Pharmacokinetics of 10-hydroxycamptothecin-tetrandrine liposome complexes in rat by a simple and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry.

10-Hydroxycamptothecin is a drug to cure various cancers. However, the 10-hydroxycamptothecin cannot be widely applied in clinics due to fast elimination and resistance of various cancers to the drug. Nevertheless, co-treatment with tetrandine is known to reverse the resistance of multi-drug resistant cancers, and may present an effective strategy to improve the efficacy of 10-hydroxycamptothecin. In order to improve the bioavailability and prolong the treatment time of the 10-hydroxycamptothecin in vivo, we prepared 10-hydroxycamptothecin-tetrandrine liposome complexes with 10-hydroxycamptothecin as the basic anticancer drug, tetrandrine and liposomes as carriers. In this article, an ultra-high performance liquid chromatography tandem mass spectrometry method for the analysis of 10-hydroxycamptothecin and tetrandrine in plasma has been developed, validated, and utilized to compare the pharmacokinetics of both drugs in the original dosage form and administered as liposome complexes. According to the pharmacokinetic parameters of mean residence time, half-life period and clearance rate, the 10-hydroxycamptothecin-tetrandrine liposome complexes prolongs the retention and circulation time of 10-hydroxycamptothecin in vivo, achieving a good sustained release effect. To the best of our current knowledge, the pharmacokinetic properties of 10-hydroxycamptothecin-tetrandrine liposome complexes in rats have not been reported yet. Our study can provide a helpful reference for further related study.

Study on the stabilization mechanisms of wet-milled cepharanthine nanosuspensions using systematical characterization.

Objectives: Stability issues are inevitable problems that are encountered in nanosuspension (NS) technology developments and in the industrial application of pharmaceuticals. This study aims to assess the stability of wet-milled cepharanthine NSs and elucidate the stabilization mechanisms of different stabilizers.Methods: The aggregation state was examined via scanning electron microscopy, laser diffraction, and rheometry. The zeta potential, stabilizer adsorption, surface tension, and drug-stabilizer interactions were employed to elucidate the stabilization mechanisms.Results: The results suggest that croscarmellose sodium (CCS), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), or polyvinyl pyrrolidone VA64 (PVP VA64) alone was able to prevent nanoparticle aggregation for at least 30 days. Attempts to evaluate the stability mechanisms of different stabilization systems revealed that CCS improved the steric-kinetic stabilization of the NSs, attributed to its high viscosity, swelling capacity, and physical barrier effects. In contrast, the excellent physical stability of TPGS systems was mainly due to the reduced surface tension and higher crystallinity. PVP VA64 can adsorb onto the surfaces of nanoparticles and stabilize the NS via steric forces.Conclusion: This study demonstrated the complex effects of CCS, TPGS, and PVP VA64 on cepharanthine NS stability and presented an approach for the rational design of stable NSs.

[Preparation and in vitro evaluation of tetrandrine-loaded composite microspheres embedded with PLGA nanoparticles].

In this paper, we prepared a type of composite microspheres embedded with poly (lactic-co-glycolic acid) (PLGA) nanoparticles for efficient inhalation delivery of tetrandrine (Tet), which is a traditional Chinese medicine for anticancer, and studied its morphology, drug release profile, cytotoxicity and cellular uptake behavior. PLGA nanoparticles loading tetrandrine were prepared by emulsion solvent diffusion method, and composite microspheres were prepared by spray drying method with mannitol as matrix due to its osmotic effect. Scanning electronic microscopy, dynamic light scattering laser particle analyzer and confocal microscopy were applied to characterize the morphology and size of the microspheres. The drug loading rate, drug encapsulation efficiency and drug release properties were explored by RP-HPLC. The cytotoxicity in A549 cells between crude drug of Tet and Tet-loaded microspheres were compared by MTT assay. The cellular uptake behavior of microspheres in A549 cells was investigated using confocal laser scanning microscopy. The resultant microspheres were composed of 189 nm PLGA nanoparticles exhibited sizes ranging from 1 to 3 µm, with the highest deposition efficiency. The microspheres can easily be dissolved in a mimic lung environment and release redispersible PLGA nanoparticles. Compared with crude drug of Tet, Tet-loaded microspheres showed a certain sustained release property and higher cytotoxicity effect to A549 cells. The cellular uptake experiment demonstrated a higher excellent penetration ability of cells to nanoparticles and time-dependent uptake process. This study provides a basis for developing new inhalation therapies for lung cancer.

[Studies on preparation by SPG membrane emulsification method and in vitro characterization of tetradrine-tashionone II(A)-PLGA composite microspheres].

Tetradrine-tashionone II(A)-PLGA composite microspheres were prepared by the SPG membrane emulsification method, and the characterization of tetradrine-tashionone II(A) -PLGA composite microspheres were studied in this experiment. The results of IR, DSC and XRD showed that teradrine and tashionone II(A) in composite microspheres were highly dispersed in the PLGA with amorphous form. The results of tetradrine-tashionone II(A) -PLGA composite microspheres in vitro release experiment showed that the cumulative release amounts of tetradrine and tashionone II(A) were 6.44% and 3.60% in 24 h, and the cumulative release amounts of tetradrine and tashionone II(A) were 89.02% and 21.24% in 17 d. The process of drug in vitro release accorded with the model of Riger-Peppas. Tetradrine-tashionone II(A) -PLGA composite microspheres had slow-release effect, and it could significantly reduce the burst release, prolong the therapeutic time, decrease the dosage of drugs and provide a new idea and method to prepare traditional Chinese medicine compound.

[Preparation and characterization of tetrandrine-loaded PLGA nanocomposite particles by premix membrane emulsification coupled with spray-drying method].

For effective inhalable dry-powder drug delivery, tetrandrine-PLGA (polylactic-co-glycolic acid) nanocomposite particles have been developed to overcome the disadvantages of nanoparticles and microparticles. The primary nanoparticles were prepared by using premix membrane emulsification method. To prepare second particles, they were spray dried. The final particles were characterized by scanning electron microscopy (SEM), dry laser particle size analysis, high performance liquid chromatography (HPLC), X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared analysis (IR) and confocal laser scanning microscope (CLSM). The average size of the primary particles was (337.5 ± 6.2) nm, while that second particles was (3.675 ± 0.16) µm which can be decomposed into primary nanoparticles in water. And the second particles were solid sphere-like with the drug dispersed as armorphous form in them. It is a reference for components delivery to lung in a new form.

Structural analysis of a ligand-triggered intermolecular disulfide switch in a major latex protein from opium poppy.

Several proteins from plant pathogenesis-related family 10 (PR10) are highly abundant in the latex of opium poppy and have recently been shown to play diverse and important roles in the biosynthesis of benzylisoquinoline alkaloids (BIAs). The recent determination of the first crystal structures of PR10-10 showed how large conformational changes in a surface loop and adjacent ß-strand are coupled to the binding of BIA compounds to the central hydrophobic binding pocket. A more detailed analysis of these conformational changes is now reported to further clarify how ligand binding is coupled to the formation and cleavage of an intermolecular disulfide bond that is only sterically allowed when the BIA binding pocket is empty. To decouple ligand binding from disulfide-bond formation, each of the two highly conserved cysteine residues (Cys59 and Cys155) in PR10-10 was replaced with serine using site-directed mutagenesis. Crystal structures of the Cys59Ser mutant were determined in the presence of papaverine and in the absence of exogenous BIA compounds. A crystal structure of the Cys155Ser mutant was also determined in the absence of exogenous BIA compounds. All three of these crystal structures reveal conformations similar to that of wild-type PR10-10 with bound BIA compounds. In the absence of exogenous BIA compounds, the Cys59Ser and Cys155Ser mutants appear to bind an unidentified ligand or mixture of ligands that was presumably introduced during expression of the proteins in Escherichia coli. The analysis of conformational changes triggered by the binding of BIA compounds suggests a molecular mechanism coupling ligand binding to the disruption of an intermolecular disulfide bond. This mechanism may be involved in the regulation of biosynthetic reactions in plants and possibly other organisms.

Tumor-Targeted cRGD-Coated Liposomes Encapsulating Optimized Synergistic Cepharanthine and IR783 for Chemotherapy and Photothermal Therapy.

Background: Combination therapy offers superior therapeutic results compared to monotherapy. However, the outcomes of combination therapy often fall short of expectations, mainly because of increased toxicity from drug interactions and challenges in achieving the desired spatial and temporal distribution of drug delivery. Optimizing synergistic drug combination ratios to ensure uniform targeting and distribution across space and time, particularly in vivo, is a significant challenge. In this study, cRGD-coated liposomes encapsulating optimized synergistic cepharanthine (CEP; a chemotherapy drug) and IR783 (a phototherapy agent) were developed for combined chemotherapy and photothermal therapy in vitro and in vivo. Methods: An MTT assay was used to evaluate the combination index of CEP and IR783 in five cell lines. The cRGD-encapsulated liposomes were prepared via thin-film hydration, and unencapsulated liposomes served as controls for the loading of CEP and IR783. Fluorescence and photothermal imaging were used to assess the efficacy of CEP and IR783 encapsulated in liposomes at an optimal synergistic ratio, both in vitro and in vivo. Results: The combination indices of CEP and IR783 were determined in five cell lines. As a proof-of-concept, the optimal synergistic ratio (1:2) of CEP to IR783 in 4T1 cells was evaluated in vitro and in vivo. The average diameter of the liposomes was approximately 100 nm. The liposomes effectively retained the encapsulated CEP and IR783 in vitro at the optimal synergistic molar ratio for over 7 d. In vivo fluorescence imaging revealed that the fluorescence signal from cRGD-CEP-IR783-Lip was detectable at the tumor site at 4 h post-injection and peaked at 8 h. In vivo photothermal imaging of tumor-bearing mice indicated an increase in tumor temperature by 32°C within 200 s. Concurrently, cRGD-CEP-IR783-Lip demonstrated a significant therapeutic effect and robust biosafety in the in vivo antitumor experiments. Conclusion: The combination indices of CEP and IR783 were successfully determined in vitro in five cell lines. The cRGD-coated liposomes encapsulated CEP and IR783 at an optimal synergistic ratio, exhibiting enhanced antitumor effects and targeting upon application in vitro and in vivo. This study presents a novel concept and establishes a research framework for synergistic chemotherapy and phototherapy treatment.

Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats.

The blood-brain barrier (BBB) and multidrug resistance (MDR) are the main causes for poor prognosis of glioma patients after chemotherapy. To explore the way for settling this problem, in this study, a novel antitumor agent loaded drug delivery system, lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine (Lf-PO-Dox/Tet), integrating both BBB and glioma-targeting moiety and MDR inhibitor, was designed and its chemotherapy for glioma rats was evaluated. Biodegradable polymersome (PO) encapsulating both doxorubicin (Dox) and tetrandrine (Tet) was prepared by the thin-film hydration method (PO-Dox/Tet) and then conjugated with lactoferrin (Lf) to yield Lf-PO-Dox/Tet with an average diameter around 220 nm and surface Lf molecule number per polymersome around 40. Compared with PO-DOX, PO-Dox/Tet, and Lf-PO-Dox, Lf-PO-Dox/Tet demonstrated the strongest cytotoxicity against C6 glioma cells and the greatest uptake index by C6 cells. In vivo imaging analysis indicated that Lf-PO labeled with a near-infrared dye could enter the brain and accumulate at the tumor site. Pharmacokinetics and tissue distribution results also showed that Lf-PO-Dox/Tet accumulated more in the right hemisphere than other groups of polymersomes. Pharmacodynamics results revealed that tumor volume of the Lf-PO-Dox/Tet group was significantly smaller than that of other therapeutic groups, and the median survival time of Lf-PO-Dox/Tet group was longer than that of Lf-PO-Dox group and significantly longer than those of the other three therapeutic groups. These results suggested that Lf-PO-Dox/Tet could have therapeutic potential for gliomas.

A novel controlled release tetrandrine-loaded PDLLA film: evaluation of drug release and anti-adhesion effects in vitro and in vivo.

To investigate the drug release and anti-adhesion effects of a TET (tetrandrine)-loaded PDLLA (poly-DL-lactide) film. Detection of TET release in vitro was carried out by high-performance liquid chromatography (HPLC) every 2 days following immersion of the tetrandrine-loaded PDLLA film in simulated body fluid until the TET content of the eluate could not be detected. For the in vivo test, TET-loaded PDLLA films were implanted into animal laminectomy models and positive and blank control groups were also set up. Postoperative serum tests, and macroscopic and histological analyses at 1, 4, 8, and 12 weeks, were used to assess the effects of the film. Statistical analyses were performed by one-way ANOVA. The drug release of the tetrandrine-loaded PDLLA film in vitro showed two phases with a second release peak. Ultimately, the duration of continuous delivery was up to 66 days and the cumulative delivery rate was up to 93.18%. Scores for the proliferation of epidural scars or adhesion of the dura mater in the test group were much lower than those for the two control groups. Histological analysis revealed the test group had fewer inflammatory cells and fibroblasts, as well as fewer extracellular collagen fibers, and a lower histology score than those of the two control groups at all time points. Tetrandrine-loaded PDLLA film is a novel controlled drug release and anti-adhesion material in vitro and in vivo.

Intranasal tetrandrine temperature-sensitive in situ hydrogels for the treatment of microwave-induced brain injury.

The brain is the most sensitive organ to microwave radiation. However, few effective drugs are available for the treatment of microwave-induced brain injury due to the poor drug permeation into the brain. Here, intranasal tetrandrine (TET) temperature-sensitive in situ hydrogels (ISGs) were prepared with poloxamers 407 and 188. Its characteristics were evaluated, including rheological properties, drug release in vitro, and mucosal irritation. The pharmacodynamics and brain-targeting effects were also studied. The highly viscous ISGs remained in the nasal cavity for a long time with the sustained release of TET and no obvious ciliary toxicity. Intranasal temperature-sensitive TET ISGs markedly improved the spatial memory and spontaneous exploratory behavior induced by microwave with the Morris water maze (MWM) and the open field test (OFT) compared to the model. The ISGs alleviated the microwave-induced brain damage and inhibited the certain mRNA expressions of calcium channels in the brain. Intranasal temperature-sensitive TET ISGs was rapidly absorbed with a shorter Tmax (4.8 h) compared to that of oral TET (8.4 h). The brain targeting index of intranasal temperature-sensitive TET ISGs was as 2.26 times as that of the oral TET. Intranasal temperature-sensitive TET ISGs are a promising brain-targeted medication for the treatment of microwave-induced brain injury.

[Preparation of tetrandrine alginate calcium sustained release gel pellets].

OBJECTIVE: To prepare tetrandrine alginate calcium sustained release gel pellets twice daily with Eudragit RS 30D and Eudragit RL 30D. METHODS: The sustained release gel pellets were prepared by fluid bed technique and release in vitro was selected as the evaluate index. The formulation was optimized by full design test based on the studies of coating factors. RESULTS: The optimal coating formulation was shown at the ratio of Eudragit RS 30D and Eudragit RL 30D to 5:1, the loading weight of polymers of 45%, the plasticizer concentration of 20% and 35% talcum powder. CONCLUSION: The perfect sustained release of tetrandrine pellets can be obtained by adjusting the ratio of Eudragit RS 30D and Eudragit RL 30D and the loading weight of polymers.

Self-Nanoemulsifying Drug Delivery System of Tetrandrine for Improved Bioavailability: Physicochemical Characterization and Pharmacokinetic Study.

The main purpose of this study was to investigate the potential of self-nanoemulsified drug delivery system (SNEDDS) to improve the oral bioavailability of tetrandrine (Tet). SNEDDS was developed by using rational blends of excipients with good solubilizing ability for Tet which was selected based on solubility studies. Further ternary phase diagram was constructed to determine the self-emulsifying region. The optimal formulation with the best self-nanoemulsified and solubilization ability consisted of 40% (w/w) oleic acid as oil, 15% (w/w) SPC and 30% (w/w) Cremophor RH-40 as surfactant, and 15% (w/w) PEG400 as cosurfactant. The average droplet size and zeta-potential of the optimal Tet SNEDDS were 19.75±0.37 nm and 1.87±0.26 mv, respectively. The dissolute rate of Tet SNEDDS in various dissolution media was remarkably faster than Tet commercial tablet. Moreover, in vivo pharmacokinetic study results show that significant increase (p≤ 0.05) in the peak concentration (Cmax) and the area under the curve (AUC) of Tet was observed after the oral administration of Tet SNEDDS and the absorption of Tet from SNEDDS resulted in approximately 2.33-fold increase in oral bioavailability compared with the commercial tablet. Our research suggests that the prepared Tet SNEDDS could be a good candidate for improved the dissolution and oral bioavailability of Tet.

[Study on preparation technology of plumula nelumbinis Alkaloid Dripping Pill and determination of content by HPLC].

OBJECTIVE: To determine the optimum technical parameters through controlling the different factors and the content of Dripping Pill. METHOD: Time of dissolution, spherical degree and pill weight as parameters, the influential factors were investigated by orthogonal test and then to determine the content of liensinine, isoliensinine, neferine in plumula nelumbinis Alkaloid Dripping Pill. RESULT: The optimum condition: 75% PEG4000 as matrix, methyl-silicon oil as refrigerant, 4 cm dripping distance, 10 degrees C refrigerant, 30 drippings per minute. CONCLUSION: The good quality pills can be produced through this process and the HPLC determination method is simple, reliable and can be used in the quality control of plumula nelumbinis Alkaloid Dripping Pill.

Targeting vincristine plus tetrandrine liposomes modified with DSPE-PEG2000-transferrin in treatment of brain glioma.

Glioma is the most frequent primary tumor, and the treatment efficiency is unsatisfactory for the obstacle of the blood brain barrier (BBB), the multidrug resistance (MDR) and the properties of cancer cell invasion and vasculogenic mimicry (VM) formation. In this study, a kind of TF modified vincristine plus tetrandrine liposomes was developed to overcome those limitations. In vitro results showed that TF modified vincristine plus tetrandrine liposomes with suitable physicochemical property could enhance the transport across the BBB, increase the cellular uptake, inhibit the MDR, and block the cancer cell invasion and VM channels. In vivo results demonstrated that TF modified vincristine plus tetrandrine liposomes could significantly prolong the circulation time, obviously accumulate in brain tumor location, thus leading to a robust anticancer efficacy in glioma-bearing mice. These data suggest that TF modified vincristine plus tetrandrine liposomes offer a promising strategy for treating brain glioma.

Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells.

One of the promising strategies to overcome tumor multidrug resistance (MDR) is to deliver anticancer drug along with P-glycoprotein (P-gp) inhibitor simultaneously. To enhance the cancer cellular internalization and implement the controlled drug release, herein an iRGD peptide-modified lipid-polymer hybrid nanosystem (LPN) was fabricated to coload paclitaxel (PTX) and tetrandrine (TET) at a precise combination ratio. In this co-delivery system, PTX was covalently conjugated to poly (D,L-lactide-co-glycolide) polymeric core by redox-sensitive disulfide bond, while TET was physically capsulated spontaneously for the aim to suppress P-gp in advance by the earlier released TET in cancer cells. As a result, the PTX+TET/iRGD LPNs with a core-shell structure possessed high drug loading efficiency, stability and redox-sensitive drug release profiles. Owing to the enhanced cellular uptake and P-gp suppression mediated by TET, significantly more PTX accumulated in A2780/PTX cells treated with PTX+TET/iRGD LPNs than either free drugs or non-iRGD modified LPNs. As expected, PTX+TET/iRGD LPNs presented the highest cytotoxicity against A2780/PTX cells and effectively promoted ROS production, enhanced apoptosis and cell cycle arrests particularly. Taken together, the co-delivery system demonstrated great promise as potential treatment for MDR-related tumors based on the synergistic effects of P-gp inhibition, enhanced endocytosis and intracellular sequentially drug release.

Defense-related Proteins from Chelidonium majus L. as Important Components of its Latex.

The aim of this review is to cover most recent research on plant pathogenesis- and defenserelated proteins from latex-bearing medicinal plant Chelidonium majus (Papaveraceae) in the context of its importance for latex activity, function, pharmacological activities, and antiviral medicinal use. These results are compared with other latex-bearing plant species and recent research on proteins and chemical compounds contained in their latex. This is the first review, which clearly summarizes pathogenesisrelated (PR) protein families in latex-bearing plants pointing into their possible functions. The possible antiviral function of the latex by naming the abundant proteins present therein is also emphasized. Finally latex-borne defense system is hypothesized to constitute a novel type of preformed immediate defense response against viral, but also non-viral pathogens, and herbivores.

Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile.

The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.

Characterization of the Uptake Efficiency and Cytotoxicity of Tetrandrine-Loaded Poly(N-vinylpyrrolidone)-Block-Poly(ε-caprolactone) (PVP-b-PCL) Nanoparticles in the A549 Lung Adenocarcinoma Cell Line.

Tetrandrine (Tet) has been previously reported to induce apoptosis in several cancer cell lines. However, poor Tet solubility has limited its further application. The lipophilicity of Tet suggests that the development of Tet-loaded biodegradable polymeric micelle delivery systems may be possible. In our previous work, we demonstrated the superior antitumor efficiency of Tet-loaded mPEG-PCL nanoparticles (NPs) in colorectal cancer cell lines. In the present study, we report that a spherical core­shell Tet-loaded nanoparticle structure was prepared using a nanoprecipitation method by employing amphiphilic poly(N-vinylpyrrolidone)-block-poly(ε-caprolactone) (PVP-b-PCL) copolymers as drug carriers. Tet was incorporated into the NPs with high encapsulation efficiency and released in a sustained release pattern. Moreover, coumarin-6 (hydrophobic fluorescence)-loaded Tet-NP uptake was shown to be mediated mainly by endocytosis from the NPs and was more efficient than that of rhodamine B (hydrophilic fluorescence)-loaded NP uptake, which was mainly dependent upon infiltration. The endocytic uptake process was blocked by NaN3, a mitochondrial inhibitor. In vitro studies using the A549 cell line demonstrated the superior cytotoxicity and apoptosis induction ability of Tet-NPs in dose- and time-dependent manners compared to free Tet. The data obtained from this study, therefore, not only confirm the potential use of Tet to treat lung cancer but also suggest an effective manner by which to improve the anticancer efficiency of Tet in nano-drug delivery systems.

Noscapine comes of age.

Noscapine is a phthalideisoquinoline alkaloid, which represents a class of plant specialized metabolites within the large and structurally diverse group of benzylisoquinoline alkaloids. Along with the narcotic analgesic morphine, noscapine is a major alkaloid in the latex of opium poppy (Papaver somniferum) that has long been used as a cough suppressant and has undergone extensive investigation as a potential anticancer drug. Cultivated opium poppy plants remain the only commercial source of noscapine. Despite its isolation from opium more than two centuries ago, the almost complete biosynthesis of noscapine has only recently been established based on an impressive combination of molecular genetics, functional genomics, and metabolic biochemistry. In this review, we provide a historical account of noscapine from its discovery through to initial investigations of its formation in opium poppy. We also describe recent breakthroughs that have led to an elucidation of the noscapine biosynthetic pathway, and we discuss the pharmacological properties that have prompted intensive evaluation of the potential pharmaceutical applications of noscapine and several semi-synthetic derivatives. Finally, we speculate on the future potential for the production of noscapine using metabolic engineering and synthetic biology in plants and microbes.

Improved delivery of the natural anticancer drug tetrandrine.

The study aims at designing a nanoparticle-based delivery system to improve the efficacy of the natural compound tetrandrine against lung cancer. Nanoparticles from poly(lactic-co-glycolic acid) (PLGA) were prepared by the emulsion solvent diffusion method and characterized for their physicochemical properties and drug-loading efficiency. Furthermore, the cellular uptake and the anti-cancerous activity was studied on A549 cell line. To investigate the surface properties and uptake, three different stabilizers were used to analyze the effect on size and zeta potential of nanoparticles as well as the effect on the cellular uptake. Nanoparticles in the size range of 180-200 nm with spherical shape were obtained with polyvinyl alcohol (PVA), Pluronic-F127 (PF127) and didodecyldimethylammonium bromide (DMAB), 2%, 1% and 0.1%, respectively. An entrapment efficiency of 50-60% with a loading of 1.5-2% was observed. In vitro release profile at pH 7.4 PBS solution showed a consistent release over 168 h. All particle systems showed an improved performance over the pure drug at the same drug concentration. DMAB stabilized particles demonstrated the most pronounced effect against A549 cells compared to pure drug while PVA stabilized particles were least effective in terms of antitumor activity.