The rapid development of nanotechnology offers a variety of potential therapeutic strategies for cancer treatment. High atomic element nanomaterials are often utilized as radiosensitizers due to their unique photoelectric decay characteristics. Among them, gold nanoparticles (GNPs) are one of the most widely investigated and are considered to be an ideal radiosensitizers for radiotherapy due to their high X-ray absorption and unique physicochemical properties. Over the last few decades, multidisciplinary studies have focused on the design and optimization of GNPs to achieve greater dosing capability and higher therapeutic effects and highlight potential mechanisms for radiosensitization of GNPs. Although the radiosensitizing potential of GNPs has been widely recognized, its clinical translation still faces many challenges. This review analyses the different roles of GNPs as radiosensitizers in cancer radiotherapy and summarizes recent advances. In addition, the underlying mechanisms of GNP radiosensitization, including physical, chemical and biological mechanisms are discussed, which may provide new directions for the optimization and clinical transformation of next-generation GNPs.

The purpose of this study is to determine whether sodium alginate solutions' rheological parameters are meaningful relative to sodium alginate's use in the formulation of calcium alginate gels. Calcium alginate gels were prepared from six different grades of sodium alginate (FMC Biopolymer), one of which was available in ten batches. Cylindrical gel samples were prepared from each of the gels and subjected to compression to fracture on an Instron Universal Testing Machine, equipped with a 1-kN load cell, at a cross-head speed of 120 mm/min. Among the grades with similar % G, (grades 1, 3, and 4), there is a significant correlation between deformation work (L(E)) and apparent viscosity (η(app)). However, the results for the partial correlation analysis for all six grades of sodium alginate show that L(E) is significantly correlated with % G, but not with the rheological properties of the sodium alginate solutions. Studies of the ten batches of one grade of sodium alginate show that η(app) of their solutions did not correlate with L(E) while tan δ was significantly, but minimally, correlated to L(E). These results suggest that other factors--polydispersity and the randomness of guluronic acid sequencing--are likely to influence the mechanical properties of the resultant gels. In summary, the rheological properties of solutions for different grades of sodium alginate are not indicative of the resultant gel properties. Inter-batch differences in the rheological behavior for one specific grade of sodium alginate were insufficient to predict the corresponding calcium alginate gel's mechanical properties.

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In this work, a biodegradable poly(ethylene glycol)-poly(epsilon-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) triblock copolymer was successfully synthesized. The aqueous solution of such PECE copolymer displayed special sol-gel-sol transition as temperature increase, which is a flowing sol at low-temperature and turns into a nonflowing gel at body temperature. The cytotoxicity of PECE copolymer was evaluated by cell viability assay using HEK 293 cells. In vivo gel formation and degradation test based on intraperitoneal and subcutaneous administration was conducted, respectively. The acute toxicity test and histopathological study were performed in BALB/c mice by intrapleural, intraperitoneal, or subcutaneous administration of PECE hydrogel (30 Wt %), respectively. The dose of intrapleural, intraperitoneal, or subcutaneous administration was up to 10 g/kg body weight (b.w.), 25 g/kg b.w., and 25 g/kg b.w., respectively, and the mice were observed continuously for 14 days. For histopathologic study, samples including heart, liver, lung, kidneys, spleen, stomach, intestine, and tissue of injection site were prepared for histochemical analysis and were stained with hematoxylin-eosin. No mortality or significant signs of acute toxicity was observed during the whole observation period and there is no significant lesion to be shown in histopathologic study of major organs. Therefore, the maximum tolerance dose of PECE hydrogel by intrapleural, intraperitoneal, or subcutaneous administration was calculated to be higher than 10 g/kg b.w., 25 g/kg b.w., and 25 g/kg b.w., respectively. The results indicated that the prepared PECE hydrogel was nontoxic after intrapleural, intraperitoneal, or subcutaneous administration, and it could be a safe candidate for in situ gel-forming controlled drug delivery system.

Background The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) is predominantly hampered by low accumulation in tumor tissue and the high systemic toxicity of anticancer drugs. In this study, we designed an in situ drug-loaded injectable thermosensitive hydrogel system for the simultaneous delivery of norcantharidin-loaded nanoparticles (NCTD-NPs) and doxorubicin (Dox) via intratumoral administration to HCC tumors. Methods NCTD-NPs were prepared by the thin film dispersion method using PCEC polymers as the carrier. Then, NCTD-NPs and Dox were co-encapsulated in a thermosensitive hydrogel based on Pluronic F127 (PF127) to construct a dual drug-loaded hydrogel system. The rheological properties of the drug-loaded hydrogel were studied using a rheometer. Drug release of the drug-loaded hydrogel and cytotoxicity in HepG2 cells were evaluated in vitro. An H22 tumor-bearing mice model was used to assess the in vivo antitumor activity of the drug-loaded hydrogel via intratumoral administration. Results The prepared drug-loaded hydrogel exhibited good thermal-sensitive properties, which remained liquid at room temperature and rapidly transformed into a non-flowing gel at body temperature, and released the drugs in a sustained manner. In vitro studies revealed that the drug-loaded hydrogel exhibited remarkable antiproliferative activity in HepG2 cells compared to free drugs. In vivo antitumor efficacy experiments showed that the drug-loaded hydrogel significantly suppressed tumor growth, alleviated side effects, and prolonged the survival time of mice bearing H22 tumors compared to the other groups. Moreover, immunohistochemical staining revealed that the expression of Ki-67 and CD31 in the drug-loaded hydrogel group was significantly lower than that in the other groups (P < 0.05), indicating that the drug-loaded hydrogel effectively inhibited tumor proliferation and angiogenesis. Conclusion The formulated hybrid thermosensitive hydrogel system with sustained drug release and enhanced therapeutic efficacy was demonstrated to be a promising strategy for the local-regional treatment of HCC via intratumoral administration.

Colorectal peritoneal carcinomatosis (CRPC) is a common systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy against CRPC is at present the preferred treatment. The aim of this study is to develop a novel hydrogel drug delivery system through the combination of 5-fluorouracil (5-FU) loaded polymeric micelles and cisplatin (DDP) in biodegradable thermosensitive chitosan (CS) hydrogel. The prepared CS hydrogel drug is a free-flowing solution at room temperature and forms a stationary gel at body temperature. Therefore, a CRPC mouse model is established to investigate the antitumor activity of CS hydrogel drug system. The results suggest that intraperitoneal administration of CS hydrogel drug can inhibit tumor growth and metastasis, and prolong survival time compared with other groups, thus improving the chemotherapeutic effect. Ki-67 immunohistochemical analysis reveals that tumors in the CS hydrogel drug group has lower cell proliferation in contrast to other groups (P < 0.001). Furthermore, hematoxylin-eosin staining of liver and lung tissue indicates that the CS hydrogel drug has also a certain inhibitory effect on colorectal cancer metastasis to the liver and lung. Hence, the work highlights the potential clinical applications of the CS hydrogel drug.

Abstract. Polymeric excipients are often the least well-characterized components of pharmaceutical formulations. The aim of this study was to facilitate the QbD approach to pharmaceutical manufacturing by evaluating the inter-grade and inter-batch variability of pharmaceutical-grade polymeric excipients. Sodium alginate, a widely used polymeric excipient, was selected for evaluation using appropriate rheological methods and test conditions. The materials used were six different grades of sodium alginate and an additional ten batches of one of the grades. To compare the six grades, steady shear measurements were conducted on solutions at 1%, 2%, and 3% w/w, consistent with their use as thickening agents. Small-amplitude oscillation (SAO) measurements were conducted on sodium alginate solutions at higher concentrations (4-12% w/w) corresponding to their use in controlled-release matrices. In order to compare the ten batches of one grade, steady shear and SAO measurements were performed on their solutions at 2% w/w and 8% w/w, respectively. Results show that the potential interchangeability of these different grades used as thickening agents could be established by comparing the apparent viscosities of their solutions as a function of both alginate concentration and shear conditions. For sodium alginate used in controlled-release formulations, both steady shear behavior of solutions at low concentrations and viscoelastic properties at higher concentrations should be considered. Furthermore, among batches of the same grade, significant differences in rheological properties were observed, especially at higher solution concentrations. In conclusion, inter-grade and inter-batch variability of sodium alginate can be determined using steady shear and small-amplitude oscillation methods.

Nano-hydroxyapatite (n-HA)/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) composite membranes were prepared by solvent casting and evaporation method. The structure and properties of the membranes were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), water contact angle measurements, in vitro hydrolytic degradation, mechanical test, and cell culture. The effect of n-HA content on physical-chemical properties of the n-HA/PCEC composite membranes was studied. The results showed that the shape and size of micropores of the composite membranes changed with n-HA content increased; the tensile strength decreased with the increase of n-HA content. The osteoblast cell was cultured on the membranes, good cell attachment and growth manner were observed after postseeding for 1 day. MTT assays showed that the n-HA/PCEC membranes had no negative effect on the cell viability and proliferation. These results suggested that the obtained n-HA/PCEC composite membranes in this study might have prospective applications in tissue engineering field.