Investigation of the Pristine and Functionalized Carbon Nanotubes as a Delivery System for the Anticancer Drug Dacarbazine: Drug Encapsulation

Carbon Nanotubes (CNTs) have been used as the systems in drug delivery due to their exceptional physical and chemical properties. In this study, the adsorption of an anticancer drug Dacarbazine (DAC) into the inner and outer surface of pristine and Functionalized Carbon Nanotubes (FCNTs) with four carboxylic acid groups was investigated in aqueous solution using the Molecular Dynamics (MD) simulations. Our simulation results showed that in spite of the adsorption of drug molecules on the outer sidewall of pristine and functionalized nanotubes, the spontaneous encapsulation of DAC molecule into the cavity of CNTs and FCNTs is observed. The simulations show that the arrangement of the DAC molecule into the CNTs and FCNTs is controlled by π-π interactions.     

Etiology and management of the hypertensive phase in glaucoma drainage-device surgery

Insertion of glaucoma drainage devices has become a mainstay in the surgical management of multiple forms of glaucoma, and the indications for this procedure continue to expand. A unique clinical challenge in the postoperative care of these devices is the hypertensive phase, a period of postoperative intraocular pressure elevation in the first three months after surgery. We discuss the influence of a variety of factors on the development of the hypertensive phase after glaucoma drainage implantation, including type of device, device material, and device surface area. Furthermore, several intraoperative and postoperative interventions are investigated as attempts to mitigate this phenomenon. Included among these are the use of antimetabolites, collagen matrix, and a variety of approaches to postoperative inflammation and intraocular pressure control. We provide an overview of our current knowledge of the etiology and management of the hypertensive phase.     

Improved survival of anchorage-dependent cells in core-shell hydrogel microcapsules via co-encapsulation with cell-friendly microspheres

In this study, we investigated the effect of intracapsular environment on the survival of anchorage-dependent cells (ADCs) encapsulated in alginate microcapsules with three different core structures, i.e. liquid, semi-liquid and microsphere-encapsulating semi-liquid core, using NIH 3T3 fibroblasts as an ADC model. For the latter, we fabricated poly (?-caprolactone) microspheres and co-encapsulated them with the cells, to establish cell-substrate interactions in the capsule. The fibroblast cells co-encapsulated with the microspheres exhibited higher survival and growth than those without. This study provides a “proof of concept” for employing microspheres as a cell-friendly surface to establish intracapsular cell-substrate interactions thus prolonging the survival of encapsulated therapeutic ADCs.     

Impact of the type of emulsifier on the physicochemical characteristics of the prepared fish oil-loaded microcapsules

Fish oil microcapsules were successfully prepared from fish oil-in-water emulsions using chitosan as shell material and anionic surfactants sodium dodecyl sulphate (SDS), sodium dodecylbenzenesulfonate (SDBS), sodium cholate (cholate), and sodium deoxycholate (DOC) as emulsifiers. The type of emulsifier influenced the physicochemical characteristics of the prepared microcapsules to different extents. The microcapsules formed with DOC showed the least mean effective diameter (MED) of 500?nm. Emulsion formed with DOC exhibited the smallest MED of 100?nm. The emulsions showed negative zeta potential values which became positive after encapsulation with chitosan. The surfactants showed little influence on thermal stability. Microcapsule suspensions showed creaming over storage. Fish oil at higher loading in SDS microcapsules showed higher primary and secondary oxidation. All microcapsules showed sustained release but the values varied depending upon the surfactants. The emulsion and microcapsules formed with DOC showed better morphology and stability despite its lower loading and encapsulation efficiency.     

Novel food drug interaction mechanism involving acyclovir,chitosan and endogenous mucus

Drug absorption from drug products may be affected by pharmaceutical excipients and/or food additives through different mechanisms. Chitosan is a recognized nutraceutical, with potential as an excipient due to its permeability enhancer properties. While chitosan properties have been evaluated in in vitro and pre-clinical models, studies in humans are scarce. Unexpectedly, a controlled clinical trial showed chitosan actually reduced acyclovir bioavailability. The effect seems to be related to an interaction with gastrointestinal mucus that prevents further absorption, although more in depth research is needed to unravel the mechanism. In this paper, we propose a mechanism underlying this excipient effect. The mucus – chitosan interaction was characterized and its effect on acyclovir diffusion, permeation and bioaccessibility was investigated. Further, pharmacokinetic modeling was used to assess the clinical relevance of our findings. Results suggest that in situ coacervation between endogenous mucus and chitosan rapidly entrap 20–30% of acyclovir dissolved dose in the intestinal lumen. This local reduction of acyclovir concentration together with its short absorption window in the small intestine would explain the reduction in acyclovir C_max and AUC. This study highlights the importance of considering mucus in any biorelevant absorption model attempting to anticipate the effect of chitosan on drug absorption.     

PAMAM‐Conjugated Alumina Nanotubes as Novel Noncytotoxic Nanocarriers with Enhanced Drug Loading and Releasing Performances

Alumina nanotubes are surface‐conjugated with polyamidoamine (PAMAM) dendrimers of the third generation, aimed at obtaining novel nanomaterials for drug delivery applications. The structure and surface properties of PAMAM‐conjugated alumina nanotubes (PAMAM‐Al₂O₃NT) are characterized using Fourier Transform Infrared spectroscopy, solid state ¹³C‐RMN, transmission electron microscopy, N₂ adsorption–desorption isotherms, X‐ray powder diffraction (XRD), and thermogravimetric analysis (TGA), which supported for a 3.0 wt% of PAMAM grafting in the prepared product. The drug loading and releasing properties of PAMAM‐Al₂O₃NT are examined using three model therapeutic compounds, namely, curcumin, methotrexate, and silibinin, showing that PAMAM conjugation enhances the drug loading capacity and drug‐adsorbent affinity compared to pristine Al₂O₃NT systems. Additionally, Alamar Blue cell viability assays reveal that PAMAM‐Al₂O₃NT are not cytotoxic materials over a wide concentration range. These results suggest that PAMAM–Al₂O₃NT are potential nanostructured vehicles for drug delivery applications.

     

Formulation and stability evaluation of 3D alginate beads potentially useful for cumulus–oocyte complexes culture

Ovarian follicle encapsulation in synthetic or natural matrixes based on biopolymers is potentially a promising approach to in vitro maturation (IVM) process, since it maintains follicle 3D organisation by preventing its flattening and consequent disruption of gap junctions, preserving the functional relationship between oocyte and companion follicle cells. The aim of the work was to optimise physico-chemical parameters of alginate microcapsules for perspective IVM under 3D environments. On this purpose alginate and cross-linking agent concentrations were investigated. Alginate concentration between 0.75% and 0.125% w/w and Mg²⁺, Ba²⁺, Ca^2+?at concentration between 100 and 20?mM were tested. Follicle encapsulation was obtained by on purpose modified diffusion setting gelation technique, and evaluated together with beads, chemical and mechanical stability in standard and stressing conditions. Beads permeability was tested towards albumin, fetuin, pyruvate, glucose, pullulan. Results demonstrated that 0.25% alginate cross-linked in 100?mM CaCl₂ beads is suitable to follicle encapsulation.     

芦丁微囊的制备及其质量评价

目的:研究芦丁微囊的制备工艺,并对其进行质量评价。方法:以明胶为囊材,采用单凝聚法制备芦丁微囊,通过正交设计优化其制备工艺,并对包封率、载药量、微囊的粒径分布、体外释放进行研究。结果:用本方法制备芦丁微囊的最佳工艺是明胶质量浓度为3%,囊心囊材比为1︰2,成囊温度为60℃,搅拌速度为400 r·min-1。此工艺所制得芦丁微囊的平均包封率为75.24%,有76.40%的微囊粒径分布在20～35μm,平均载药量为32.04%,体外释放在0.5 h达到30.48%,12 h累积释放达到90%以上。结论:以最佳工艺条件制备的含药微囊,重复性好,工艺稳定,同时体外释放试验表明,该微囊具有较好的缓释作用。     

Tuning the dependency between stiffness and permeability of a cell encapsulating hydrogel with hydrophilic pendant chains

The mechanical stiffness of a hydrogel plays a significant role in regulating the phenotype of cells that adhere to its surface. However, the effect of hydrogel stiffness on cells cultured within its matrix is not well understood, because of the intrinsic inverse dependency between the permeability and stiffness of hydrogels. This study therefore presents an advanced biomaterial design strategy to decrease the inverse dependency between permeability and stiffness of a cell encapsulating hydrogel. Hydrogels were made by cross-linking poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) monoacrylate (PEGMA), with PEGMA acting as a pendant polymer chain. Increasing the mass fraction of PEGMA while keeping the total polymer concentration constant led to a decrease in the elastic modulus (E) of the hydrogel, but caused a minimal increase in the swelling ratio (Q). The size and hydrophobicity of the end groups of pendant PEG chains further fine tuned the dependency between Q and E of the hydrogel. Pure PEGDA hydrogels with varying molecular weights, which show the same range of E but a much greater range of Q, were used as a control. Fibroblasts encapsulated in PEGDA–PEGMA hydrogels displayed more significant biphasic dependencies of cell viability and vascular endothelial growth factor (VEGF) expression on E than those encapsulated in pure PEGDA hydrogels, which were greatly influenced by Q. Overall, the hydrogel design strategy presented in this study will be highly useful to better regulate the phenotype and ultimately improve the therapeutic efficacy of a wide array of cells used in various biology studies and clinical settings.