Razvoj i vrednovanje mikrospužvastih sustava etilceluloze i ksantan gume za kontroliranu perkutanu isporuku diklofenak natrija

In this study, xanthan gum-facilitated ethyl cellulose microsponges were prepared by the double emulsification technique and subsequently dispersed in a carbopol gel base for controlled delivery of diclofenac sodium to the skin. Scanning electron microscopy revealed the porous, spherical nature of the microsponges. Increase in the drug/polymer ratio (0.4:1, 0.6:1, 0.8:1, m/m) increased their yield (79.1–88.5 %), drug entrapment efficiency (50.0–64.1 %), and mean particle diameter (181–255 µm). Compared to the microsponges with high drug/polymer ratio (0.8:1, m/m), the flux of entrapped drug through excised rat skin decreased by 19.9 % and 17.0 %, respectively, for the microsponges prepared at low and intermediate drug/polymer ratios. When an equivalent amount of pure drug (not entrapped into microsponges) was dispersed into the gel base and the flux was compared, the microsponges (drug/polymer ratio 0.8:1, m/m) were found to reduce the flux by 33.3 %. Whether the drug was dispersed either in un-entrapped or entrapped form into the gel base, the drug permeation through rat skin followed Higuchi\u27s diffusion kinetic model. The microsponges prepared at the lowest drug/polymer ratio exhibited a comparatively slower drug permeation profile and were hence considered most suitable for controlled drug delivery application. FTIR spectroscopy and DSC analyses indicated the chemically stable, amorphous nature of the drug in these microsponges. The gel containing these optimized microsponges was comparable to that of a commercial gel formulation and did not show serious dermal reactions. Hence, the microsponge system obtained at the lowest drug/polymer ratio could be useful for controlled release of diclofenac sodium to the skin.U radu su opisani mikrospužvasti sustavi s etilcelulozom i ksantan gumom pripravljeni metodom dvostruke emulzifikacije i dispergirani u podlogu s karbopol gelom za kontrolirano oslobađanje diklofenak natrija na kožu. Elektronska pretražna mikroskopija potvrdila je poroznu, sferičnu strukturu mikrospužvastih sustava. Povećanjem omjera lijeka i polimera (0,4:1, 0,6:1, 0,8:1, m/m) povećalo se iskorištenje (79,1–88,5 %), količina uklopljenog lijeka (50,0–64,1 %) i srednji promjer čestica (181–255 µm). Prolaz uklopljenog lijeka kroz izrezane komade kože štakora smanjio se za 19,9 %, odnosno 17,0 %, kada se omjer lijeka i polimera smanjio s visokog (0,8:1, m/m) na niski i srednji. Oslobađanje iz mikrospužvastih struktura s omjerom lijeka i polimera 0,8:1 (m/m) smanjeno je za 33,3 % u odnosu na oslobađanje ekvivalentne količina lijeka koji nije uklopljen već samo dispergiran u geliranu podlogu. Ako je lijek bio dispergiran kao neuklopljen ili kao uklopljen u geliranu podlogu, permeacija lijeka kroz kožu štakora slijedila je Higuchijev difuzijski kinetički model. Mikrospužvaste strukture pripravljene uz najniži omjer lijeka i polimera pokazale su sporiji permeacijski profil pa ih smatramo najpovoljnijima za kontrolirano oslobađanje lijeka. FTIR spektroskopija i DSC analiza pokazale su da je lijek u mikrospružvastim sustavima stabilan i amorfan. Gel s optimiranim mikrospužvastim sustavom sličan je komercijalnom gelu i ne pokazuje ozbiljne kožne reakcije. Sustav pripravljen s najnižim omjerom lijeka i polimera mogao bi biti pogodan za kontrolirano oslobađanje diklofenak natrija na kožu

Carboxymethylation of Locust Bean Gum: Application in Interpenetrating Polymer Network Microspheres for Controlled Drug Delivery

For hydrophilic modification, the sodium carboxymethyl ether of locust bean gum was developed by Williamson synthesis using monochloroacetic acid as the etherifying agent. The modification reaction was optimized in terms of concentration of monochloroacetic acid and sodium hydroxide. The modified gum was evaluated for its degree of substitution, elemental analysis, viscosity, swelling, and contact angle. The etherification of locust bean gum was further confirmed by FTIR, ¹³C NMR, DSC, and XRD techniques. Acute oral toxicity and biodegradability studies showed that the modified gum was safe enough for internal use. This carboxymethylated gum with poly­(vinyl alcohol) was utilized to prepare the interpenetrating polymer network microspheres of buflomedil hydrochloride for controlled drug delivery. The microspheres were evaluated for their drug entrapment efficiency, swelling, and particle size. The microspheres were further characterized by FTIR, ¹³C NMR, and XRD techniques. The in vitro release study of microspheres showed retarded drug release up to 12 h

Synchronous semi-solid extrusion and photopolymerization of antimicrobial dressing hydrogel for wound healing

Bacterial infections at wound sites require more time for a fast and efficient wound-healing process. Antibacterial methyl cellulose-based hydrogel wound dressing can be an excellent option because it can show antibacterial action, absorb wound exudates, and have a cooling and soothing effect on the wound bed. The ultraviolet (UV) ray-assisted semi-solid extrusion 3D printing technique was used to prepare 3D printed construct into a high surface area mesh-like structure utilizing UV radiation for photocrosslinking of hydrogel matrix in the presence of Poly (ethylene glycol) Diacrylate. The prepared hydrogel was characterized for contact angle, and rheological analysis before semi-solid extrusion-based 3D printing. After optimization of printing parameters, the 3D printed mesh was subjected to physicochemical characterizations like dimensional analysis, swelling study, drug content, in vitro drug release, and in vitro antimicrobial activity study. A rheological analysis confirmed the viscosity, thixotropy, and viscoelastic nature of prepared hydrogel. Drug release study showed approximately 50 % release in 4 h, and >80 % drug release in 24 h. After optimization of one batch, hydrogel polymerization was done by functional group analysis followed by validation of thread thickness by electron microscopy images and mechanical property assessment. The 3D-printed mesh was further evaluated for its in-vitro antibacterial performance against Escherichia coli and Staphylococcus aureus. The area of inhibition was one-fold more in Staphylococcus aureus and two-fold in E. coli, ensuring diffusion of the drug from 3D printed mesh and killing of bacteria. The work reported herein represents a universal platform to generate multifunctional and customized hydrogels with various functional substances for wound dressing applications

Investigation on crosslinking density for development of novel interpenetrating polymer network (IPN) based formulation

777-784Interpenetrating polymer network (IPN) based formulation, consisting of sodium alginate and poly vinyl alcohol, were prepared by water-in-oil emulsion crosslinking method. IPN based formulation was cross-linked with glutaraldehyde, and loaded with diclofenac sodium (DS) as a model drug. Scanning electron microscopy revealed spherical nature of microspheres (size, 472-157 m). Drug entrapment efficiency (72%) was obtained depending upon concentration of crosslinking density. Novel formulation can be a potential carrier for controlled delivery of short half-lived drugs

Solubility Enhancement of Ezetimibe by a Cocrystal Engineering Technique

The present study illustrates the formation and characterization of three different cocrystals of ezetimibe using methyl paraben as a coformer, employing three different processes, namely, solution crystallization, liquid assisted grinding, and reaction crystallization. Thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis were used as a primary analytical tool, followed by spectroscopic and crystallographic study as a confirmatory analytical tool. Equilibrium aqueous solubility studies were performed for all cocrystals taking ezetimibe as the control. The ideal solubility of drug and cocrystals was also calculated using data obtained from DSC (heat of fusion, Δ<i>H</i>, and transition melting temperature, <i>T</i>_m). The equilibrium aqueous solubility of ezetimibe was enhanced by about 2-fold in the case of cocrystal prepared by solution crystallization. Cocrystals prepared via reaction crystallization showed solubility that was almost the same as that of pure ezetimibe. The dissolution profile of all cocrystals, with pure ezetimibe as a control, was studied for 2 h in defined biorelevant media. Cocrystal II, prepared by a liquid assisted grinding method, showed significant improvement in solubility at 45 and 120 min, indicating a good dissolution profile. The study demonstrates that pharmaceutical cocrystallization of ezetimibe with methyl paraben can be a possible and potential alternative and effective approach for improving its solubility

Exploring the interaction between extracellular matrix components in a 3D organoid disease model to replicate the pathophysiology of breast cancer

In vitro models are necessary to study the pathophysiology of the disease and the development of effective, tailored treatment methods owing to the complexity and heterogeneity of breast cancer and the large population affected by it. The cellular connections and tumor microenvironments observed in vivo are often not recapitulated in conventional two-dimensional (2D) cell cultures. Therefore, developing 3D in vitro models that mimic the complex architecture and physiological circumstances of breast tumors is crucial for advancing our understanding of the illness. A 3D scaffold-free in vitro disease model mimics breast cancer pathophysiology by allowing cells to self-assemble/pattern into 3D structures, in contrast with other 3D models that rely on artificial scaffolds. It is possible that this model, whether applied to breast tumors using patient-derived primary cells (fibroblasts, endothelial cells, and cancer cells), can accurately replicate the observed heterogeneity. The complicated interactions between different cell types are modelled by integrating critical components of the tumor microenvironment, such as the extracellular matrix, vascular endothelial cells, and tumor growth factors. Tissue interactions, immune cell infiltration, and the effects of the milieu on drug resistance can be studied using this scaffold-free 3D model. The scaffold-free 3D in vitro disease model for mimicking tumor pathophysiology in breast cancer is a useful tool for studying the molecular basis of the disease, identifying new therapeutic targets, and evaluating treatment modalities. It provides a more physiologically appropriate high-throughput platform for screening large compound library in a 96-384 well format. We critically discussed the rapid development of personalized treatment strategies and accelerated drug screening platforms to close the gap between traditional 2D cell culture and in vivo investigations. </p

Exploring the interaction between extracellular matrix components in a 3D organoid disease model to replicate the pathophysiology of breast cancer

In vitro models are necessary to study the pathophysiology of the disease and the development of effective, tailored treatment methods owing to the complexity and heterogeneity of breast cancer and the large population affected by it. The cellular connections and tumor microenvironments observed in vivo are often not recapitulated in conventional two-dimensional (2D) cell cultures. Therefore, developing 3D in vitro models that mimic the complex architecture and physiological circumstances of breast tumors is crucial for advancing our understanding of the illness. A 3D scaffold-free in vitro disease model mimics breast cancer pathophysiology by allowing cells to self-assemble/pattern into 3D structures, in contrast with other 3D models that rely on artificial scaffolds. It is possible that this model, whether applied to breast tumors using patient-derived primary cells (fibroblasts, endothelial cells, and cancer cells), can accurately replicate the observed heterogeneity. The complicated interactions between different cell types are modelled by integrating critical components of the tumor microenvironment, such as the extracellular matrix, vascular endothelial cells, and tumor growth factors. Tissue interactions, immune cell infiltration, and the effects of the milieu on drug resistance can be studied using this scaffold-free 3D model. The scaffold-free 3D in vitro disease model for mimicking tumor pathophysiology in breast cancer is a useful tool for studying the molecular basis of the disease, identifying new therapeutic targets, and evaluating treatment modalities. It provides a more physiologically appropriate high-throughput platform for screening large compound library in a 96-384 well format. We critically discussed the rapid development of personalized treatment strategies and accelerated drug screening platforms to close the gap between traditional 2D cell culture and in vivo investigations. </p

Surface engineered nanodiamonds: mechanistic intervention in biomedical applications for diagnosis and treatment of cancer

In terms of biomedical tools, nanodiamond (ND) is a more recent innovation. Their size ranged from 4 to 100 nm. ND is produced via a variety of methods and is known for its physical toughness, durability, and chemical stability. The study revealed that surface modifications and functionalization have a significant influence on the optical and electrical properties of the nanomaterial. ND's surface functional groups have applications in a variety of domains, including drug administration, gene delivery, immunotherapy for cancer treatment, and bio-imaging to diagnose cancer. The biocompatibility of a material is critical for in vivo and in vitro interventions. This review focuses on recent advances in the methods of ND synthesis and ND-assisted drug delivery, moving through studies in cellular and animal models and bio-imaging for other biomedical applications. Furthermore, the prognosis of its clinical translation is being studied. </p