Systematic Investigation of Biocompatible Cationic Polymeric Nucleic Acid Carriers for Immunotherapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third-largest cause of cancer death worldwide, while immunotherapy is rapidly being developed to fight HCC with great potential. Nucleic acid drugs are the most important modulators in HCC immunotherapy. To boost the efficacy of therapeutics and amplify the efficiency of genetic materials, biocompatible polymers are commonly used. However, under the strong need of a summary for current developments of biocompatible polymeric nucleic acid carriers for immunotherapy of HCC, there is rare review article specific to this topic to our best knowledge. In this article, we will discuss the current progress of immunotherapy for HCC, biocompatible cationic polymers (BCPs) as nucleic acid carriers used (or potential) to fight HCC, the roles of biocompatible polymeric carriers for nucleic acid delivery, and nucleic acid delivery by biocompatible polymers for immunotherapy. At the end, we will conclude the review and discuss future perspectives. This article discusses biocompatible polymeric nucleic acid carriers for immunotherapy of HCC from multidiscipline perspectives and provides a new insight in this domain. We believe this review will be interesting to polymer chemists, pharmacists, clinic doctors, and PhD students in related disciplines.

Effect of a novel thiazole derivative and its complex with polymeric carriers on the activity of antioxidant enzymes in murine lymphoma cells

Background. Previous studies have shown a pronounced cytotoxic effect of thiazole derivatives in combination with polymeric carriers on tumor cells. At the same time, the derivatives were not cytotoxic against non-cancerous cells in vitro. It was shown that thiazole derivatives at concentrations of 10 and 50 μM affected the prooxidant and antioxidant systems of lymphoma cells in vitro. The aim of this work was to study the effect of the complex of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) in combination with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th1), poly(PEGMA) (Th3) and poly(PEGMA-co-DMM) (Th5) on the antioxidant defense system of the NK/Ly cell in vitro. Materials and Methods. The experiments were performed on white wild-type male mice with grafted NK/Ly lymphoma. Tumor cells were inoculated into mice intraperitoneally. Ascites was drained from the abdominal cavity of anaesthetized mice with a sterile syringe on the 7th-10th day after inoculation. Investigated compounds BF1, BF1 + Th1 (Th2, Th12), BF1 + Th3 (Th4, Th14), BF1 + Th5 (Th6, Th16) at a final concentration of 10 μM were added to the lymphoma samples and incubated for 10 min; the activity of antioxidant enzymes was determined according to the techniques described previously. Results. It was found that all the studied complexes based on thiazole derivative BF1 and polymeric carriers poly (VEP-co-GMA)-graft-mPEG (Th2, Th12), poly (PEGMA) (Th4, Th14) and poly (PEGMA-co-DMM) (Th6, Th16) at a concentration of 10 μm increased the activity of SOD, while the activity of CAT and GPX were reduced compared to control. Complexes Th2, Th12 and Th4 increased the significance of the BF1 influence on lymphoma cells from P <0.05 to P <0.01. Pure polymeric carriers did not affect the level of the antioxidant defense system enzymes. Conclusions. Thus, it was found that the polymeric carriers in combination with thiazole derivative BF1 increased the significance of thiazole derivative BF1 influence on the activity of the antioxidant defense system of lymphoma cells, while pure polymeric carriers did not affect the activity of SOD, CAT or GPX. The results of this work can be used for further studies of complexes of thiazole derivative and PEG-containing polymeric carriers as potential antitumor drugs.

The Influence of the Hydrophobic Polymeric Coating on 5-ASA Release from the Bipolymeric Milibeads with Amidated Pectin

The industrial polymeric carriers for peroral mesalazine application exploit, i.a., cellulose or polyacrylic acid derivatives, polyvinylpyrrolidone, and modified starch. Pectins, as natural polymers, are interesting materials in pharmaceutical applications due to properties such as non-toxicity, biocompatibility, and biodegradability. The aim of the study was the evaluation of the release of the drug from coated pectin beads doped with synthetic polymers as drug carriers to the colon, as well as interactions between ingredients. The drug release was carried out using basket apparatus. The amount of 5-ASA (5-aminosalicylic acid, mesalazine) released to the pH = 7.4 buffer with pectinase was measured at selected time intervals using UV-Vis spectroscopy. The zero-, first-, and second-order kinetics, as well as Higuchi, Korsmeyer–Peppas, and Hixon–Crowell equations, were used to analyze the release pattern. The interactions between beads components were investigated employing FTIR spectrophotometry and DSC study. The dissolution of the drug was divided into two parts. It was found that the release of 5-ASA followed mainly the Higuchi equation. The mass transport in the first stage of the release followed a non-Fickian model and the parameter n was in the range of 0.74 ± 0.2–0.99 ± 0.2. The formulation doped with PA (polyacrylic acid) was the most appropriate and capable of overcoming the variable conditions of the gastrointestinal tract.

Polymeric Nanoparticles Decorated with Monoclonal Antibodies: A New Immobilization Strategy for Increasing Lipase Activity

Recent advances in nanotechnology techniques enable the production of polymeric nanoparticles with specific morphologies and dimensions and, by tailoring their surfaces, one can manipulate their characteristics to suit specific applications. In this work we report an innovative approach for the immobilization of a commercial lipase from Candida rugosa (CRL) which employs nanostructured polymeric carriers conjugated with anti-lipase monoclonal antibodies (MoAbs). MoAbs were chemically conjugated on the surface of polymeric nanoparticles and used to selectively adsorb CRL molecules. Hydrolytic enzymatic assays evidenced that such immobilization technique afforded a significant enhancement of enzymatic activity in comparison to the free enzyme.

Introduction of Re(CO)3+/99mTc(CO)3+ Organometallic Species into Vinylpyrrolidone-Allyliminodiacetate Copolymers

N-vinylpyrrolidone-co-allylamine copolymers (VP-co-AA) containing iminodiacetic (IDA) chelation units were prepared in the range of molecular masses of the copolymers from 9000 to 30,000 Da depending on polymerization conditions. Non-radioactive organometallic species Re(CO)3+ were introduced into polymeric carriers under mild conditions; the prepared metal–polymeric complexes were characterized by IR, NMR, ESI-MS and HPLC. IR spectra data confirmed the coordination of M(CO)3+ moiety to the polymeric backbone via IDA chelation unit (appearance of characteristic fac-M(CO)3+ vibrations (2005, 1890 cm−1), as well as the appearance of group of signals in 1H NMR spectra, corresponding to those inequivalent to methylene protons CH2COO (dd, 4.2 ppm), coordinated to metal ions. The optimal conditions for labeling the PVP-co-AA-IDA copolymers with radioactive 99mTc(CO)3+ species were determined. The radiochemical yields reached 97%. The obtained radiolabeled polymers were stable in blood serum for 3 h. In vivo distribution experiments in intact animals showed the high primary accumulation of technetium-99m MPC (MM = 15,000 Da) in blood with subsequent excretion via the urinary tract.

Polymeric Carriers Designed for Encapsulation of Essential Oils with Biological Activity

The article reviews the possibilities of encapsulating essential oils EOs, due to their multiple benefits, controlled release, and in order to protect them from environmental conditions. Thus, we present the natural polymers and the synthetic macromolecular chains that are commonly used as networks for embedding EOs, owing to their biodegradability and biocompatibility, interdependent encapsulation methods, and potential applicability of bioactive blend structures. The possibilities of using artificial intelligence to evaluate the bioactivity of EOs—in direct correlation with their chemical constitutions and structures, in order to avoid complex laboratory analyses, to save money and time, and to enhance the final consistency of the products—are also presented.