Nanovehicles For Delivery Research Articles

Biopolymer Nanovehicles for Oral Delivery of Natural Anticancer Agents (Adv. Funct. Mater. 4/2023)

Natural Anticancer Agents Cancer is the second leading cause of death throughout the world. In article number 2209419, Hadis Rostamabadi and co-workers, comprehensively overview the biopolymer nanovehicles for oral delivery of natural anticancer agents (NAAs). NAAs that are a gift of nature to humanity, have been extensively utilized in alleviation/prevention of cancer. The oral delivery of NAAs is restricted by some inherent features (e.g., poor solubility, low bioavailability, etc.). Nano-driven encapsulation strategies via natural polymers are potent carriers for safe delivery of NAAs.

Synthesis and Characterization of Innovative Microgels Based on Polyacrylic Acid and Microalgae Cell Wall and Their Potential as Antigen Delivery Vehicles.

In this study, hybrid polyacrylic acid and Schizochytrium sp. microalgae (PAA/Schizo) microgels were synthesized by inverse emulsion assisted by ultrasound using the cell wall fraction as crosslinker. Physicochemical characterization of PAA/Schizo microgels revealed polymeric spherical particles (288 ± 39 nm) and were deemed stable and negatively charged. The produced microgels are not inherently toxic as cell viability was sustained above 80% when mice splenocytes were exposed to concentrations ranging 10-900 µg/mL. PAA/Schizo microgels were evaluated as antigen delivery nanovehicle by adsorbing bovine serum albumin (BSA); with a loading efficiency of 72% and loading capacity of 362 µg/mg. Overall, intranasally-immunized BALB/c mice showed null IgG or IgA responses against PAA/Schizo microgel-BSA, whereas soluble BSA induced significant humoral responses in systemic and mucosal compartments. Splenocytes proliferation assay upon BSA stimulus revealed positive CD4+ T cells-proliferation response in PAA/Schizo microgels-BSA group. Thus, PAA/Schizo microgels constitute functional antigen delivery vehicles of simple and ecofriendly synthesis. Moreover, the use of cell wall fraction as cross-linker agent provides an alternative use for the generation of high-value products using residual algae biomass from the oil industry. Our data suggests that the PAA/Schizo microgels are potential antigen delivery vehicles for immunotherapy development.

Biopolymer Nanovehicles for Oral Delivery of Natural Anticancer Agents

AbstractCancer is the second leading cause of death throughout the world. Nature‐inspired anticancer agents (NAAs) that are a gift of nature to humanity have been extensively utilized in the alleviation/prevention of the disease due to their numerous pharmacological activities. While the oral route is an ideal and common way of drug administration, the application of NAAs through the oral pathway has been extremely limited owing to their inherent features, e.g., poor solubility, gastrointestinal (GI) instability, and low bioavailability. With the development of nano‐driven encapsulation strategies, polymeric vehicles, especially those with natural origins, have demonstrated a potent platform, which can professionally shield versatile NAAs against GI barricades and safely deliver them to the site of action. In this review, the predicament of orally delivering NAAs and the encapsulation strategy solutions based on biopolymer matrices are summarized. Proof‐of‐concept in vitro/in vivo results are also discussed for oral delivery of these agents by various biopolymer vehicles, which can be found so far from the literature. Last but not the least, the challenges and new opportunities in the field are highlighted.

Engineering polymer nanoparticles using cell membrane coating technology and their application in cancer treatments: Opportunities and challenges

Nanotechnology has revolutionized cancer drug delivery, and recent research continues to focus on the development of “one-size- fits-all,” i.e., “all-in-one” delivery nanovehicles. Although nanomedicines can address significant shortcomings of conventional therapy, biological barriers remain a challenge in their delivery and accumulation at diseased sites. To achieve long circulation time, immune evasion, and targeted accumulation, conventional nanocarriers need modifications, e.g., PEGylation, peptide/aptamer attachment, etc. One such modification is a biomimetic coating using cell membrane (CM), which can offer long circulation or targeting, or both. This top-down CM coating process is facile and can provide some advantageous features over surface modification by synthetic polymers. Herein, an overview is provided on the engineering of CM camouflaged polymer nanoparticles. A short section on CM and the development of CM coating technology has been provided. Detailed description of the preparation and characterization of CM camouflaged polymer NPs and their applications in cancer treatment has been reported. A brief comparison between CM coating and PEGylation has been highlighted. Various targeting approaches to achieve tumor-specific delivery of CM coated NPs have been summarized here. Overall, this review will give the readers a nice picture of CM coated polymer NPs, along with their opportunities and challenges.

Lipid Nanoparticles: Promising Treatment Approach for Parkinson's Disease.

Parkinson’s disease (PD), a neurodegenerative disorder, is a life-altering, debilitating disease exhibiting a severe physical, psychological, and financial burden on patients. Globally, approximately 7–10 million people are afflicted with this disease, with the number of cases estimated to increase to 12.9 million by 2040. PD is a progressive movement disorder with nonmotor symptoms, including insomnia, depression, anxiety, and anosmia. While current therapeutics are available to PD patients, this treatment remains palliative, necessitating alternative treatment approaches. A major hurdle in treating PD is the protective nature of the blood–brain barrier (BBB) and its ability to limit access to foreign molecules, including therapeutics. Drugs utilized presently are nonspecific and administered at dosages that result in numerous adverse side effects. Nanomedicine has emerged as a potential strategy for treating many diseases. From the array of nanomaterials available, lipid nanoparticles (LNPs) possess various advantages, including enhanced permeability to the brain via passive diffusion and specific and nonspecific transporters. Their bioavailability, nontoxic nature, ability to be conjugated to drugs, and targeting moieties catapult LNPs as a promising therapeutic nanocarriers for PD. While PD-related studies are limited, their potential as therapeutics is evident in their formulations as vaccines. This review is aimed at examining the roles and properties of LNPs that make them efficient therapeutic nanodelivery vehicles for the treatment of PD, including therapeutic advances made to date.

Self-fluorescence property of octa-arginine functionalized hydroxyapatite nanoparticles aids in studying their intracellular fate in R1 ESCs

Deciphering the endocytosis mechanisms of nanoparticle entry in cells is crucial to understand the fate of nanoparticles and the biological activity of the transported cargo. Such studies require the use of reporter agents such as fluorescent markers. Previously, we have reported the synthesis of self-fluorescent HAp nanoparticles as efficient nucleic acid delivery agents in prokaryotic and eukaryotic cells. Here, we show the application of biocompatible self-fluorescent nano delivery vehicle based on HAp and CPP- octa-arginine as an efficient system to study the mechanisms of intracellular fate of a gene delivery agent. The pathway of octa-arginine functionalized HAp NP (R8HNP) and HAp NP uptake in R1 ESCs was elucidated using confocal microscopy with the help of endocytic inhibitors. The NPs mainly enter R1 ESCs by clathrin mediated and macropinocytosis pathways. It was established that the NPs escape endosomal degradation by proton sponge effect owing to their ability to buffer the pH and trigger osmotic rupture. The functionalization of CPP, effectively enhanced the internalization and endosomal escape in R1 ESCs. The detailed results of these studies are outlined in this manuscript.

Biointerface engineering of self-protective bionic nanomissiles for targeted synergistic chemotherapy

Erythrocyte membrane (EM)-camouflaged chemotherapeutic delivery nanovehicles hold promise for solid tumor therapy because of their excellent biostability and biocompatibility. However, it is accompanied with insufficient targeting effect and deficient pharmacokinetic behavior due to the lack of a regulated biointerface to navigate and overcome biological transportation obstacles in solid tumor therapy. Herein, an anti-epidermal growth factor receptor (EGFR) aptamer (EApt) modified and EM-cloaked chemotherapeutic nanomissile delivery system was constructed. The anchored-EApt acting as a specific EGFR suppressor promotes to inhibit the overexpression of EGFR and initiate the cell apoptosis. Importantly, the resulting PLGA-DOX@EM-EApt orchestrated the bioactivity of each component and provided synergistic cell apoptosis and antitumor effects by precisely suppressing EGFR expression levels and delivering DOX. The in vitro and in vivo experimental results confirmed that the immune escape and active targeting behaviors of PLGA-DOX@EM-EApt could significantly promote its drug retention and tumor inhibition abilities. Our findings propose a novel strategy using the biointerface functionalization technique, demonstrating a promising therapeutic platform via a biomimetic drug delivery system for precise solid tumor recognition and synergistic therapy.

Tumor-Microenvironment-Activated NIR-II Nanotheranostic Platform for Precise Diagnosis and Treatment of Colon Cancer.

Rational design of tumor-microenvironment (TME)-activated nanoformulation for precisely targeted cancer treatment has recently attracted an enormous attention. However, the all-in-one TME-activated theranostic nanosystems with a simple preparation and high biocompatibility are still rarely reported. Herein, catalase nanocrystals (CatCry) are first introduced as a tumor microenvironment activatable nanoplatform for selective theranostics of colon cancer. They are engaged as (i) a "nanoreactor" for silver nanoparticles (AgNP) synthesis, (ii) a nanovehicle for tumor delivery of anticancer drug doxorubicin (DOX), and (iii) an in situ O2 generator to relief tumor hypoxia. When CatCry-AgNP-DOX nanoformulation is within a tumor, the intratumoral H2S turns AgNP into Ag2S nanoparticles, inducing a photothermal effect and NIR-II emission under 808 nm laser irradiation and also triggering DOX release. Simultaneously, CatCry catalyzes intratumoral H2O2 into O2, relieving hypoxia and enhancing chemotherapy. In contrast, when delivered to healthy tissue without increased concentration of H2S, the developed nanoformulation remains in the "off" state and no theranostic action takes place. Studies with colon cancer cells in vitro and a murine colon cancer model in vivo demonstrated that CatCry-AgNP-DOX delivered a synergistic combination of PTT and enhanced chemotherapy, enabling complete eradication of tumor with minimal side effects. This work not only introduces nanoplatform for theranostics of H2S-rich tumors but also suggests a general strategy for protein-crystal-based nanomedicine.

Preparation and Characterization of a Novel Mucoadhesive Carvedilol Nanosponge: A Promising Platform for Buccal Anti-Hypertensive Delivery.

Carvedilol (CRV) is a non-selective third generation beta-blocker used to treat hypertension, congestive heart failure and angina pectoris. Oral administration of CRV showed poor bioavailability (25%), which might be ascribed to its extensive first-pass metabolism. Buccal delivery is known to boost drugs bioavailability. The aim of this study is to investigate the efficacy of bilosomes-based mucoadhesive carvedilol nanosponge for enhancing the oral bioavailability of CRV. The bilosomes were prepared, optimized and characterized for particle size, surface morphology, encapsulation efficiency and ex-vivo permeation studies. Then, the optimized formula was incorporated into a carboxymethyl cellulose/hydroxypropyl cellulose (CMC/HPC) composite mixture to obtain buccal nanosponge enriched with CRV bilosomes. The optimized bilosome formula (BLS9), showing minimum vesicle size, maximum entrapment, and highest cumulative in vitro release, exhibited a spherical shape with 217.2 nm in diameter, 87.13% entrapment efficiency, and sustained drug release for up to 24 h. In addition, ex-vivo drug permeation across sheep buccal mucosa revealed enhanced drug permeation with bilosomal formulations, compared to aqueous drug suspension. Consecutively, BLS9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain bilosomal nanosponge to enhance CRV buccal delivery. Morphological analysis of the prepared nanosponge revealed improved swelling with a porosity of 67.58%. The in vivo assessment of rats indicated that CRV-loaded nanosponge efficiently enhanced systolic/diastolic blood pressure, decreased elevated oxidative stress, improved lipid profile and exhibited a potent cardio-protective effect. Collectively, bilosomal nanosponge might represent a plausible nanovehicle for buccal delivery of CRV for effective management of hypertension.

Curcumin-Induced Stabilization of Protein-Based Nano-Delivery Vehicles Reduces Disruption of Zwitterionic Giant Unilamellar Vesicles.

Curcumin-loaded native and succinylated pea protein nanoparticles, as well as zwitterionic giant unilamellar vesicles were used in this study as model bioactive compound loaded-nanoparticles and biomembranes, respectively, to assess bio-nano interactions. Curcumin-loaded native protein-chitosan and succinylated protein-chitosan complexes, as well as native protein-chitosan and succinylated protein-chitosan hollow, induced leakage of the calcein encapsulated in the giant unilamellar vesicles. The leakage was more pronounced with hollow protein-chitosan complexes. However, curcumin-loaded native protein and curcumin-loaded succinylated protein nanoparticles induced calcein fluorescence quenching. Dynamic light scattering measurements showed that the interaction of curcumin-loaded native protein, curcumin-loaded succinylated protein, native protein-chitosan, and succinylated protein-chitosan complexes with the giant unilamellar vesicles caused a major reduction in the size of the lipid vesicles. Confocal and widefield fluorescence microscopy showed rupturing of the unilamellar vesicles after treatment with native pea protein-chitosan and succinylated pea protein-chitosan complexes. The nature of interaction between the curcumin-loaded protein nanoparticles and the biomembranes, at the bio-nano interface, is influenced by the encapsulated curcumin. Findings from this study showed that, as the protein plays a crucial role in stabilizing the bioactive compound from chemical and photodegradation, the encapsulated nutraceutical stabilizes the protein nanoparticle to reduce its interaction with biomembranes.

Poly(N-vinylpyrrolidone)-block-Poly(dimethylsiloxane)-block-Poly(N-vinylpyrrolidone) Triblock Copolymer Polymersomes for Delivery of PARP1 siRNA to Breast Cancers.

Nearly 20% of HER2-positive breast cancers develop resistance to HER2-targeted therapies requiring the use of advanced therapies. Silencing RNA therapy may be a powerful modality for treating resistant HER2 cancers due to its high specificity and low toxicity. However, the systemic administration of siRNAs requires a safe and efficient delivery platform because of siRNA's low stability in physiological fluids, inefficient cellular uptake, immunoreactivity, and rapid clearance. We have developed theranostic polymeric vesicles to overcome these hurdles for encapsulation and delivery of small functional molecules and PARP1 siRNA for in vivo delivery to breast cancer tumors. The 100 nm polymer vesicles were assembled from biodegradable and non-ionic poly(N-vinylpyrrolidone)14-block-poly(dimethylsiloxane)47-block-poly(N-vinylpyrrolidone)14 triblock copolymer PVPON14-PDMS47-PVPON14 using nanoprecipitation and thin-film hydration. We demonstrated that the vesicles assembled from the copolymer covalently tagged with the Cy5.5 fluorescent dye for in vivo imaging could also encapsulate the model drug with high loading efficiency (40%). The dye-loaded vesicles were accumulated in tumors after 18 h circulation in 4TR breast tumor-bearing mice via passive targeting. We found that PARP1 siRNA encapsulated into the vesicles was released intact (13%) into solution by the therapeutic ultrasound treatment as quantified by gel electrophoresis. The PARP1 siRNA-loaded polymersomes inhibited the proliferation of MDA-MB-361TR cells by 34% after 6 days of treatment by suppressing the NF-kB signaling pathway, unlike their scrambled siRNA-loaded counterparts. Finally, the treatment by PARP1 siRNA-loaded vesicles prolonged the survival of the mice bearing 4T1 breast cancer xenografts, with the 4-fold survival increase, unlike the untreated mice after 3 weeks following the treatment. These biodegradable, non-ionic PVPON14-PDMS47-PVPON14 polymeric nanovesicles capable of the efficient encapsulation and delivery of PARP1 siRNA to successfully knock down PARP1 in vivo can provide an advanced platform for the development of precision-targeted therapeutic carriers, which could help develop highly effective drug delivery nanovehicles for breast cancer gene therapy.

Effect and Mechanism of the Lenvatinib@H-MnO2-FA Drug Delivery System in Targeting Intrahepatic Cholangiocarcinoma.

To investigate the effects of the Lenvatinib@H-MnO2-FA administration system on the proliferation and apoptosis of Intrahepatic cholangiocarcinoma (ICC) and the underlying molecular mechanism. In this research, hollow MnO2 (H-MnO2) was synthesized via the modified Stöber method, and H-MnO2 was modified with polyethylene glycol-bis (Amine) (NH2-PEG-NH2) and folic acid (FA) to obtain H-MnO2-PEG-FA (H-MnO2-FA). Lenvatinib was coated in the hollow cavity of H-MnO2-PEG-FA to further form a nanometre drug-carrying system (Lenvatinib@H-MnO2-PEG-FA). Lenvatinib@H-MnO2-FA was characterized through transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FT-IR) was used to verify that Lenvatinib was loaded on nanoparticles. Functionally, confocal laser scanning microscopy (CLSM), 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine the effect of Lenvatinib@H-MnO2-FA on the proliferation and apoptosis of ICC cells (9810 cells). Finally, the protein levels of Raf-1MEK1/2-ERK1/2 signalling pathway components were detected through Western blotting analysis. We successfully synthesised a Lenvatinib@H-MnO2-PEG-FA administration system. The resulting nanomaterials had excellent biological stability and improved targeting effects. Functionally, Lenvatinib@ H-MnO2-FA inhibited the proliferation of 9810 cells. The Bcl-2 protein level was significantly downregulated, and the caspase-3 protein level was significantly upregulated, indicating that Lenvatinib@H-MnO2- PEG- FA promoted the apoptosis of 9810 cells. Mechanistically, Lenvatinib@H-MnO2-FA increased the phosphorylation levels of Raf, MEK1/2, and ERK1/2. H-MnO2-FA can more effectively deliver Lenvatinib to inhibit proliferation and promote apoptosis in ICC, which could be the promising drug delivery nano-vehicles for delivery drugs.

Lipid nanoparticles for delivery of RNA therapeutics: Current status and the role of in vivo imaging.

Lipid nanoparticles (LNPs) have been one of the most successful nano-delivery vehicles that enable efficient delivery of cytotoxic chemotherapy agents, antibiotics, and nucleic acid therapeutics. During the coronavirus disease (COVID-19) pandemic, LNP-based COVID-19 messenger RNA (mRNA) vaccines from Pfizer/BioNTech and Moderna have been successfully developed, resulting in global sales of $37 billion and $17.7 billion, respectively, in 2021. Based on this success, the development of multiple LNP-based RNA therapeutics is gaining momentum due to its potential in vaccines and therapeutics for various genetic diseases and cancers. Furthermore, imaging techniques can be utilized to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) effects, which helps target discovery and accelerates the development of LNP-based mRNA therapies. A thorough introduction and explanation of the components of LNPs and its functions along with various production methods of formulating LNPs are provided in this review. Furthermore, recent advances in LNP-based RNA therapeutics in clinics and clinical trials are explored. Additionally, the evaluation of PK/PD of LNPs for RNA delivery and the current and potential roles in developing LNP-based mRNA pharmaceutics through imaging techniques will be discussed.

Cluster of D-maltose clicked to β-cyclodextrin: preparation and its application as a biocompatible drug delivery nanovehicle

ABSTRACT In the current study, it was tried to design and synthesize a new derivative of β-cyclodextrin (β-CD) as a result of reaction with D-maltose (β-CD-M) to compare and investigate its capability as an anticancer drug nanocarrier. The success in the β-CD-M synthesis was validated via common characterization techniques: nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The SEM results indicate that the obtained β-CD-M molecule has a crystalline structure with a size of less than 100 nm. In the following, methotrexate (MTX) and doxorubicin (DOX) as the model of anticancer drugs were separately loaded in β-CD-M and their release profile was obtained. The outcome of the cytotoxic assay against MCF 10A cells indicated that β-CD-M is biocompatible and could be used as a drug carrier. Overall, from the obtained results, the synthesized biocompatible β-CD-M with more drug loading capacity and a controlled release profile in comparison to unmodified β-CD could be proposed as a potential nanocarrier for anticancer drug delivery.

Glycosylated zein as a novel nanodelivery vehicle for lutein

Glucosamine-glycosylated zein (GLZ) generated by transglutaminase was developed as a novel delivery vehicle to prepare lutein-loaded glycosylated zein nanoparticles (GLZ-LUT). GLZ-LUT exhibited a polydispersed spherical microstructure, lutein was embedded into GLZ to form nanocomplexes via self-assembly, they had a lower zeta potential and an average particle size of less than 200 nm. Compared to lutein-loaded zein nanoparticles (Zein-LUT), the lutein entrapment efficiency of GLZ-LUT was increased from 81.55% to 89.60%. Infrared spectroscopy (FTIR) analysis results confirmed that zein was successfully modified and that lutein was encapsulated by hydrophobic zein and GLZ. Moreover, GLZ showed significantly higher solubilization of lutein than Zein-LUT and significantly improved the in vitro release of lutein in the simulated gastrointestinal tract. The in vitro antioxidant activity of lutein was also enhanced by the encapsulation of zein and glycosylated zein. These findings indicated that GLZ represent a potentially efficient and promising nanodelivery carrier for lutein compounds.

Targetable nano-delivery vehicles to deliver anti-bacterial small acid-soluble spore protein (SASP) genes.

Interest in phage-based therapeutics is increasing, at least in part due to the need for new treatment options for infections caused by antibiotic-resistant bacteria. It is possible to use wild-type (WT) phages to treat bacterial infections, but it is also possible to modify WT phages to generate therapeutics with improved features. Here, we will discuss features of Phico Therapeutics' SASPject technology, which modifies phages for use as targetable nano-delivery vehicles (NDV), to introduce antibacterial Small Acid Soluble Spore Protein (SASP) genes into specific target bacteria.

PH low insertion peptide (pHLIP)-decorated polymeric nanovehicle for efficient and pH-responsive siRNA translocation

As a hallmark of most solid tumors, tumor acidic microenvironment aids tumor survival and progression. Tumor acidity also represents a tumor-specific stimulus that has been harnessed for the design and development of pH-responsive drug delivery systems. Pyruvate kinase M2 (PKM2) functions as an oncoprotein in tumorigenesis, and its overexpression in many tumors promotes metabolic rewiring towards aerobic glycolysis. Herein, a pH low insertion peptide (pHLIP)-functionalized copolymer of polyethylenimine and polylactide (pHLIP-PEI-PLA) was synthesized and self-assembled into a pH-responsive nanovehicle for delivery of siRNA to specifically target PKM2, a rate-limiting enzyme in glycolysis. The delivery of siPKM2 by pHLIP-decorated polymeric nanovehicle sufficiently downregulated the expression of PKM2 and exhibited potent inhibition on HepG2 cell migration. We believe that this strategy of targeting glycolysis-associated PKM2 gene by tumor acidity-responsive RNAi nanovehicle may offer a potential means for anticancer therapy.

An Overview of Gadolinium-Based Oxide and Oxysulfide Particles: Synthesis, Properties, and Biomedical Applications

In the last decade, the publications presenting novel physical and chemical aspects of gadolinium-based oxide (Gd2O3) and oxysulfide (Gd2O2S) particles in the micro- or nano-scale have increased, mainly stimulated by the exciting applications of these materials in the biomedical field. Their optical properties, related to down and upconversion phenomena and the ability to functionalize their surface, make them attractive for developing new probes for selective targeting and emergent bioimaging techniques, either for biomolecule labeling or theranostics. Moreover, recent reports have shown interesting optical behavior of these systems influenced by the synthesis methods, dopant amount and type, particle shape and size, and surface functionality. Hence, this review presents a compilation of the latest works focused on evaluating the optical properties of Gd2O3 and Gd2O2S particles as a function of their physicochemical and morphological properties; and also on their novel applications as MRI contrast agents and drug delivery nanovehicles, discussed along with their administration routes, biodistribution, cytotoxicity, and clearance mechanisms. Perspectives for this field are also identified and discussed.

Evaluating the mucoprotective effects of glycyrrhizic acid-loaded polymeric nanoparticles in a murine model of 5-fluorouracil-induced intestinal mucositis via suppression of inflammatory mediators and oxidative stress.

5-Fluorouracil (5-FU), a chemotherapeutic drug, has severe deteriorating effects on the intestine, leading to mucositis. Glycyrrhizic acid is a compound derived from a common herbal plant Glycyrrhiza glabra, with mucoprotective, antioxidant and anti-inflammatory actions, however, associated with poor pharmacokinetics. Owing to the remarkable therapeutic action of glycyrrhizic acid-loaded polymeric nanocarriers in inflammatory bowel disease, we explored their activity against 5-FU-induced intestinal mucositis in mice. Polymeric nanocarriers have proven to be efficient drug delivery vehicles for the long-term treatment of inflammatory diseases, but have not yet been explored for 5-FU-induced mucositis. Therefore, this study aimed to produce glycyrrhizic acid-loaded polylactic-co-glycolic acid (GA-PLGA) nanoparticles to evaluate their protective and therapeutic effects in a 5-FU-induced mucositis model. GA-PLGA nanoparticles were prepared using a modified double emulsion method, physicochemically characterized, and tested for in vitro drug release. Thereafter, mucositis was induced by 5-FU (50mg/kg; IP) administration to the mice for the first 3 days (day 0, 1, 2), and mice were treated orally with GA-PLGA nanoparticles for 7 days (day 0-6). GA-PLGA nanoparticles significantly reduced mucositis severity measured by body weight, diarrhea score, distress, and anorexia. Further, 5-FU induced intestinal histopathological damage, altered villi-crypt length, reduced goblet cell count, elevated pro-inflammatory mediators, and suppressed antioxidant enzymes, all of which were reversed by GA-PLGA nanoparticles. Morphological, behavioral, histological, and biochemical results suggested that GA-PLGA nanoparticles were efficient, biocompatible, targeted, and sustained release drug delivery nano-vehicle for enhanced mucoprotective, anti-inflammatory, and antioxidant effects in 5-FU-induced intestinal mucositis.

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex.

BackgroundGlioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.MethodsHere, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.ResultsThe particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and −15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.ConclusionOur study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.