Targeted delivery of berberine using bionic nanomaterials for Atherosclerosis therapy.

Atherosclerosis (AS) is a prevalent chronic vascular inflammatory disease globally, initiated by injury to vascular endothelial cells (VECs). Macrophages play a pivotal role in disease pathogenesis, involving lipid metabolism and inflammation. The application of nanomaterials has been hindered by their rapid clearance by the immune system. Utilizing macrophage cell membranes can mitigate abnormal immune responses and induce a "homing" effect. Here, M2 macrophage cell membranes (M2) were coated onto berberine polylactic-hydroxylase-polylactide (PLGA) nanoparticles (BBR NPs), employing M2 macrophage immune escape, "homing" ability, and membrane coating nanotechnology, and loaded with mannose (Man) to create bionic nanoparticles (BBR NPs@Man/M2). Subsequently, the physical properties of BBR NPs@Man/M2 were characterized. The biocompatibility and biological function of BBR NPs@Man/M2 were assessed in vitro. Finally, the targeting, therapeutic efficacy, and safety of BBR NPs@M2 were investigated in an AS mouse model. The newly developed BBR NPs@Man/M2 exhibited good biocompatibility. Owing to their M2 coating, the nanoparticles effectively targeted macrophages in vitro, inducing a shift from a pro-inflammatory to an anti-inflammatory state. This transition reduced inflammation in endothelial cells and facilitated the repair of damaged endothelial cells. Moreover, M2-coated nanoparticles efficiently targeted and accumulated in atherosclerotic lesions in vivo. Following four weeks of treatment, BBR NPs@Man/M2 significantly delayed AS progression. Furthermore, BBR NPs@Man/M2 demonstrated a good safety profile after long-term administration. In conclusion, BBR NPs@Man/M2 effectively and safely inhibited AS progression. Biomimetic nanoparticles represent a promising approach for the safe and effective delivery of anti-AS drugs.

Wu H ，Zhang L ，Dong X ，Yang J ，Zheng L ，Li L ，Liu X ，Jin M ，Zhang P ... -  《-》

Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications.

Atherosclerosis (AS), the underlying cause of most cardiovascular events, is one of the most common causes of human morbidity and mortality worldwide due to the lack of an efficient strategy for targeted therapy. In this work, we aimed to develop an ideal biomimetic nanoparticle for targeted AS therapy. Methods: Based on macrophage "homing" into atherosclerotic lesions and cell membrane coating nanotechnology, biomimetic nanoparticles (MM/RAPNPs) were fabricated with a macrophage membrane (MM) coating on the surface of rapamycin-loaded poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (RAPNPs). Subsequently, the physical properties of the MM/RAPNPs were characterized. The biocompatibility and biological functions of MM/RAPNPs were determined in vitro. Finally, in AS mouse models, the targeting characteristics, therapeutic efficacy and safety of the MM/RAPNPs were examined. Results: The advanced MM/RAPNPs demonstrated good biocompatibility. Due to the MM coating, the nanoparticles effectively inhibited the phagocytosis by macrophages and targeted activated endothelial cells in vitro. In addition, MM-coated nanoparticles effectively targeted and accumulated in atherosclerotic lesions in vivo. After a 4-week treatment program, MM/RAPNPs were shown to significantly delay the progression of AS. Furthermore, MM/RAPNPs displayed favorable safety performance after long-term administration. Conclusion: These results demonstrate that MM/RAPNPs could efficiently and safely inhibit the progression of AS. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications.

Wang Y ，Zhang K ，Li T ，Maruf A ，Qin X ，Luo L ，Zhong Y ，Qiu J ，McGinty S ，Pontrelli G ，Liao X ，Wu W ，Wang G ... -  《Theranostics》

Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer's disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood-brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid β42 (Aβ42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3β/GSK3β, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aβ42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aβ42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.

Saleh SR ，Abd-Elmegied A ，Aly Madhy S ，Khattab SN ，Sheta E ，Elnozahy FY ，Mehanna RA ，Ghareeb DA ，Abd-Elmonem NM ... -  《-》

Micro- and Nanoencapsulated Hybrid Delivery System (MNEHDS): A Novel Approach for Colon-Targeted Oral Delivery of Berberine.

Zhang L ，Li M ，Zhang G ，Gao C ，Wang S ，Zhang T ，Ma C ，Wang L ，Zhu Q ... -  《-》

The inhibitory effect of PLGA-encapsulated berberine on hepatotoxicity and α-smooth muscle actin (α-SMA) gene expression.

Liver injury results in excessive extracellular matrix (ECM) deposition in the liver, which is mainly produced by hepatic stellate cells (HSC). Alpha-smooth muscle actin (α-SMA) and liver enzymes are the two hallmarks of liver injury. Previously, it has been confirmed that berberine (BBR) attenuates liver injury. This study aimed to investigate the protective effect of Poly Lactic-co-Glycolic Acid (PLGA) encapsulated BBR against liver injury. Nanoprecipitation, encapsulation, and physio-chemical characterization of BBR-PLGA nanoparticles (BBR-PLGA-NP) have been done. The protective effects of BBR-PLGA-NPs and BBR against carbon tetrachloride (CCl4)-treated Wistar rats were investigated. The serum levels of alanine aminotransferase and aspartate transaminase were measured, and the expression level of α-SMA was quantified by qRT-PCR. To evaluate the liver changes, morphological and histological staining was done. BBR-PLGA-NPs markedly reduced serum ALT and AST in rats treated with CCl4. Although the expression level of α-SMA was downregulated in the CCl4-injected rats that were treated with BBR, α-SMA expression in this group was still remarkably higher than the control group. α-SMA mRNA was significantly under-expressed (p < 0.05) by BBR-PLGA-NPs and the hepatic histology revealed BBR-PLGA-NPs made further improvements than free BBR. The use of nanoparticle to encapsulate BBR is a worthy approach to enhance the curative effect of BBR against liver injuries, which donate a safe and effective drug delivery strategy to treat liver injuries.

Ahrari A ，Najafzadehvarzi H ，Taravati A ，Tohidi F ... -  《-》