BAPTA-AM Nanoparticle for the Curing of Acute Kidney Injury Induced by Ischemia/Reperfusion.

Ischemia-reperfusion (I/R) is a major cause of acute kidney injury (AKI), which is associated with unacceptably high mortality rates in ICU. This research was designed to explore the therapeutic effect of BAPTA-AM (1,2-Bis(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester)) nanoparticle (BA-N) on AKI. BA-N was developed by liposome strategy and characterized by standard methods. The rat model was selected and the rats were randomly allocated into four groups: (1) Normal group; (2) Sham-operated group; (3) Model group (I/R + NS); (4) BA-N treatment group (I/R + BA-N). AKI model was established via clipping the bilateral renal artery with a microvascular clamp for 45 min. After reperfusion, serum cystatin C (Cys C), creatinine (Cr), blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and caspase 3 levels were determined for the assessment of renal function. Kidney samples were then collected for the measurement of renal malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. The assays of histological examination, ELISA, immunohistochemistry, western blot, TUNEL and RT-PCR were utilized for the detection of apoptosis. The results demonstrated that AKI model caused a significant decreasing in SOD activity, accompanied by a remarkable increase in Cys C, Cr, BUN, LDH, MDA, caspase 3 and cytochrome c (Cyt C) level, compared to the control group. BA-N (100 µg/kg i.v.) significantly improved renal function and histopathological appearance, restored MDA level and SOD activity, decreased Bax/Bcl-2 ratio, caspase 3 activity, Cyt C release and TUNEL positive apoptotic cells. Our studies indicated that BA-N plays a renal-protective role, probably through antiapoptotic and antioxidant mechanisms. BA-N may regulate mitochondria pathway via decreasing Bax/Bcl-2 ratio, inhibiting caspase 3 expression and Cyt C release. Overall, BA-N may have potentials as an anti-AKI drug.

Effect of taste masking technology on fast dissolving oral film: dissolution rate and bioavailability.

Fast dissolving oral film is a stamp-style, drug-loaded polymer film with rapid disintegration and dissolution. This new kind of drug delivery system requires effective taste masking technology. Suspension intermediate and liposome intermediate were prepared, respectively, for the formulation of two kinds of fast dissolving oral films with the aim of studying the effect of taste masking technology on the bioavailability of oral films. Loratadine was selected as the model drug. The surface pH of the films was close to neutral, avoiding oral mucosal irritation or side effects. The thickness of a 2 cm × 2 cm suspension oral film containing 10 mg of loratadine was 100 µm. Electron microscope analysis showed that liposomes were spherical before and after re-dissolution, and drugs with obvious bitterness could be masked by the encapsulation of liposomes. Dissolution of the two films was superior to that of the commercial tablets. Rat pharmacokinetic experiments showed that the oral bioavailability of the suspension film was significantly higher than that of the commercial tablets, and the relative bioavailability of the suspension film was 175%. Liposomal film produced a certain amount of improvement in bioavailability, but lower than that of the suspension film.

Self-assembly of peptide amphiphiles for drug delivery: the role of peptide primary and secondary structures.

Peptide amphiphiles (PAs), functionalized with alkyl chains, are capable of self-assembling into various nanostructures. Recently, PAs have been considered as ideal drug carriers due to their good biocompatibility, specific biological functions, and hypotoxicity to normal cells and tissues. Meanwhile, the nanocarriers formed by PAs are able to achieve controlled drug release and enhanced cell uptake in response to the stimulus of the physiological environment or specific biological factors in the location of the lesion. However, the underlying detailed drug delivery mechanism, especially from the aspect of primary and secondary structures of PAs, has not been systematically summarized or discussed. Focusing on the relationship between the primary and secondary structures of PAs and stimuli-responsive drug delivery applications, this review highlights the recent advances, challenges, and opportunities of PA-based functional drug nanocarriers, and their potential pharmaceutical applications are discussed.

Development of graphene oxide-wrapped gold nanorods as robust nanoplatform for ultrafast near-infrared SERS bioimaging.

The rapid development of near-infrared surface-enhanced Raman scattering (NIR SERS) imaging technology has attracted strong interest from scientists and clinicians due to its narrow spectral bandwidth, low background interference, and deep imaging depth. In this report, the graphene oxide (GO)-wrapped gold nanorods (GO@GNRs) were developed as a smart and robust nanoplatform for ultrafast NIR SERS bioimaging. The fabricated GO@ GNRs could efficiently load various NIR probes, and the in vitro evaluation indicated that the nanoplatform could exhibit a higher NIR SERS activity in comparison with traditional gold nanostructures. The GOs were prepared by directly pyrolyzing citric acid for greater convenience, and GO@GNRs were fabricated via a facile synthesis strategy. Higher NIR SERS activity, facile synthesis method, excellent biocompatibility, and superb stability make the GO@GNRs/probe complex promising nanoprobes for NIR SERS-based bioimaging applications.

pH-sensitive peptide hydrogel for glucose-responsive insulin delivery.

Glucose-responsive system is one of important options for self-regulated insulin delivery to treat diabetes, which has become an issue of great public health concern in the world. In this study, we developed a novel and biocompatible glucose-responsive insulin delivery system using a pH-sensitive peptide hydrogel as a carrier loaded with glucose oxidase, catalase and insulin. The peptide could self-assemble into hydrogel under physiological conditions. When hypoglycemia is encountered, neighboring alkaline amino acid side chains are significantly repulsed due to reduced local pH by the enzymatic conversion of glucose into gluconic acid. This is followed by unfolding of individual hairpins, disassembly and release of insulin. The glucose-responsive hydrogel system was characterized on the basis of structure, conformation, rheology, morphology, acid-sensitivity and the amount of consistent release of insulin in vitro and vivo. The results illustrated that our system can not only regulate the blood glucose levels in vitro but also in mice models having STZ-induced diabetes. STATEMENT OF SIGNIFICANCE: In this report, we have shown the following significance supported by the experimental results. 1. We successfully developed, characterized and screened a novel pH-responsive peptide. 2. We successfully developed a novel and biocompatible pH-sensitive peptide hydrogel as glucose-responsive insulin delivery system loaded with glucose oxidase, catalase and insulin. 3. We successfully confirmed that the hydrogel platform could regulate the blood glucose level in vitro and in vivo. Overall, we have shown enough significance and novelty with this smart hydrogel platform in terms of biomaterials, peptide chemistry, self-assembly, hydrogel and drug delivery. So we believe this manuscript is suitable for Acta Biomaterialia.

Development of collagen/polydopamine complexed matrix as mechanically enhanced and highly biocompatible semi-natural tissue engineering scaffold.

To improve the mechanical properties and biocompatibility of collagen I matrix, a novel and facile strategy was developed to modify porcine acellular dermal matrix (PADM) via dopamine self-polymerization followed by collagen immobilization to enhance the biological, mechanical and physicochemical properties of PADM. Mechanism study indicated that the polymerization of dopamine onto PADM surface could be regulated by controlling the amount of hydrogen bonds forming between phenol hydroxyl (COH) and nitrogen atom (NCO) within collagen fibers of PADM. The investigations of surface interactions between PDA and PADM illustrated that PDA-PADM system yielded better mechanical properties, thermal stability, surface hydrophilicity and the structural integrity of PADM was maintained after dopamine coating. Furthermore, collagen (COL) was immobilized onto the fresh PDA-PADM to fabricate the collagen-PDA-PADM (COL-PDA-PADM) complexed scaffold. The MTT assay and CLSM observation showed that COL-PDA-PADM had better biocompatibility and higher cellular attachment than pure PADM and COL-PADM without dopamine coating, thus demonstrating the efficacy of PDA as the intermediate layer. Meanwhile, the expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) of COL-PDA-PADM were investigated by an in vivo study. The results revealed that COL-PDA-PADM could effectively promote bFGF and VEGF expression, possibly leading to enhancing the dura repairing process. Overall, this work contributed a new insight into the development of a semi-natural tissue engineering scaffold with high biocompatibility and good mechanical properties. STATEMENT OF SIGNIFICANCE: Obtaining scaffolds with high biocompatibility and good mechanical properties is still one of the most challenging issues in tissue engineering. To have excellent in vitro and in vivo performance, scaffolds are desired to have similar mechanical and biological properties as the natural extracellular matrix, such as collagen based matrix. Utilizing the surface self-crosslinking and coating strategy, we successfully obtained a novel semi-natural platform with excellent biological and mechanical properties from porcine acellular dermal matrix (PADM), polydopamine and collagen. The results confirmed that this scaffold platform has very excellent cellular performance and very little toxicity/side effects in vivo. Therefore, this semi-natural scaffold may be an appropriate platform for tissue engineering and this strategy would further help to develop more robust scaffolds.

Polymer-based nanoparticles for protein delivery: design, strategies and applications.

Therapeutic proteins have attracted significant attention as they perform vital roles in various biological processes. The delivery of therapeutic proteins to target sites is, however, challenging due to their intrinsic sensitivity to different environmental conditions. Polymeric nanoparticles (NPs) can offer not only physical protection from environmental stimuli but also targeted delivery of such proteins to specific sites. In particular, NPs containing charged polymers are preferred for many applications as they provide gentle protection through electrostatic interactions. Moreover, most organs exhibit a specific pH, and by tuning the extent of the electrostatic interactions and contact duration between the target organ and polymeric NPs, the intracellular uptake of the latter and thus long-term therapeutic efficacy can be optimized. In this article, we will critically discuss the design considerations of charged polymeric NPs, strategies for and routes of protein delivery and how these are influenced depending on the choice of delivery route.