Superfast and controllable microfluidic inking of anti-inflammatory melanin-like nanoparticles inspired by cephalopods

Here, a microfluidic approach for superfast melanin-like nanoparticle preparation with tunable size and monodispersity is reported. The particles formed have similar chemical composition to those prepared by the bulk method, and show reactive oxygen species scavenging behaviour and inflammatory macrophage phenotype switching capability, suggesting their potential for anti-inflammatory applications.Peer reviewe

Evaluation of dendrimers as a potential oral drug delivery system

Dendrimers are novel nanoscale sized macromolecules that have a well-defined highly branched structure and a large number of reactive chain-ends. Here the potential use of dendrimers as an oral drug delivery system has been evaluated. First experiment designed to assess the in vitro biocompatibility of cationic branched polymers; poly(vinylamine)(vinylformamide) (PVF) copolymers and two different classes of dendrimers; diaminoethane (DAE) and polyamidoamine (PAMAM) dendrimers of different generation (Mw 289-50,865 Da) and different surface characteristics (-COONa, -NH2). The haemolysis of PVF copolymers is increased as a function of amine content. Dendrimers with an amine surface were generally toxic depending on their concentration and generation. In contrast, dendrimers with carboxylate surface were shown to be biocompatible. Non-toxic PAMAM dendrimers were radioiodinated and used to investigate their ability to traverse rat intestinal tissue in vitro. The rate of serosal transfer and tissue uptake for anionic dendrimers was in the range of 3.4-4.4 and 0.6-2.5 μl/mg protein/h, respectively, whereas for cationic dendrimers these values were in the range of 2.3-2.7 and 3.3-4.8 μl/mg protein/h. After oral administration in vivo, most of the dose recovered was found in stomach and small intestine in 1 h, and after 5 h entered the caecum and colon. By 24 h most radioactivity (70-90% of the recovered dose) was located in faeces. The amount of radioactivity found in the blood was insignificant (0.1- 1%). As 10-30% of the administered dose was not found in the organs studied the extent of oral absorption of dendrimer is so far inconclusive. Finally studies were carried out using PAMAM dendrimers to investigate their ability to complex with piroxicam and indomethacin. Dendrimer gen 3 formed complexes with both drugs in aqueous solution. However, the interaction showed insufficient control of drug release to allow in vivo application. Therefore, a preliminary study was conducted to synthesis and characterise covalent drug-dendrimer conjugates using ibuprofen as a model drug. Overall the observations made in these studies show that dendrimers do have potential as drug carriers for oral delivery and in future dendrimers must be more specifically designed to promote oral absorption and subsequent controlled release

รายงานการวิจัยฉบับสมบูรณ์เรื่องการพัฒนาการนำส่งยาต้านอักเสบ 5-อะมิโนซาลิซิลิก แอซิดสู่ลำไส้ใหญ่ส่วนโคลอนโดยการเชื่อมต่อกับโพลิเอทิลีนกลัยคอล

Prince of Songkla Universit

Alginate-Based Composite Sponges as Gastroretentive Carriers for Curcumin-Loaded Self-Microemulsifying Drug Delivery Systems

Alginate-based composite sponges were developed as carriers to prolong the gastric retention time and controlled release of curcumin-loaded self-microemulsifying drug delivery systems (Cur-SMEDDS). Liquid Cur-SMEDDS was incorporated into a solution made up of a mixture of polymers and converted into a solid form by freeze-drying. The ratio of alginate as the main polymer, adsorbent (colloidal silicon dioxide), and additional polymers—sodium carboxymethyl cellulose (SCMC), hydroxypropyl methylcellulose (HPMC)—was varied systematically to adjust the drug loading and entrapment efficiency, sponge buoyancy, and the release profile of Cur-SMEDDS. The optimum composite sponge was fabricated from a 4% alginate and 2% HPMC mixed solution. It immediately floated on simulated gastric fluid (SGF, pH 1.2) and remained buoyant over an 8 h period. The formulation exhibited an emulsion droplet size of approximately 30 nm and provided sustained release of Cur-SMEDDS in SGF, reaching 71% within 8 h compared with only 10% release from curcumin powder. This study demonstrates the potential of alginate-based composite sponges combined with self-microemulsifying formulations for gastroretention applications involving poorly soluble compounds

การสังเคราะห์และการออกฤทธิ์เป็น esterase และ amidase ของพอลิเมอร์-ทริปซิน คอนจุเกต

Prince of Songkla Universit

Influence of Natural Gum on Curcumin Supersaturationin Gastrointestinal Fluids

Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms.In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8)was investigated. The results indicated that all natural gums significantly increased the curcum insolubility (about 1.2-6-fold)when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF

Simultaneous Delivery of Curcumin and Resveratrol via In Situ Gelling, Raft-Forming, Gastroretentive Formulations

Curcumin and resveratrol are polyphenolic compounds that have been shown to exhibit synergistic therapeutic properties including anti-inflammatory, anticancer, and antiulcer activities, which may be exploited for the treatment of gastric diseases. However, both compounds have poor aqueous solubility and rapid metabolism, resulting in a low oral bioavailability. In situ gelling, liquid formulations were developed to produce a gastroretentive, raft-forming delivery vehicle to improve bioavailability. Solid dispersions containing a mixture of curcumin and resveratrol with Eudragit® EPO (Cur/Res-SD) were first prepared using solvent evaporation, to improve the solubility and dissolution of the compounds. Solid dispersions of a weight ratio of 1:10 curcumin/resveratrol to Eudragit® EPO were subsequently incorporated into in situ gelling, liquid formulations based on the gelling polymers, sodium alginate (low viscosity and medium viscosity), pectin, and gellan gum, respectively. Calcium carbonate and sodium bicarbonate were included to produce carbon dioxide bubbles in the gel matrix, on exposure to gastric fluid, and to achieve flotation. Moreover, the calcium ions acted as a crosslinking agent for the hydrogels. Optimized formulations floated rapidly (<60 s) in simulated gastric fluid (pH = 1.2) and remained buoyant, resulting in the gradual release of more than 80% of the curcumin and resveratrol content within 8 h. The optimized formulation based on medium-viscosity sodium alginate exhibited enhanced cytotoxic activity toward human gastric adenocarcinoma cell lines (AGS), compared with unformulated curcumin and resveratrol compounds, and increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate that in situ gelling, liquid formulations, loaded with a combination of curcumin and resveratrol in the form of solid dispersions, show potential as gastroretentive delivery systems for local and systemic effects