A new perspective on gut-lung axis affected through resident microbiome and their implications on immune response in respiratory diseases.

The highly diverse microbial ecosystem of the human body colonizes the gastrointestinal tract has a profound impact on the host's immune, metabolic, endocrine, and other physiological processes, which are all interconnected. Specifically, gut microbiota has been found to play a crucial role in facilitating the adaptation and initiation of immune regulatory response through the gastrointestinal tract affecting the other distal mucosal sites such as lungs. A tightly regulated lung-gut axis during respiratory ailments may influence the various molecular patterns that instructs priming the disease severity to dysregulate the normal function. This review provides a comprehensive summary of current research on gut microbiota dysbiosis in respiratory diseases including asthma, pneumonia, bronchopneumonia, COPD during infections and cancer. A complex-interaction among gut microbiome, associated metabolites, cytokines, and chemokines regulates the protective immune response activating the mucosal humoral and cellular response. This potential mechanism bridges the regulation patterns through the gut-lung axis. This paper aims to advance the understanding of the crosstalk of gut-lung microbiome during infection, could lead to strategize to modulate the gut microbiome as a treatment plan to improve bad prognosis in various respiratory diseases.

New insights into nanotherapeutics for periodontitis: a triple concerto of antimicrobial activity, immunomodulation and periodontium regeneration.

Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends.

Preparation, characterisation, pharmacokinetics and distribution of esculin microspheres administered via intravitreal injection into rabbit brain.

This study explored the distribution of esculin microspheres in rabbit brain tissue following intravitreal injection and investigated the possibility of direct entry of the drug into the brain through the eye, to develop a formulation with enhanced therapeutic efficacy against Parkinson's disease.Chitosan microspheres of esculin were prepared via an emulsification cross-linking method and their characteristics were evaluated, including angle of repose, bulk density, and swelling ratio. Furthermore, the pharmacokinetic parameters and brain tissue distribution in rabbits were compared among groups administered esculin eye drops, intravitreal esculin solution, and intravitreal esculin microspheres, to determine whether esculin could enter the brain through an ocular route.The results showed that the prepared esculin microspheres were spherical and had good fluidity. Notably, intravitreal administration enhanced the area under the curve (AUC) of esculin in the thalamus. Delivery through microspheres prolonged the drug retention time in both rabbit plasma and brain tissues, as well as the brain-targeting efficiency of esculin.The collective findings indicated that there may be a direct eye-brain pathway facilitating enter of esculin microspheres into brain tissue after intravitreal injection, supporting the utility of intravitreal esculin microspheres as an effective therapeutic formulation for Parkinson's disease, a long-term chronic condition.

Design and Evaluation of Ophthalmic Thermosensitive In Situ Gel of Compound Salvia.

The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses.

[Metabolite identification and metabolic pathway analysis of Platycodonis Radix extracts from Tongcheng city in rats].

In this study, we delved into the prototypical components and metabolites of Platycodonis Radix extracts(PRE) from Tongcheng city in plasma, urine and feces of rats, and revealed its metabolic pathways and metabolic rules in vivo. The prototypical components and metabolites of PRE in rats were characterized and identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and mass defect filter(MDF). The biological samples were analyzed by ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm), with 0.1% formic acid water(A)-0.1% formic acid acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). Twelve prototypical saponins and twenty-seven metabolites were detected in plasma, urine and feces of rats treated with PRE by oral administration. Eleven prototypical components and nine metabolites were detected in plasma, eleven prototypical components and eight metabo-lites were detected in urine, and ten prototypical components and twenty metabolites were detected in feces. Further studies showed that the metabolic pathways of PRE in rats mainly include oxidation, reduction, acetylation, stepwise hydrolytic deglycosylation, glucuronidation and so on. This study provides a scientific basis for clarifying the pharmacological basis and mechanism of PRE from Tongcheng city.

Identification and functional characterization of two trans-isopentenyl diphosphate synthases and one squalene synthase involved in triterpenoid biosynthesis in Platycodon grandiflorus.

MAIN CONCLUSION: Two trans-isopentenyl diphosphate synthase and one squalene synthase genes were identified and proved to be involved in the triterpenoid biosynthesis in Platycodon grandiflorus. Platycodon grandiflorus is a commonly used traditional Chinese medicine. The main bioactive compounds of P. grandiflorus are triterpenoid saponins. The biosynthetic pathway of triterpenoid saponins in P. grandiflorus has been preliminarily explored. However, limited functional information on related genes has been reported. A total of three trans-isopentenyl diphosphate synthases (trans-IDSs) genes (PgFPPS, PgGGPPS1 and PgGGPPS2) and one squalene synthase (SQS) gene (PgSQS) in P. grandiflorus were screened and identified from transcriptome dataset. Subcellular localization of the proteins was defined based on the analysis of GFP-tagged. The activity of genes was verified in Escherichia coli, demonstrating that recombinant PgFPPS catalysed the production of farnesyl diphosphate. PgGGPPS1 produced geranylgeranyl diphosphate, whereas PgGGPPS2 did not exhibit catalytic activity. By structural identification of encoding genes, a transmembrane region was found at the C-terminus of the PgSQS gene, which produced an insoluble protein when expressed in E. coli but showed no apparent effect on the enzyme function. Furthermore, some triterpenoid saponin synthesis-related genes were discovered by combining the component content and the gene expression assays at the five growth stages of P. grandiflorus seedlings. The accumulation of active components in P. grandiflorus was closely associated with the expression level of genes related to the synthesis pathway.

Microemulsion-thermosensitive gel composites as in situ-forming drug reservoir for periodontitis tissue repair through alveolar bone and collagen regeneration strategy.

A satisfactory clinical effect in treating periodontitis is often difficult to achieve by conventional non-surgical systemic drug delivery due to the narrow anatomical structure of the periodontal pocket and insufficient drug concentration at lesion sites. In addition, the feasibility of combating periodontal tissue lesions by restoring the alveolar bone and allowing collagen regeneration has not been fully explored. The objective of this study was to prepare a microemulsion integrating the anti-inflammatory and osteogenic active ingredients of baicalin and clove oil (BC-MEs). Then, the composite hydrogel obtained by mixing poloxamer 407 and 188 was used as the thermosensitive gel matrix to load BC-MEs and form a drug reservoir (Gel-BC-MEs) injectable in situ. Gel-BC-MEs exhibited a significant, sustained release of baicalin for 12 h, gelation temperature was 33.4 ± 0.36 °C, and pH was 5.45 ± 0.12. The experiment on a rat periodontitis model demonstrated that Gel-BC-MEs significantly improved periodontal tissue repair by collagen regeneration and osteogenesis by inhibiting osteoclast infiltration. This study proposes a novel strategy for periodontal tissue repair by enhancing the therapeutic potential of a microemulsion using an in situ nano-gel delivery system.

SAR study culminates in a series of HDAC6 selective inhibitors featuring Schisandrin C-analogous Cap as potential immunomodulatory agents for cancer therapy.

HDAC6 inhibitors (HDAC6is) represent an emerging therapeutic option for triggering anti-cancer immune response. In this work, a novel series of HDAC6is, derived from an in-house analog of the traditional Chinese medicine monomer Schisandrin C, were designed and synthesized for SAR study. Throughout the 29 target compounds, 24a, 24b and 24h exerted single-digit nanomolar enzymatic activity and remarkably elevated subtype selectivity compared to the clinically investigated HDAC6i Ricolinostat (Selectivity index = 3.3). In A549 tumor cells, 24h, as the representative in this series (IC50 = 7.7 nM; selectivity index = 31.4), was capable of reversing IL-6-mediated PD-L1 upregulation, highlighting its immunomodulatory capability. Importantly, unlike numerous other hydroxamate-based HDACis, 24h displayed an acceptable oral bioavailability in Sprague-Dawley rats, along with high plasma exposure, long elimination half-life and slow clearance. With the aforementioned attractive performance, 24h deserves further in vivo investigation as an immunomodulatory therapeutic agent for batting human malignance.

Sorafenib-Loaded PLGA-TPGS Nanosystems Enhance Hepatocellular Carcinoma Therapy Through Reversing P-Glycoprotein-Mediated Multidrug Resistance.

Multidrug resistance (MDR) is a key determinant for hepatocellular carcinoma chemotherapy failure. P-glycoprotein is one of the main causes of MDR by causing drug efflux in tumor cells. In order to solve this thorny problem, we prepared a sorafenib-loaded polylactic acid-glycolic acid (PLGA) - D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (SPTNs). SPTNs were successfully synthesized through an ultrasonic emulsion solvent evaporation method with a favourable encapsulation efficiency of 90.35%. SPTNs were almost spherical in shape with uniform particle size (215.70 ± 0.36 nm), narrow polydispersity index (0.27 ± 0.02) and negative surface charge (-26.01 ± 0.65 mV). In the cellular uptake assay, the intracellular coumarin-6 (C6) fluorescence of TPGS component-based PLGA nanoparticles (C6-PTNs) was 1.63-fold higher relative to that of PVA component-based PLGA nanoparticles (C6-PVNs). The half-maximal inhibitory concentration and apoptosis ratio of SPTNs against HepG2/MDR cells were 3.90 µM and 75.62%, respectively, which were notably higher than free SF and sorafenib-PLGA-PVA nanoparticles (SPVNs). The anti-drug efflux activities of SPTNs were assessed by the intracellular trafficking assay using verapamil as a P-gp inhibitor. SPTNs could effectively inhibit the drug efflux in tumor cells detected by flow cytometry, and suppressed relative MDR1 gene as well as P-glycoprotein expression in tumor cells. Attributed to the MDR reversion effect of SPTNs, the in vivo antitumor efficacy experiment showed that SPTNs significantly inhibited the tumor growth of HepG2/MDR xenograft-bearing nude mice, and obviously reduced the toxicity against liver and kidney compared with SF treatment. In summary, SPTNs, as highly efficient and safe antitumor nano delivery systems, showed promising potential for hepatocellular carcinoma therapy through reversing P-glycoprotein-mediated MDR. Graphical Abstract.

Smart Nanogatekeepers for Tumor Theranostics.

Nanoparticulate drug delivery systems (nano-DDSs) are required to reliably arrive and persistently reside at the tumor site with minimal off-target side effects for clinical theranostics. However, due to the complicated environment and high interstitial pressure in tumor tissue, they can return to the bloodstream and cause secondary side effects in normal organs. Recently, a number of nanogatekeepers have been engineered via structure-transformable/stable strategies to overcome this undesirable dilemma. The emerging structure-transformable nanogatekeepers for tumor imaging and therapy are first overviewed here, particularly for nanogatekeepers undergoing structural transformation in tumor microenvironments, cell membranes, and organelles. Thereafter, intelligent structure-stable nanogatekeepers through reversible activation and artificial individualization receptors are overviewed. Finally, the ongoing challenges and prospects of nanogatekeepers for clinical translation are briefly discussed.

Transcriptome analysis identifies putative genes involved in triterpenoid biosynthesis in Platycodon grandiflorus.

MAIN CONCLUSION: Comprehensive transcriptome analysis of different Platycodon grandiflorus tissues discovered genes related to triterpenoid saponin biosynthesis. Platycodon grandiflorus (Jacq.) A. DC. (P. grandiflorus), a traditional Chinese medicine, contains considerable triterpenoid saponins with broad pharmacological activities. Triterpenoid saponins are the major components of P. grandiflorus. Here, single-molecule real-time and next-generation sequencing technologies were combined to comprehensively analyse the transcriptome and identify genes involved in triterpenoid saponin biosynthesis in P. grandiflorus. We quantified four saponins in P. grandiflorus and found that their total content was highest in the roots and lowest in the stems and leaves. A total of 173,354 non-redundant transcripts were generated from the PacBio platform, and three full-length transcripts of ß-amyrin synthase, the key synthase of ß-amyrin, were identified. A total of 132,610 clean reads obtained from the DNBSEQ platform were utilised to explore key genes related to the triterpenoid saponin biosynthetic pathway in P. grandiflorus, and 96 differentially expressed genes were selected as candidates. The expression levels of these genes were verified by quantitative real-time PCR. Our reliable transcriptome data provide valuable information on the related biosynthesis pathway and may provide insights into the molecular mechanisms of triterpenoid saponin biosynthesis in P. grandiflorus.

Pueraria flavones-loaded bile salt liposomes with improved intestinal absorption and oral bioavailability: in vitro and in vivo evaluation.

Pueraria flavone (PF), the main component of Pueraria lobata, is a traditional Chinese medicine used for the treatment of cardiovascular and cerebrovascular diseases; however, it exhibits low oral bioavailability because of its poor membrane permeability. In this study, PF-loaded sodium deoxycholate-decorated liposomes (SDC-Lips) were prepared using the reverse-phase evaporation method and optimised using the Box-Behnken design method. The morphology, particle size, zeta potential, and entrapment efficiency of these PF-loaded SDC-Lips were evaluated. The release behaviours of PF-loaded SDC-Lips in simulated gastric and intestinal fluids were consistent with the Weibull kinetic model. In situ intestinal perfusion studies showed that the absorption characteristics of free PF in rats were mainly passive diffusion and partly active transport, and the duodenum was the main absorption site. After encapsulated with SDC-Lips, the absorption of PF increased significantly. The in vivo pharmacokinetic parameters of area under the plasma concentration-time curve (AUC)(0 → 12 h) and AUC(0 → ∞) of PF-loaded SDC-Lips after intragastric administration were 1.34-fold and 1.543-fold, respectively. Overall, the PF-loaded SDC-Lips improved the oral absorption of PF by increasing its solubility and might be considered a promising formulation strategy for prolonging the biological activity time of PF.

Transdermal Administration of Ibuprofen-Loaded Gel: Preparation, Pharmacokinetic Profile, and Tissue Distribution.

The purpose of this study was to compare the pharmacokinetics and tissue distribution of ibuprofen (IBU) gel in female rats after transdermal administration through the skin of the abdomen and back. IBU was used as the model drug to prepare carbomer gel. After the abdominal and back administration, the concentration of IBU in rat plasma was detected by high-performance liquid chromatography (HPLC). Besides, the contents of IBU in the uterus, heart, liver, spleen, lung, and kidney were detected, respectively, to clarify the distribution characteristics in vivo. Through abdominal route, the AUC0- ∞ (area under the concentration-time curve from time zero to infinity) of uterus was 424.75 µg/g h, which is 3.60 times higher than that of plasma, and was significantly higher than that of other tissues (P < 0.0001). Tmax (peak time) of uterus and plasma was 4 h and 2 h, respectively. Upon transdermal application of IBU to the back, the AUC0-∞ of uterus was 75.47 µg/g h, which is 12.63 times lower than that of plasma, while Tmax of uterus and plasma was not lower than 20 h. These results indicated that IBU entered the blood circulation through abdominal administration in a small amount and mainly of the drug entered the uterus, while IBU entered the blood circulation and redistributed to tissues after absorption through the dorsal skin slowly. IBU could effectively reach the uterus and have a certain targeting through abdominal administration, which provides a prospect for clinical transdermal administration in the treatment of dysmenorrhea.

[Evolution of commercial specification and experimental identification terms of Gastrodiae Rhizoma].

Gastrodia Rhizoma, as a precious Chinese materia medica, has attracted the attention of Chinese materia medica experts in the past dynasties for the commercial specification and experimental identification, and has gradually formed a wealth of terms concerning commercial specification and experimental identification. Through combing the literatures of successive dynasties, this paper discussed the change of the commercial specification of the Gastrodiae Rhizoma and formation of its identifying terms. It has found that the Gastrodiae Rhizoma mainly came from the dried rhizomes of the Gastrodia elata f.elata before the Qing Dynasty. Since the Qing Dynasty, G. elata in Yunnan and Guizhou gradually arose and become one of sources of mainstream commodities. After that, G. elata f. glauca and G. elata f. elata were becoming the main sources of Gastrodiae Rhizoma. Before the large-scale cultivation of G. elata in the 1970 s, there is only wild G. elata over the country. In terms of commercial specification, they were often classified into Chunma and Dongma according to their harvest time. With the successful promotion of cultivation technology and the endangered wild resources of G. elata, the Dongma became the mainstream in the market. The adulterants of G. elata increased significantly in the 1960 s and 1970 s, in this period, the terms of experimental identification for G. elata also increased obviously. Experimental identification is distinctive in different times, therefore, studying experimental identification of medicinal materials helps to promote the development of the Chinese materia medica.

Dual drug-loaded cubic liquid crystal gels for transdermal delivery: inner structure and percutaneous mechanism evaluations.

The goal of this paper was to develop and evaluate dual component-loaded with the hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) cubic liquid crystal gels for transdermal delivery. The gels was prepared with a vortex method using phytantriol/water (70:30, w/w) and characterized by polarized light microscopy, small-angle X-ray scattering and rheology. The inner structure of the gels were Pn3m cubic phase and exhibited a pseudoplastic fluid behavior. Furthermore, the in vitro release profile showed that the release behavior of the two drugs from cubic liquid crystal gels conformed to Higuchi equation and were dominated by Fick's diffusion (n < 0.45). The ex vivo penetration experiment indicated that dual components-loaded liquid crystal gels can enhance and extend the skin permeation of these two drugs, especially the ratio of SH to CA is 1: 0.5. Finally, transdermal mechanisms were evaluated using laser scanning confocal microscopy and attenuated total reflectance-fourier transform infrared, hinting that hydrophilic and lipophilic drugs weaken each other's transdermal velocity at the initial stage of penetration. In short, the dual drug-loaded liquid crystal gels was a promising strategy for transdermal applications in treatment of chronic disease.

A Novel Phytantriol-Based Lyotropic Liquid Crystalline Gel for Efficient Ophthalmic Delivery of Pilocarpine Nitrate.

The purpose of this paper was to investigate the potential of liquid crystalline (LC) gels for ophthalmic delivery, so as to enhance the bioavailability of pilocarpine nitrate (PN). The gels were prepared by a vortex method using phytantriol and water (in the ratio of 73:27 w/w). Their inner structures were confirmed by crossed polarized light microscopy, small-angle X-ray scattering, attenuated total reflectance-Fourier transform infrared spectrum, and rheology. The in vitro release studies revealed that PN could keep sustained release from the gels over a period of 12 h. The ex vivo apparent permeability coefficient of the gels demonstrated a 3.83-folds (P < 0.05) increase compared with that of eye drops. The corneal hydration levels of the gel maintained in the normal range of 79.46 ± 2.82%, hinting that the gel could be considered non-damaging and safe to the eyes. Furthermore, in vivo residence time evaluation suggested that a better retention performance of LC gel was observed in rabbit's eyes compared to eye drops. In vivo ocular irritation study indicated that LC gel was nonirritant and might be suitable for various eye applications. In conclusion, LC gels might represent a potential ophthalmic delivery strategy to overcome the limitations of eye drops.

Enhanced stability of vitamin A palmitate microencapsulated by γ-cyclodextrin metal-organic frameworks.

γ-Cyclodextrin metal-organic frameworks (γ-CD-MOFs) are highly porous and bio-friendly novel materials formed by γ-CD as an organic ligand and potassium ion as an inorganic metal centre. The aim of this study was to enhance the stability of vitamin A palmitate (VAP) using γ-CD-MOFs as the carrier. Herein, γ-CD-MOFs displayed VAP microencapsulating capacity of 9.77 ± 0.24% with molar ratio as nMOFs:nVAP = 3.2:1.0. It was important to find that the improved stability of VAP microencapsulated by γ-CD-MOFs without addition of any antioxidant(s) was better than that of the best available reference product in the market, with 1.6-fold elongated half-life. The protecting mechanism of γ-CD-MOFs for VAP contributed that VAP molecules preferentially curled inside the cavities of dual γ-CD pairs in γ-CD-MOFs. It was proved that γ-CD-MOFs were an efficient new carrier to deliver and protect VAP for food and pharmaceutical applications.

Quantitative and Chemical Fingerprint Analysis for the Quality Evaluation of Platycodi Radix Collected from Various Regions in China by HPLC Coupled with Chemometrics.

Platycodi Radix (PR) is the root of Platycodon grandiflorum (Jacq.) A. DC., which has been used for a long time in China to treat pulmonary diseases. The present study aimed to evaluate the quality of PR samples collected from 23 regions of 11 provinces in China. Eight saponins were quantified using HPLC coupled with evaporative light scattering detection (HPLC-ELSD). The samples with the highest total contents of saponins were from southern China, such as Yunnan, Guangxi, Jiangxi, and Guangzhou. The fingerprint analysis of PR samples was conducted by HPLC-UV method. Nineteen common peaks were selected and the similarity values varied from 0.607 to 0.921. These findings indicated that the saponins contents of PR from different regions varied significantly, with PR samples from southern China having the highest contents of saponins. These comprehensive methods were successful in evaluating the quality of PR samples from northern and southern China, which will serve as a guide for the development of PR as a clinical medication.

Development and Evaluation of Minocycline Hydrochloride-Loaded In Situ Cubic Liquid Crystal for Intra-Periodontal Pocket Administration.

In the present study, an injectable in situ liquid crystal formulation was developed for local delivery of minocycline hydrochloride (MH) for chronic periodontitis treatment. The physicochemical properties, phase structures, in vitro drug release and pharmacodynamics of in situ liquid crystals were investigated. The optimal formulation (phytantriol (PT)/propylene glycol (PG)/water, 63/27/10, w/w/w) loaded with 20 mg/g MH was proved to be injectable. The precursor formulation can form a cubic phase gel in excess water in 6.97 ± 0.10 s. The results of in vitro drug release suggested the MH presented a sustained release for 4 days. Liquid crystal precursor formulation significantly reduced gingival index, probing depth and alveolar bone loss compared to the model group (p < 0.01). Besides, the pathological characteristics of model rats were improved. The results suggested that MH-loaded in situ cubic liquid crystal possessed of sustained release ability and periodontal clinical symptoms improvement. The developed in situ cubic liquid crystal may be a potentially carrier in the local delivery of MH for periodontal diseases.

Characterization and In Vitro Permeation Study of Cubic Liquid Crystal Containing Sinomenine Hydrochloride.

This study developed a new transdermal delivery system for the improved delivery of sinomenine hydrochloride (SH). The delivery system utilized the advantages of lyotropic liquid crystals (LLC) creating an adaptable system that offers a variety of options for the field of transdermal delivery. The formulation was prepared, characterized, and evaluated for its skin penetration in vitro. In the study, the appearance of samples was characterized by visual observation, and these LLC gels were colorless and transparent. Polarizing light microscopy (PLM) and small-angle X-ray diffraction (SAXS) were used to analyze the internal structures of gels, and the gels displayed a cubic double-diamond (Pn3m) internal structure with a dark field of vision. The Franze diffusion cell was used to evaluate its skin penetration. There were several factors which might influence the skin penetration of drugs, such as drug loading, water content, and the layer spacing of the LLC. In our case, drug concentration gradient played a more powerful role. The result of in vitro permeation studies demonstrated that the drug concentration was higher; the cumulative osmotic quantity of SH (Q) was greater. Therefore, the system was a promising formulation for successful percutaneous delivery of SH through the skin.