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In recent years, to treat a diverse array of cancer forms, considerable advancements have been achieved in the field of cancer immunotherapies. However, these therapies encounter multiple challenges in clinical practice, such as high immune-mediated toxicity, insufficient accumulation in cancer tissues, and undesired off-target reactions. To tackle these limitations and enhance bioavailability, polymer micelles present potential solutions by enabling precise drug delivery to the target site, thus amplifying the effectiveness of immunotherapy. This review article offers an extensive survey of recent progress in cancer immunotherapy strategies utilizing micelles. These strategies include responsive and remodeling approaches to the tumor microenvironment (TME), modulation of immunosuppressive cells within the TME, enhancement of immune checkpoint inhibitors, utilization of cancer vaccine platforms, modulation of antigen presentation, manipulation of engineered T cells, and targeting other components of the TME. Subsequently, we delve into the present state and constraints linked to the clinical utilization of polymeric micelles. Collectively, polymer micelles demonstrate excellent prospects in tumor immunotherapy by effectively addressing the challenges associated with conventional cancer immunotherapies. [ABSTRACT FROM AUTHOR]

Abstract: The objectives of this study were to investigate the potential interactions between the model protein drug (bee venom peptide, BVP) and thermosensitive poly(dl-lactide-co-glycolide-b-ethyleneglycol-b-dl-lactide-co-glycolide) (PLGA–PEG–PLGA) copolymers and to examine the drug–copolymer interactions on the in vitro drug release and hydrogel degradation. The PLGA–PEG–PLGA copolymers were synthesized by ring-opening copolymerization of dl-lactide and glycolide with PEG as an initiator. Drug–copolymer co-precipitate blends were prepared and analyzed by Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) to characterize the specific interactions between drug and copolymer. For the better understanding the drug–copolymer interactions on drug release, insulin was selected for comparison. The release of the two protein drugs from the copolymer-based hydrogels and hydrogel degradation was studied at 37°C under agitation. The results of FTIR and XRD indicated that the hydrogen bonding interactions existed between the Nf BVP and Cf the copolymers. The insulin and BVP released from the copolymer hydrogel over 15 and 40 days, respectively. The BVP–copolymer interactions retarded the BVP release rate and degradation of hydrogel, but did not significantly affect the biological activity of BVP. These results indicate that the drug–copolymer interactions need to be considered when attempting to use PLGA–PEG–PLGA hydrogels as sustained delivery carriers of protein or peptide drugs. [Copyright &y& Elsevier]

Knee osteoarthritis (OA) is a common degenerative disease. Intra-articular administration of flurbiprofen is frequently employed in clinic to treat OA, while repeated injections are required because of the limited effective duration. To improve therapeutic outcome and prolong the treatment interval, a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA–PEG–PCLA) triblock copolymer based flurbiprofen thermosensitive gel for the sustained intra-articular drug delivery was designed in this study. The anti-OA effects of this flurbiprofen thermogel were investigated on collagenase II-induced rat knee OA model by multiple approaches and compared with that of conventional sodium hyaluronate and flurbiprofen injecta. In vitro drug release studies indicated that flurbiprofen was sustained released from the thermosensitive gel for more than three weeks. This sustained drug release system exerted comparable short-term analgesic effects and distinctly improved long-term analgesic efficacy in terms of the increased percentage of the total ipsilateral paw print intensity and the reduced Knee-Bend scores of OA rats. The inflammatory response was attenuated in the samples of flurbiprofen gel treated group by showing decreased IL-1, IL-6, and IL-11 levels in the joint fluid and down-regulated IL-1, IL-6, IL-11, COX-2, TNF-α, and NF-κB/p65 expression in the articular cartilages. The results suggest the suitability of thermosensitive copolymer PCLA–PEG–PCLA for sustained intra-articular effects of flurbiprofen and provide in vivo experimental evidence for potential clinical application of this flurbiprofen delivery system to better management of OA cases. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop poly( D, L-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles formulations for improved oral delivery of exemestane. Exemestane-loaded PLGA nanoparticles and PLGA/MMT nanoparticles were prepared by a modified solvent extraction/evaporation technology with vitamin E succinated polyethylene glycol 1000 (TPGS) as emulsifier. The content of MMT was estimated by thermal gravimetric analysis. The drug encapsulation efficiency and in vitro drug release kinetics were measured by high-performance liquid chromatography. The size, size distribution, surface charge and morphology of the exemestane-loaded nanoparticles were characterized using a Zetasizer Nano ZS and field emission scanning electron microscopy. The physical status of exemestane in the nanoparticles was characterized by differential scanning calorimetry. In vitro cellular uptake of coumarin-6-loaded nanoparticles was investigated by confocal laser scanning microscope, demonstrating that the fluorescence nanoparticles were internalized by Caco-2 cells (as an in vitro gastrointestinal model). The results of in vitro cytotoxicity experiment on MCF-7 cells (as a model of breast cancer cells) showed the exemestane-loaded nanoparticles resulted in lower cell viability versus the pure exemestane solution. The cytotoxicity against MCF-7 cells for exemestane-loaded nanoparticles and pure exemestane solution was dependent on the drug concentration and incubation time. In conclusion, this study indicates the capability of PLGA nanoparticles and PLGA/MMT nanoparticles in enhancing the oral delivery of exemestane. [ABSTRACT FROM AUTHOR]

[Display omitted] The aim of this investigation is to clarify the effect of D-α-tocopheryl succinate (vitamin E succinate, VES) and distearoylphosphatidyl ethanolamine-poly(ethylene glycol) (DSPE-PEG) on the encapsulation and controlled release of doxorubicin (DOX) in nano-assemblies and their consequences on the anti-tumor efficacy of DOX. DOX molecules were successfully loaded into the hybrid micelles with VES and DSPE-PEG (VDPM) via thin-film hydration method, exhibiting a small hydrodynamic particle size (~30 nm) and a weak negative zeta potential of around −5 mv. The obtained DOX-loaded VDPM2 displayed retarded DOX release at pH of 7.4, while substantially accelerated drug release at acidic pH of 5.0. Furthermore, the DOX-loaded VDPM2 exhibited substantially slower drug release rate at pH 7.4 compared with the drug-loaded VDPM1 or DPM preparation, benefiting for decreasing the premature DOX release during blood circulation. In vitro cell experiment indicated that DOX-loaded micelles (DPM, VDPM1 and VDPM2) improved the cellular uptake of DOX in 4T1 and MDA-MB-231 cells. The existence of VES component in the structure of DOX-loaded micelles had no obvious influence on the subcellular distribution of the encapsulated DOX molecules. Furthermore, the DOX-loaded VDPM2 exhibited more pronounced cytotoxicity to 4T1 and MDA-MB-231 cancerous cells compared with DOX-loaded DPM and free DOX solution. The hybrid nanocarriers including VES and DSPE-PEG selectively induced intracellular ROS accumulation and increased level of cytoplasmic calcium ion in cancerous cells by interacting with mitochondria and endoplasmic reticulum, bringing about the improved cytotoxicity of DOX. In vivo antitumor efficacy investigation of DOX-loaded VDPM2 against 4T1 xenograft-bearing mice displayed satisfied therapeutic activity with negligible systemic toxicity, as evidenced by the histological analysis and change of body weight. The proposed DOX-loaded VDPM preparation, as a mulifunctional chemotherapeutic nanomedicine system, holds great potential and bright prospect for clinical tumor therapy. [ABSTRACT FROM AUTHOR]