Current Drug Delivery - Volume 19, Issue 9, 2022

Nanomaterials can be applied in different biomedical applications like diagnosis, treatment, and drug delivery due to their unique features. Using such materials in the endodontic treatment processes may prove challenging as these materials must exhibit antibacterial effects without posing any harm to the host cells. The approach involving nanofibers loaded with various antibacterial drugs offers a potential treatment method to enhance the elimination procedure of intracanal biofilms. Clinically, many models of bacterial biofilms were prepared under in vitro conditions for different aims. The process of drug delivery from polymeric nanofibers is based on the principle that the releasing ratio of drug molecules increases due to the increase in the surface area of the hosted structure. Our review discusses diverse approaches to loading/releasing drugs on/from nanofibers; we summarized many studies on electrospun nanofibers loaded with various drugs applied in the endodontic field. Moreover, we discussed both the advantages and the limitations of these modern endodontic treatment materials, comparing them with the traditional ones.

Objective: This study aimed to prepare combretastatin A4 (CA4)-loaded nanoparticles (CA4 NPs) using poly(lactic-co-glycolic acid) (PLGA) and soybean lecithin (Lipoid S100) as carriers, and further evaluate the physicochemical properties and cytotoxicities of CA4 NPs against cancer cells. Methods: CA4 NPs were prepared using a solvent evaporation technique. The effects of formulations on CA4 NPs were investigated in terms of particle size, zeta potential, encapsulation efficacy, and drug loading. The physicochemical properties of CA4 NPs were characterized using transmission electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectra. The drug release from CA4NPs was performed using a dialysis method. In addition, the cytotoxicity of CA4NPs against human alveolar basal epithelial (A549) cells was also evaluated. Results: CA4 NPs prepared with a low organic/water phase ratio (1:20) and high drug/PLGA mass ratio (1:2.5) exhibited a uniform hydrodynamic particle size of 142 nm, the zeta potential of -1.66 mV, and encapsulation efficacy and drug loading of 92.1% and 28.3%, respectively. CA4 NPs showed a significantly higher release rate than pure CA4 in pH 7.4 phosphate-buffered solution with 0.5% Tween 80. It was found that the drug molecules could change from the crystal state to an amorphous form when loaded into the PLGA/Lipoid S100 matrix, and some molecular interactions could also occur between the drug and PLGA. Importantly, CA4 NPs showed a remarkably higher antiproliferation activity against A549 cancer cells compared to pure CA4. Conclusion: These results suggested the promising potential of PLGA/Lipoid S100 nanoparticles as the drug delivery system of CA4 for effective cancer therapy.

Background: Iron is used to alter macrophage phenotypes and induce tumor cell death. Iron oxide nanoparticles can induce macrophage polarization into the M1 phenotype, which inhibits tumor growth and can dissociate into iron ions in macrophages. Objective: In this study, we proposed to construct high expression of Ferroportin1 macrophages as carriers to deliver Fe3O4-nanoparticles and iron directly to tumor sites. Methods: Three sizes of Fe3O4-nanoparticles with gradient concentrations were used. The migration ability of iron-carrying macrophages was confirmed by an in vitro migration experiment and monocyte chemoattractant protein-1 detection. The release of iron from macrophages was confirmed by determining their levels in the cell culture supernatant, and we constructed a high expression of ferroportin strain of macrophage lines to increase intracellular iron efflux by increasing membrane transferrin expression. Fe3O4-NPs in Ana-1 cells were degraded in lysosomes, and the amount of iron released was correlated with the expression of ferroportin1. Results: After Fe3O4-nanoparticles uptake by macrophages, not only polarized macrophages into M1 phenotype, but the nanoparticles also dissolved in the lysosome and iron were released out of the cell. FPN1 is the only known Fe transporter; we use a Lentiviral vector carrying the FPN1 gene transfected into macrophages, has successfully constructed Ana-1-FPN1 cells, and maintains high expression of FPN1. Ana-1-FPN1 cells increase intracellular iron release. Fe3O4-nanoparticles loaded with engineered Ana-1 macrophages can act as a “reservoir” of iron. Conclusion: Our study provides proof of strategy for Fe3O4-NPs target delivery to the tumor microenvironment. Moreover, increase of intracellular iron efflux by overexpression of FPN1, cell carriers can act as a reservoir for iron, providing the basis for targeted delivery of Fe3O4-NPs and iron ions in vivo.

Introduction: Liposomes have been widely used in drug delivery systems because the encapsulation of liposomes changes the biological distribution profile and improves the therapeutic indices of various drugs. Thermosensitive liposomes have been proven to be a precise and effective method for cancer therapy in many preclinical studies. However, the lack of specific targeting ability to cancer cells limited their application in safe and efficient chemotherapy. Methods: In the present study, an ovarian targeting ligand namely WSGFPGVWGASVK (WSG) screened by phage display in vivo was grafted on the thermosensitive phospholipids to prepare the liposomes targeting ovarian cancer cells. WSG was first grafted onto the hydrophilic terminal of DSPEPEG2000 molecules, and then the WSG modified thermosensitive liposomes (WSG-Lipo) were prepared by thin-film hydration method. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate the drug release behavior of liposomes at different temperatures. The specificity of liposomes to SKOV-3 cells was studied by cell uptake in vitro. Results: The WSG-Lipo-DOX could release more DOX at 42°C than at 37°C, showing stronger specificity to SKOV-3 cells and thus selectively inhibiting SKOV-3 cells activity in vitro. Conclusion: The active targeting liposome showed potential in improving the specificity of thermosensitive liposomes and would be applied in the chemotherapy combined with a thermotherapy.

Background: Gastroretentive drug delivery systems (GRDDSs) are designed to release the drug in the stomach over a prolonged time; thus, they can reduce drug dosing frequency and dose size and improve patient compliance. GRDDSs are also highly effective in enhancing the bioavailability of the drug that exhibits window absorption in specific segments of the gastrointestinal (GI) tract. Famotidine (FMT), an H2 receptor antagonist, is an example of these drugs. FMT is a slightly watersoluble drug but well soluble in an acidic medium. This research aims to formulate FMT gastroretentive floating tablets (FMT-GRFTs) to improve the bioavailability and therapeutic activity of the drug and increase patients' adherence to treatment. In addition, the in vitro release behavior of the prepared FMT-GRFTs was quantitatively analyzed using the DDSolver software to assist in selecting the successful formulation that was then evaluated in vivo. Methods: The direct compression technique prepared numerous tablet formulations and was subjected to the pre-and post-compression evaluation. Data of FMT dissolution in the simulated gastric medium was analyzed by various kinetic models built in the DDSolver program. In addition, the simulated pharmacokinetics (AUC, MDT, and MRT), R2 adjusted, AIC, MSC, correlation of the residuals, and similarity factor (f2) were also generated. Results: The results revealed that FMT release from the candidate formula (FH3) fitted to the first-order kinetic model, with a high value of R2 adjusted and MSC and a low AIC. The release behavior exhibited the Fickian diffusion mechanism. The similarity factor showed no significant difference (p < 0.05) of the test sample compared to the reference product. Nevertheless, the simulated pharmacokinetic parameter, AUC, proved a two-fold enhancement in FMT bioavailability, with a significant increment in the MDT and MRT compared with the reference product. The FT-IR spectroscopy analysis indicated the absence of drug-excipients/polymer interaction. The in vivo X-ray studies on rabbits confirmed that the floating tablets showed nearly eight hours of gastric residence. Conclusion: DDSolver software was helpful in deciding the optimized formulation of FMT floating tablets. The radiological examination in rabbits for gastric retention was consistent with the release data analysis in vitro.

Introduction: Multi-drug nanosystem has been employed in several therapeutic models due to the synergistic effect of the drugs and/or bioactive compounds, which help in tumor targeting and limit the usual side effects of chemotherapy. Methods: In this research, we developed the amphiphilic Heparin-poloxamer P403 (HSP) nanogel that could load curcumin (CUR) and Paclitaxel (PTX) through the hydrophobic core of Poloxamer P403. The features of HSP nanogel were assessed through Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), differential light scattering (DLS), and critical micelle concentration (CMC). Nanogel and its dual drug-loaded platform showed high stability and spherical morphology. Results: The drug release profile indicated fast release at pH 5.5, suggesting effective drug distribution at the tumor site. In vitro research confirms lower cytotoxicity of HSP@ CUR@PTX compared to free PTX and higher inhibition effect with MCF-7 than HSP@PTX. These results support the synergism between PTX and CUR. Conclusion: HSP@CUR@PTX suggests a prominent strategy for achieving the synergistic effect of PTX and CUR to circumvent undesirable effects in breast cancer treatment.

Background: The plant used in the present study is Cassia fistula, which belongs to the family Leguminosae and has been used in traditional medicinal systems due to the presence of a copious amount of Phytochemicals with various properties. Aims: This study is focused on the extraction of phytochemicals from the Cassia fistula flower and its subsequent encapsulation into chitosan matrix for applications in drug delivery. Chitosan is approved by FDA for its use in Pharmaceutical industries. Methods: As described by several analytical techniques such as FT-IR, NMR, Thermal analysis, and SEM, the microsphere thus prepared by the current study is predicted to release the desired extract with medicinal properties in a controlled manner, allowing for more convenient and desired levels of drug administration. The swelling study and release study of the prepared microsphere have been carried out in physiological pH 2 and 7.4. NMR study has shown that sitosterol and friedelin have been encapsulated successfully into the chitosan matrix. Results: The microspheres have shown up to 80% swelling in pH 2 upto 8 days, and 60% of the in- -vitro controlled drug release has also been found in pH 2 upto 2 days. The thermal studies using TGA and DSC supported the thermal stabilities of CS beads, CFFE and CFFE-CS beads, Also, it showed the dispersion of the CFFE in the cavities of the Chitosan matrix. Conclusion: The Biomedical application of the synthesized CFFE-CS beads has also been reported on the basis of their antibacterial studies.