Immuno-Enhancing Effect of Ginsenoside Rh2 Liposomes on Foot-and-Mouth Disease Vaccine.

The adjuvant is essential for vaccines because it can enhance or directly induce a strong immune response associated with vaccine antigens. Ginsenoside Rh2 (Rh2) had immunomodulatory effects but was limited by poor solubility and hemolysis. In this study, Rh2 liposomes (Rh2-L) were prepared by ethanol injection methods. The Rh2-L effectively dispersed in a double emulsion adjuvant system to form a Water-in-Oil-in-Water (W/O/W) emulsion and had no hemolysis. The physicochemical properties of the adjuvants were tested, and the immune activity and auxiliary effects indicated by the Foot-and-Mouth disease (FMDV) antigen were evaluated. Compared with the mice vaccinated with the FMD vaccine prepared with the double emulsion adjuvant alone, those with the FMD vaccine prepared with the double emulsion adjuvant containing Rh2-L had significantly higher neutralizing antibody titer and splenocyte proliferation rates and showed higher cellular and humoral immune responses. The results demonstrated that Rh2-L could further enhance the immune effect of the double emulsion adjuvant against Foot-and-Mouth Disease.

PEGylated-PLGA Nanoparticles Coated with pH-Responsive Tannic Acid-Fe(III) Complexes for Reduced Premature Doxorubicin Release and Enhanced Targeting in Breast Cancer.

Biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been widely used as delivery vehicles for chemotherapy drugs. However, premature drug release in PLGA NPs can damage healthy tissue and cause serious adverse effects during systemic administration. Here, we report a tannic acid-Fe(III) (FeIII-TA) complex-modified PLGA nanoparticle platform (DOX-TPLGA NPs) for the tumor-targeted delivery of doxorubicin (DOX). A PEGylated-PLGA inner core and FeIII-TA complex outer shell were simultaneously introduced to reduce premature drug release in blood circulation and increase pH-triggered drug release in tumor tissue. Compared to the unmodified NPs, the initial burst rate of DOX-TPLGA NPs was significantly reduced by nearly 2-fold at pH 7.4. Moreover, the cumulative drug release rate at pH 5.0 was 40% greater than that at pH 7.4 due to the pH-response of the FeIII-TA complex. Cellular studies revealed that the TPLGA NPs had enhanced drug uptake and superior cytotoxicity of breast cancer cells in comparison to free DOX. Additionally, the DOX-TPLGA NPs efficiently accumulated in the tumor site of 4T1-bearing nude mice due to the enhanced permeability and retention (EPR) effect and reached a tumor inhibition rate of 85.53 ± 8.77% (1.31-fold versus DOX-PLGA NPs and 3.12-fold versus free DOX). Consequently, the novel TPLGA NPs represent a promising delivery platform to enhance the safety and efficacy of chemotherapy drugs.

Photothermal therapy enhance the anti-mitochondrial metabolism effect of lonidamine to renal cell carcinoma in homologous-targeted nanosystem.

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with poor prognosis. Therapeutic drugs for RCC can easily develop resistance or have unignorable toxicity or limited efficiency. Here, the thermosensitive mitochondrial metabolism-interfering anticancer drug lonidamine (LND) was combined with the photothermal material polydopamine (PDA) to treat RCC. To delivery drugs accurately to RCC site, LND and PDA were loaded in stellate mesoporous silica nanoparticles (MSNs) with a large surface area and cloaked with RCC membranes (MLP@M). The results showed that MLP@M exhibited excellent tumor targeting ability. The synergistic effects of LND and PDA in MLP@M were greatly enhanced when triggered by an 808 nm laser. Moreover, the antiproliferative and tumor suppressing abilities were enhanced with good biocompatibility after MLP@M + laser treatment. Additionally, 80% of RCC tumor-bearing mice treated with MLP@M + laser did not relapse. Our study provides a potential therapeutic approach for RCC treatment.

Screen for Inhibitors of Crystal Growth to Identify Desirable Carriers for Amorphous Solid Dispersions Containing Felodipine.

The solvent-shift method was used to identify appropriate polymers that inhibit the growth of felodipine crystals by monitoring particle size in supersaturated drug solutions in the presence of different polymers. We speculated that there would be an intermolecular interaction between the selected polymer (zein) and felodipine by extrapolating the inhibitory effect on crystal growth and then used the selected polymer as a carrier to prepare solid dispersions. The formulations were characterized by crystalline properties, thermodynamics of mixing, dissolution behavior, and physical stability. Powder x-ray diffraction and differential scanning calorimetry experiments indicated that amorphous solid dispersions were formed when the proportion of felodipine was < 30% (w/w). Stability tests showed that a solid dispersion with 20% felodipine remained in an amorphous state and was stable under accelerated storage conditions for 6 months. The dissolution rates of solid dispersions were significantly greater than those of the active pharmaceutical ingredient or physical mixtures. Analysis by Fourier-transform infrared spectroscopy and Raman microspectroscopy indicated the formation of intermolecular interactions between zein and felodipine. The study demonstrates the successful application of the chosen polymer as a carrier in solid dispersions and validates the concept of extrapolating the inhibitory effect on crystal growth to intermolecular interactions.

Characterization of ibuprofen microparticle and improvement of the dissolution.

The objective of this study was to prepare ibuprofen (IBP) microparticles by pH-change method and enhance the dissolution rate in vitro. Tween80 and Cremophor RH40 were selected as stabilizers to change the microparticles morphology. The microparticles were evaluated by dissolution profiles and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), laser particle size analyzer, scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). IBP microparticle prepared with surfactants showed a significant increase in dissolution rate (more than three times within 10 min) and an obvious decrease in mean particle size. The morphology of microparticles was obviously changed. XRD and DSC results revealed that the crystalline state of the untreated IBP and the prepared IBP microparticles were similar. The crystallinity of microparticles produced might be lightly reduced by adding surfactants in preparation process. All results showed that it was useful to prepare high dispersion microparticle by adding surfactants in the preparation process for improving the dissolution.

The Physicochemical Investigation of 17ß-Estradiol Crystalline Prepared by In Situ pH-Dependent Solubility Technique with Polyvinylpyrrolidone.

Micro-particles of 17ß-estradiol (ED) were prepared with polyvinylpyrrolidone (PVP) by in situ pH-dependent solubility technique. Products were characterized using multiple instruments, and molecular interactions between ED and PVP were explored. Powder X-ray diffraction and thermal analysis revealed crystalline ED in the micro-particles is hemihydrated. PVP was also present in the micro-particles. Laser particle size analysis and scanning electron microscopy revealed thin slice morphology, which might have resulted from the influence of PVP. Moreover, the results of contact angle, specific surface area, and dynamic vapor sorption showed that the surface properties of products were improved. These physicochemical properties of the micro-particles resulted in an obvious improvement in dissolution rate. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed hydrogen bonding between ED and PVP. A method was established for the preparation of micro-particles through the addition of PVP during the reaction process.

Module-combinatorial design and screening of multifunctional polymers based on polyaspartic acid for DNA delivery.

It is crucial to develop non-viral gene vectors that can efficiently and safely transfect plasmid DNA into cells. Low transfection efficiency and high cytotoxicity of cationic polymers hinder their application as gene carriers. Modification of cationic polymers has emerged as an attractive strategy for efficient and safe nucleic acids delivery. In this study, a simple and rapid method is developed to synthesize a series of multifunctional polymers by utilizing biodegradable polyaspartic acid as the backbone and modifying it with three modules. This one-component polymer possesses capabilities for nucleic acid condensation, cellular uptake, and endosomal escape. Polymers containing imidazole, triazole, or pyridine group exhibited promising transfection activity. Substituted with dodecylamine or 2-hexyldecan-1-amine enhance cellular uptake and subsequent transfection. Furthermore, the influence of ionizable amine side chains on gene delivery is investigated. Two optimal polymers, combined with the avian encephalomyelitis virus (AEV) plasmid vaccine, induced robust specific antibody responses and cellular immune responses in mice and chickens. Through module-combination design and screening of polyaspartamide polymers, this study presents a paradigm for the development of gene delivery vectors.

New self-nanoemulsifying drug delivery system (SNEDDS) with amphiphilic diblock copolymer methoxy poly (ethylene glycol)-block-poly (ε-caprolactone).

The objective of the study is to prepare a new self-nanoemulsifying drug delivery system (SNEDDS) with amphiphilic diblock copolymers methoxy poly (ethylene glycol)-block-poly (ε-caprolactone) (MPEG-b-PCL) and to investigate the effect of MPEG-b-PCL on the characteristics of SNEDDS. MPEG-b-PCL was synthesized and characterized by (1)H-NMR, IR and GPC. Various ratios of MPEG-b-PCL copolymers and Tween 80 were used as emulsifier to prepare the new SNEDDS. SNEDDS with high oil and low surfactant content forms a semi-solid gel at room temperature, which could be effectively sealed in soft or hard capsules. The mean droplet size of SNEDDS-generated nanoemulsions significantly decreased after the addition of diblock polymer and increased with increase of PCL chain in MPEG-b-PCL. The drug Coenzyme Q10 (CoQ10) was chosen as the model compound in this study due to its insolubility in water. CoQ10 from SNEDDS was rapidly dissolved regardless of the fluid condition.

PLGA-PEG-PLGA hydrogel for ocular drug delivery of dexamethasone acetate.

AIM: This study aims to investigate the suitability of thermosensitive triblock polymer poly-(DL-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA as a matrix material for ocular delivery of dexamethasone acetate (DXA). METHODS: The copolymer was synthesized and evaluated for its thermosensitive and gelation properties. DXA in situ gel-forming solution based on PLGA-PEG-PLGA copolymer of 20% (w/w) was prepared and evaluated for ocular pharmacokinetics in rabbit according to the microdialysis method, which was compared to the normal eye drop. RESULT: The copolymer with 20% (w/w) had a low critical solution temperature of 32 degrees C, which is close to the surface temperature of the eye. The C(max) of DXA in the anterior chamber for the PLGA-PEG-PLGA solution was 125.2 microg/mL, which is sevenfold higher than that of the eye drop, along with greater area under the concentration-time curves (AUC). CONCLUSION: These results suggest that the PLGA-PEG-PLGA copolymer is potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bioavailability, efficacy of some eye drugs.

A Novel Drug Delivery Carrier Comprised of Nimodipine Drug Solution and a Nanoemulsion: Preparation, Characterization, in vitro, and in vivo Studies.

PURPOSE: Nimodipine (NIMO) is used clinically to treat ischemic damage resulting from subarachnoid hemorrhage. However, clinical application of NIMO is limited by poor aqueous solubility and low safety. To overcome these limitations, a novel two-vial NIMO-loaded nanoemulsion (NIMO-TNE) was designed in this study. METHODS: NIMO-TNE was prepared by mixing a nimodipine-polyethylene glycol 400 (NIMO-PEG400) solution and a commercially available 20% injectable blank nanoemulsion (BNE). Drug distribution in NIMO-TNE, physical stability, and dilution stability were evaluated in vitro, and pharmacokinetics and pharmacodynamics were evaluated in vivo. Safety was assessed using the hemolysis test and the intravenous irritation test, and acute toxicity of NIMO-TNE was compared with that of commercial Nimotop injection. RESULTS: Drug loading (DL) in NIMO-TNE was enhanced 5-fold compared with that in Nimotop injection. The mean particle size of NIMO-TNE was 241.53 ± 1.48 nm. NIMO-TNE and NIMO-TNE diluted in 5% glucose injection and 0.9% sodium chloride was stable for a sufficient duration to allow for clinical use. In addition, NIMO-TNE exhibited a similar pharmacokinetic profile and similar brain ischemia reduction in a rat middle cerebral artery occlusion (MCAO) model compared to Nimotop injection. Furthermore, NIMO-TNE did not induce hemolysis at 37°C, and NIMO-TNE induced less intravenous irritation than Nimotop injection. Moreover, NIMO-TNE could be injected at a 23-fold higher dose than the LD50 of Nimotop injection with no obvious toxicity or side effects. CONCLUSION: NIMO-TNE is a promising formulation suitable for intravenous injection, is easy to prepare, and exhibits excellent safety.