were not affected by dietary supplementation of BT, OMs, HS, or their interaction. Interestingly, while HS led to increased (P < 0.05) levels of total cholesterol, LDL-cholesterol, and hepatic malondialdehyde (MDA), these adverse effects were mitigated (P < 0.05) by the addition of BT and OMs. Moreover, dietary BT supplementation led to elevated serum total protein and globulin concentrations. Cyclic HS did not alter Mn, Zn, and Cu contents in the pectoral muscle. However, the incorporation of OMs at both levels increased concentrations of these minerals. Notably, the combination of 500 ppm OMs and 2,000 ppm BT improved Mn, Zn, Cu, and Fe digestibility, which has been compromised under HS conditions. Cyclic HS upregulated gene expression of interleukin-1β, heat shock protein 70, and Toll-like receptor-4 while downregulated the expression of claudin-1, uncoupling protein, growth hormone receptor, superoxide dismutase 1, glutathione peroxidase 1 and insulin-like growth factor 1. The aforementioned gene expressions were reversed by the combination of higher dietary levels of BT and OMs. In conclusion, the dietary supplementation of 500 ppm OMs along with 2,000 ppm BT yielded significant improvements in growth performance and mineral digestibility among broiler chickens, regardless of thermal conditions. Moreover, this combination effectively restored the expression of growth-related genes even under heat-stress conditions

Creating 3D Objects with Integrated Electronics via Multiphoton Fabrication In Vitro and In Vivo

3D objects with integrated electronics are produced using an additive manufacturing approach relying on multiphoton fabrication (direct laser writing, (DLW)). Conducting polymer-based structures (with micrometer-millimeter scale features) are printed within exemplar matrices, including an elastomer (polydimethylsiloxane, (PDMS)) have been widely investigated for biomedical applications. The fidelity of the printing process in PDMS is assessed by optical coherence tomography, and the conducting polymer structures are demonstrated to be capable of stimulating mouse brain tissue in vitro. Furthermore, the applicability of the approach to printing structures in vivo is demonstrated in live nematodes (Caenorhabditis elegans). These results highlight the potential for such additive manufacturing approaches to produce next-generation advanced material technologies, notably integrated electronics for technical and medical applications (e.g., human-computer interfaces)