Endothelialisation and cell retention on gelation-chitosan coated electrospun polyurethane, poly (lactide-co-glycolide) and collagen-coated pericardium

Arterial bypass and heart valve replacements are two of the most common surgical treatments in cardiovascular surgery today. Currently, artificial materials are used as substitute for these cardiac tissues. However, these foreign materials do not have the ability to grow, repair or remodel and are thrombogenic, leading to stenosis. With the aid of tissue engineering, it is possible to develop functional identical copies of healthy heart valves and arteries, which are biocompatible. Although much effort has been made into this area, there are still inconsistencies with respect to
endothelialisation and cell retention on synthetic biological grafts. These variations may be attributed to differences in factors such as cell seeding density, incubation periods and effects of shear stress. In this study, we have compared the endothelialisation and cell retention between gelain chitosan-coated electrospun polyurethane (PU), poly (lactide co-glycolide) (PGA/PLA) and collagen-coated pericardium. Endothelial cells adhered to all of the materials as early as 1–day post seeding. After 7-day of seeding, the coverage on PU was almost 45% and that on PGA/PLA was about 25% and the least was on collagen-coated pericardium of approximately 15%. It was observed that the PU showed superior cell coverage and cell retention in comparison to the PGA/PLA and collagen-coated pericardium.

The miscibility of poly(d,l-lactide-co-glycolide) with amphiphilic molecules and the interaction of their mixtures with DNA at air/water interface

The miscibility of poly(d,l-lactide-co-glycolide) (PLG) with three amphiphilic molecules and the interaction of the PLG/surfactant mixtures with DNA at air/water interface are investigated by π-A isotherms, Brewster angle microscopy (BAM) and atomic force microscopy (AFM) techniques. The π-A isotherms of the PLG mixtures with cationic C12AzoC6PyBr, and C12AzoC6N(CH3)3Br, are quite different from the π-A isotherm of pure PLG on water subphase. In contrast to the case, the π-A isotherm of PLG mixed with nonionic C12AzoC6OPy is almost identical to the pure PLG except some increasing of molecular area. Similar phenomena are observed on DNA subphase. The in situ BAM and ex situ AFM observations demonstrate that the dispersion of PLG at air/water interface becomes good when it mixes with the two cationic surfactants, whereas quite poor due to the phase separation when it mixes with the nonionic amphiphilic molecule. Based on these results we conclude that the cationic surfactants can affect the conformation change of PLG at air/water interface and figure a well miscibility with polymer whereas the nonionic amphiphilic molecule presents poor miscibility. In addition, the even mixing of the PLG and the cationic surfactants is favorable for the adsorption to DNA more effectively.

Monolayer behavior of a pyridyl head-group-containing amphiphile and its miscibility with poly(D,L-lactide-co-glycolide) on different pH subphase

In this paper, we investigated the Langmuir film and Langmuir–Blodgett (LB) monolayer film of a nonionic amphiphilic molecule, 4-(6-p-pyridyloxyl)hexyloxyl-4′-dodecyloxylazobenzene (C12AzoC6Py) and its mixture with poly(d,l-lactide-co-glycolide) (PLG) at different subphase pH values (2.0, 2.6, 3.3, 4.4, and 6.5, respectively) by surface pressure–area (π–A) isotherms, in situ interface Brewster angle microscopy (BAM), and ex situ atomic force microscopy (AFM). For pure C12AzoC6Py, its π–A isotherms display a plateau when the subphase pH value is lower than 3.0. The pressure of the plateau increases with the decrease of pH until 2.0. Over the plateau, the π–A isotherms become almost identical to the one under neutral conditions. The appearance of such a plateau can be explained as the coexistence of protonation and unprotonation of pyridyl head groups of the employed amphiphile. In contrast to the homogeneous surface morphology of pure C12AzoC6Py near the plateau by BAM observation, the surface in the case of its mixing with PLG exhibits a dendritic crystalline state under low surface pressure at subphase pH lower than 3.0. The crystalline state becomes soft and gradually melts into homogeneous aggregates with surface pressure increasing to a higher value than that of the plateau. Meanwhile, the hydrolysis of PLG in the mixture system at the interface has been affirmed to be restrained to a very large extent. And the PLG was believed to be compelled to the up layer of the LB film due to the phase separation, which is examined by AFM. Based on the experimental results, the corresponding discussion was also performed.

Formulation optimization for high drug loading colonic drug delivery carrier

High drug loading (DL) carrier is an effective way to cure the cancerous cells. High drug loading is also one of the key issues in the drug delivery research, especially the colonic drug delivery system by oral administration. The times of drug intake could be remarkably reduced if high drug loading carriers are administered. At the same time, the related formulation materials could be effectively utilized. One major obstacle with the preparation of this system is the difficulty to encapsulate the hydrophilic drug into hydrophobic encapsulation polymer. A design of high drug loading delivery system with biodegradable, biocompatible materials and optimization of the fabrication process is a potential solution to solve the problem. So in this research, 5-Fluorouracil (5-FU) loaded Poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared by double emulsion and solvent evaporation method. Several fabrication parameters including theoretical drug loading, volume ratio of outer water phase to the first emulsion, pH value of outer aqueous phase and emulsifier PVA concentration were optimized to get a high drug loading nanoparticles. The result shows that with the increase of theoretical drug loading, the actual drug loading increased gradually. When adjusted the pH value of outer aqueous phase to the isoelectric point (8.02) of 5-Fluorouracil, the drug loading exhibited a higher one compared to other pH value solution. Relative higher volume ratio of outer water phase to the first emulsion was also beneficial for the enhancement of drug loading. But the nanoparticles size increased simultaneously due to the lower shearing force. When increased the PVA concentration, the drug loading showed an increase first and following a drop.

Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery

Shortage of functional groups on surface of poly(lactide-co-glycolide) (PLGA)-based drug delivery carriers always hampers its wide applications such as passive targeting and conjugation with targeting molecules. In this research, PLGA nanoparticles were modified with chitosan through physical adsorption and chemical binding methods. The surface charges were regulated by altering pH value in chitosan solutions. After the introduction of chitosan, zeta potential of the PLGA nanoparticle surface changed from negative charge to positive one, making the drug carriers more affinity to cancer cells. Functional groups were compared between PLGA nanoparticles and chitosan-modified PLGA nanoparticles. Amine groups were exhibited on PLGA nanoparticle surface after the chitosan modification as confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The modified nanoparticles showed an initial burst release followed by a moderate and sustained release profile. Higher percentage of drugs from cumulative release can be achieved in the same prolonged time range. Therefore, PLGA nanoparticles modified by chitosan showed versatility of surface and a possible improvement in the efficacy of current PLGA-based drug delivery system.

Multifunctional nanoparticle-EpCAM aptamer bioconjugates: a paradigm for targeted drug delivery and imaging in cancer therapy

The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific target site is crucial for providing efficient delivery of therapeutics and imaging agents. In this regard, the present study investigates the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles, functionalized with a targeting ligand (EpCAM aptamer) and an imaging agent (quantum dots) for cancer therapy and bioimaging. A wide spectrum of in vitro analysis (cellular uptake study, cytotoxicity assay, cell cycle and apoptosis analysis, apoptosis associated proteins study) revealed superior therapeutic potentiality of targeted drug loaded NPs over other formulations in EpCAM expressing cells. Moreover, our nanotheranostic system served as a superlative bio-imaging modality both in 2D monolayer culture and tumor spheroid model. Our result suggests that, these aptamer-guided multifunctional NPs may act as indispensable nanotheranostic approach toward cancer therapy.

Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer

The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide) (PLGA) and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA) and European Medicine Agency (EMA), making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs) have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined.

Nanoparticulate drug delivery to colorectal cancer : formulation strategies and surface engineering

The evolution of polymer-based nanoparticle as a drug delivery carrier has greatly contributed to the development of advanced nano and micro-medicine in the past few decades. The polymer-based nanoparticles of biodegradable and biocompatible polymers such as poly (lactide-co-glycolide) and chitosan which have been approved by Food & Drug Administration and/or European Medicine Agency can particularly facilitate the maintaining of specific properties for a real transition from laboratory to the clinical oral and parental administration. This review presents an overview of the strategies of preparing polymeric nanoparticles and using them for targeting colorectal cancer. Theranostics and surface engineering aspects of nanoparticle design in colonic cancer delivery are also highlighted.