Vincentjonasson4842

Intratumoral injections of CpG showed the slowest tumor growth but exhibited dramatically higher systemic proinflammatory cytokine levels compared to polyplexes of GA with CpG. Sequencing of RNA from resected tumors revealed a similar pattern of upregulated proinflammatory cytokines for CpG and polyplexes, a finding supported by histological tumor staining showing similar infiltration of immune cells induced by these treatments. Intratumoral administration of polyplexes of GA with immunostimulant represents a translational approach to enhance local immune responses while mitigating systemic immune-related adverse events.New liposomes modified with pyrrolidinium surfactants containing a hydroxyethyl fragment (CnPB, n = 12, 14, 16) were prepared for transdermal delivery of non-steroidal anti-inflammatory drugs. In order to obtain the optimal composition, the surfactant/lipid molar ratio (0.02/1; 0.029/1; 0.04/1) and the amphiphile hydrocarbon tail length were varied. Rhodamine B was loaded in all formulations, while meloxicam and ketoprofen in selected ones. For liposomes studied the hydrodynamic diameter was in the range of 80-130 nm, the zeta potential ranged from +35 to +50 mV, EE was 75-99%. Liposome modification leads to a prolonged release of the rhodamine B (up to 10-12 h) and faster release of non-steroidal drugs (up to 7-8 h) in vitro. The ability to cross the skin barrier using Franz cells was investigated for liposomal meloxicam and ketoprofen. The total amount of meloxicam and ketoprofen passed through the Strat-M® membranes during 51 h was 51-114 μg/cm2 and 87-105 μg/cm2 respectively. The evaluation of transdermal diffusion ex vivo showed that total amount of liposomal ketoprofen passed through the skin during 51 h was 140-162 μg/cm2. Liposomes modified with C16PB were found as the most effective inflammation reducing formulation in the carrageenan edema model of rat paw.Nanomedicines have achieved several successful clinical applications for cancer therapy over the past decades. To date, numerous nanomedicine formats and design rationales have been proposed to improve pharmaceutical delivery and treatment efficacy. Despite these advances, the achievement of high drug loading and loading efficiencies of drug payloads in nanocarriers remains a technical challenge. In addition, study of the correlation between therapeutic potential and drug loading has been ignored. Here, using a self-assembling dimeric cabazitaxel prodrug, we show that the prodrug can be quantitatively entrapped within clinically approved polymer matrices for intravenous injection and that the drug loading in the nanoparticles (NPs) is tunable. The engineered NPs (NPs1-4) with different drug loading values exhibit dissimilar morphologies, release kinetics, in vitro cytotoxic activity, pharmacokinetic properties, tissue distribution, and in vivo anticancer efficacy and safety profiles. Furthermore, the effect of drug loading on the treatment outcomes was explored through detailed in vitro and in vivo studies. Cyclopamine price Intriguingly, among the constructed NPs, those comprising poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PLA) copolymers showed substantially prolonged pharmacokinetic properties in the blood circulation, which further promoted their intratumoral delivery and accumulation. Furthermore, the PEG-PLA-composed NPs with high drug loading (~50%) demonstrated favorable efficacy and safety profile in animal models. These data provide convincing evidence that the in vivo performance of a given self-assembling drug is not compromised by high drug loading in nanoplatforms, which may potentially reduce concerns over excipient-associated side effects and immunotoxicities. Overall, our study provides new insight into the rationale for designing more effective and less toxic delivery systems.Nanomedicines based on poly(lactic-co-glycolic acid) (PLGA) carriers offer tremendous opportunities for biomedical research. Although several PLGA-based systems have already been approved by both the Food and Drug Administration (FDA) and the European Medicine Agency (EMA), and are widely used in the clinics for the treatment or diagnosis of diseases, no PLGA nanomedicine formulation is currently available on the global market. One of the most impeding barriers is the development of a manufacturing technique that allows for the transfer of nanomedicine production from the laboratory to an industrial scale with proper characterization and quality control methods. This review provides a comprehensive overview of the technologies currently available for the manufacturing and analysis of polymeric nanomedicines based on PLGA nanoparticles, the scale-up challenges that hinder their industrial applicability, and the issues associated with their successful translation into clinical practice.Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72 × 10-6 cm2/s to 4.50 × 10-6 cm2/s. The gelation kinetics then is described with a "zero order" mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel.Co-amorphization has been utilized to improve the physical stability of the respective neat amorphous drugs. However, physical stability of co-amorphous systems is mostly investigated under dry conditions, leaving the potential influence of moisture on storage stability unclear. In this study, carvedilol-L-aspartic acid (CAR-ASP) co-amorphous systems at CAR to ASP molar ratios from 31 to 13 were investigated under non-dry conditions at two temperatures, i.e., 25 °C 55 %RH and 40 °C 55 %RH. Under these conditions, the highest physical stability of CAR-ASP systems was observed at the 11 M ratio. This finding differed from the optimal molar ratio previously obtained under dry conditions (CAR-ASP 11.5). Molecular interactions between CAR and ASP were affected by moisture, and salt disproportionation occurred during storage. Morphological differences of systems at different molar ratios could be observed already after one week of storage. Furthermore, variable temperature X-ray powder diffraction measurements showed that excess CAR or excess ASP, existing in the binary systems, resulted in a faster recrystallization compared to equimolar system.