Taste masking of water-soluble drug by solid lipid microspheres: a child-friendly system established by reversed lipid-based nanoparticle technique.

OBJECTIVES: A child-friendly taste-masking strategy using solid lipid microsphere (SLM) has been proposed to obscure the undesirable taste of some water-soluble drugs. In this study, the reversed lipid-based nanoparticle (RLBN) technique was used to encapsulate a water-soluble drug to facilitate the preparation of SLM. METHODS: The model drug used was atomoxetine hydrochloride (ATX), and a three-step method was used to prepare ATX-RLBN. Taste-masking microsphere (ATX-RLBN-SLM) was prepared by the spray chilling method. The drug release mechanism was studied by high-performance liquid chromatography and scanning electron microscopy. Moreover, in vitro taste evaluation method was established and ATX bioavailability was investigated employing pharmacokinetic studies. KEY FINDINGS: The obtained ATX-RLBN-SLM had smooth spherical particles with a size of about 80 µm. The drug encapsulation and loading efficiencies were 98.28% ± 0.59% and 0.89% ± 0.04%, respectively. In vitro drug release studies showed that nearly 96% drug was retained in the microspheres within 10 min at pH 6.8 and a complete release was triggered by lipase, accompanied by variation in the morphology. Taste assessment revealed that ATX-RLBN-SLM could efficiently mask the bitter taste and improved the bioavailability of ATX. CONCLUSIONS: Atomoxetine hydrochloride-reversed lipid-based nanoparticle-solid lipid microsphere exhibited excellent taste-masking effect with negligible leakage in the oral cavity environment and thorough collapse upon lipase stimulation, simultaneously enhancing the bioavailability of ATX. The study paves a new way to efficiently mask the undesirable taste of some water-soluble drugs.

Reversed Lipid-Based Nanoparticles Dispersed in Iodized Oil for Transarterial Chemoembolization.

Transarterial chemoembolization (TACE) is a promising treatment for patients suffering from unresectable liver malignancy. A coarse emulsion of doxorubicin solution and iodized oil is widely used in clinical practice. However, this coarse emulsion lacks sufficient physical stability and can split into water and oil very quickly. Furthermore, most chemotherapeutics are quickly released into systematic circulation, causing serious adverse effects. In this study, we aimed to prepare reversed lipid-based nanoparticles (RLBNs) dispersed in iodized oil as nanocarriers for the delivery of hydrophilic chemotherapeutics. Unlike a simple mixture of drug solution and oil, RLBN is a homogenous system and possesses a hydrophobic nanostructure that has high dispersibility in oils. Hydrophilic chemotherapeutics were entrapped in the polar core juxtaposed by highly biocompatible lipid materials, such as egg phospholipids. A sustained drug-release profile was observed in both in vitro and in vivo pharmacokinetics studies. The results of computed tomography showed that RLBN-doxorubicin-iodized oil could remain in the tumor region for more than 14 days and that the growth of tumors was effectively suppressed. Thus, the current results suggest that RLBN is a promising drug delivery system and is compatible with TACE treatment.

Protective Effect of Hydroxysafflor Yellow A on Inflammatory Injury in Chronic Obstructive Pulmonary Disease Rats.

OBJECTIVE: To investigate the attenuating effect of Hydroxysafflor yellow A (HSYA) on inflammatory injury in chronic obstructive pulmonary disease (COPD). METHODS: Rats were randomly assigned to 7 groups according to body weight including normal control group, HSYA blank group (76.8 mg/kg), COPD group, COPD+HSYA (30, 48, 76.8 mg/kg) groups and COPD+dexamethasone (2 mg/kg), 10 in each group. Passive cigarette smoke and intratracheal instillation of lipopolysaccharides were used to establish a COPD model in rats. Hematoxylin and eosin staining of lung tissue sections was used, real-time polymerase chain reaction (PCR) was used to assay mRNA levels of some cytokines in lung tissues, the cytokines in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA), Western blot analysis was used to determine phosphorylated p38 mitogen-activated protein kinase (MAPK) levels in lung tissues, and nuclear factor-κB (NF-κB) p65 protein levels in lung tissues were detected by immunohistochemistry. RESULTS: Lung alveolar septa destruction, alveolus fusion, inflammatory cell infiltration, and bronchiole exudation were observed. These pathological changes were alleviated in the COPD+HSYA group. The mRNA expression of inflammatory factors were significantly increased in lung tissues from COPD rats (all P<0.01) and were inhibited by HSYA. Levels of inflammatory cytokines in BALF of COPD rats were significantly increased (all P<0.01) which were inhibited by HSYA (all P<0.01, 48, 76.8 mg/kg). The levels of p38 MAPK phosphorylation and p65 in lung tissues of COPD rats were significantly increased (all P<0.01) and were suppressed by HSYA (all P<0.01, 48, 76.8 mg/kg). CONCLUSIONS: HSYA could alleviate inflammatory cell infiltration and other pathological changes in the lungs of COPD rats. HSYA inhibited inflammatory cytokine expression, and increase phosphorylation of p38 MAPK and NF-κB p65 in the lungs of COPD rats. The protective mechanism of HSYA to inhibit COPD inflammation might be by attenuating NF-κB and p38MAPK signal transduction.

[Understanding of the trigger points of myalgia: acupuncture and dry needling exploration and modern acupuncture mechanism].

The similarities and differences between trigger points of myalgia and acupoints were explored. Nodules could be detected by B-ultrasound at trigger points of myalgia, but not acupoints. In clinical symptoms, the referred pain pathway of trigger points of myalgia is similar with the pathway of acupuncture meridian. Therefore, the location of trigger points of myalgia should take referred pain as pathway, which is similar with locating acupoints as meridian. Acupuncture at trigger points of myalgia takes jumping feeling as criterion, while acupuncture at acupoints are mainly based on acid swelling and numbness. From clinical observation to basic experimental research, a lot of pathophysiological evidence is provided for trigger point of myalgia. It is believed that the trigger point of myalgia might be the precise acupoint in modern scientific research, and the meridian is the synthesis of the mechanics of nerve, blood vessel and fascia. Although acupuncture and dry needling are different in theory, but the scientific foundation of TCM and western medicine is coherent.

Hydroxysafflor Yellow A Alleviates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Mice.

Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L. The present study investigated the protective effect of HSYA on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in mice, and the underlying mechanisms involved. HSYA (14, 28, 56 mg/kg) was intraperitoneally injected to mice once daily from day 1 to 10 after LPS administration. HSYA attenuated the body weight loss, the augmented left index and the increase of pathologic changes in pulmonary inflammation caused by LPS. Treatment with HSYA also alleviated increased expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, transforming growth factor (TGF)-ß1, collagen (Col) I, Col III, α-smooth muscle actin (α-SMA), myeloid differentiation (MD)-2, Toll-like receptor 4 (TLR4) and cluster differentiation (CD)14 at the mRNA (RT-PCR) and protein levels (Western blot and enzyme-linked immuno sorbent assay). Moreover, HSYA inhibited the elevated levels of nuclear factor (NF)-κB and α-SMA in lung tissue (immunohistochemistry), and alleviated the slight collagen deposition in pulmonary tissues (Masson's trichrome staining). HSYA inhibited the specific binding of fluorescein isothiocyanate (FITC)-LPS on human lung epithelial cell line (A549) or human umbilical vein cell line (Eahy926) cells (flow cytometry). These findings suggested that HSYA has a protective effect on acute respiratory distress syndrome (ARDS) induced by LPS through blocking the TLR4/NF-κB pathway, and that the TLR4 receptor might be a target of HSYA on the cell membrane.