Sustained-release Preparation Research Articles

Sustained-release preparation for the treatment of distal renal tubular acidosis

Sustained-release preparation for the treatment of distal renal tubular acidosis

Electrospinning synthesis of nanofiber membrane with biodegradable as sustained-release formulation of fenofibrate

Fenofibrate is widely used as a lipid-lowering drug. However, fenofibrate has a short half-life, so it needs to be prepared as a sustained-release preparation to prolong the administration time. In this study, fenofibrate nanofibers are prepared by electrospinning using the biodegradable material polylactic acid as a drug carrier. To improve the hydrophilicity and cumulative drug release rate, polyvinylpyrrolidone is introduced to prepare a composite drug-loaded nanofibrous membrane. The experimental results show that the hydrophilicity and cumulative release rate are improved. This study provides a simple and efficient method for the preparation of fenofibrate nanofibrous membranes with sustained-release effects.

Temperature-responsive microcapsule hydrogel fabricated by pickering emulsion polymerization for pheromones application

Insect pheromone is a natural effective biological pesticide. To improve the utilization efficiency of pheromone pesticides and reduce labor costs, a sustained and controlled release preparation coordinating with the circadian rhythm of insects has been proposed by our previous report. However, that preparation has some deficiencies, such as the loading capacity of pheromone and sustained time. In order to overcome the existent shortcomings, a temperature-responsive release microcapsule hydrogel loaded with myrcene (as a pheromone model) was fabricated by Pickering emulsion polymerization using modified SiO2 nanoparticles as a stabilizer of microcapsule wall, octadecane and Poly(N-isopropylacrylamide) (PNIPAM) separately as temperature responders of microcapsule core and wall in the present study. The morphological structure and thermal performance of the microcapsule hydrogel were characterized. The release behaviors of myrcene at different environmental temperatures and alternating temperature cycles were also tested. The results indicated that myrcene was successfully loaded in the Myrcene/Octadecane@SiO2-PNIPAM (MOSP) microcapsule hydrogel with encapsulation efficiency and loading capacity of 80.3 % and 13.3 %, respectively. The results of the myrcene release under simulated diurnal temperature cycles revealed that the cumulative release amount was only about 43 % during 15 cycles and release rates respectively were about 0.79 μg/h at 35 °C and 0.058 μg/h at 25 °C, which demonstrated the persistent temperature sensitivity and good temperature rhythm remained after 15 cycles. These results suggested that the MOSP microcapsule hydrogel had a good controlled release effect on myrcene and could adapt well to the circadian rhythm activity of some insects. Therefore, this study provided a promising strategy to improve the utilization efficiency of pheromones through the combination of octadecane and PNIPAM as pheromones release controllers.

Use of strongly acting sustained-release opioids in pediatrics : Pitfalls and solutions for morphine and hydromorphone

In pediatrics, adequate treatment with potent opioids requires the administration of sustained-release preparations for many patients; however, the dosing and administration of sustained-release morphine and hydromorphone preparations via gastrointestinal tubes confronts providers with amajor hurdle, especially as the company Mundipharma GmbH has discontinued the production and distribution of the preparation MST retard granules in 2019, which has been proven for these purposes in pediatrics. The aim of this study was to establish aproduction technique for available sustained-release opioid preparations, which are particularly suitable for use in the low-dose range required in pediatrics and which can also be administered via gastrointestinal tubes. Low-dose preparations were produced by opening of morphine and hydromorphone capsules and weighing of the sustained-release pellets. To evaluate the partition, an analysis of the drug content via high performance liquid chromatography (HPLC) was conducted. Moreover, the administration via gastrointestinal tubes (charrière, Ch 8-Ch10) was examined by an ex vivo experiment. The examination showed apracticable method to produce low dosages of sustained-release morphine and hydromorphone. The preparations are in accordance with the test for content uniformity of the European Pharmacopoeia (Ph. Eur.). Furthermore, the pellets were administered to gastrointestinal tubes Ch8 (morphine) and Ch10 (hydromorphone) by asyringe application technique and passed the tubes completely. The production technique can be considered as safe and enables the off-label oral application or application via gastrointestinal tubes of sustained-release opioids in pediatrics.

Pharmacokinetics and Drug-Drug Interaction of Allisartan Isoproxil and Indapamide Sustained-Release Formulation.

Allisartan isoproxil (AI) is an angiotensin II type 1 receptor blocker and be converted into the active substance EXP3174 in vivo. We evaluated the drug-drug interactions of AI and an indapamide sustained-release (Ind SR) preparation, as well as the pharmacokinetic characteristics and safety of AI and Ind SR in healthy subjects. The trial was set up in 6 sequences and 3 cycles, and each cycle contained a 7-day washout period. Subjects received 3 different trial drugs (A, AI; B, Ind SR; C, AI+Ind SR) during 3 different cycles. Twenty-four subjects were enrolled in the clinical trial. Of these, 22 completed the study, 2 subjects dropped out due to adverse events (AEs). For subjects given AI alone or combined with Ind SR, the pharmacogenetic parameters Cmax and the geometric mean ratio of steady state (combined/single) of EXP3174 was 130%. The geometric mean ratio of area under the concentration-time curve over the dosing interval at steady state (combined/single use) was 144.5%. Therefore, the combination of Ind SR had an impact on the pharmacokinetics of AI. Then, the results indicated that the AI combination had no effect on the pharmacokinetics of Ind SR. Serious AEs did not occur. The AEs in this clinical trial were the same as those for AI and Ind SR. Combined administration resulted in 2 cases (2 subjects) of Grade 3 hypotension and 1 case of Grade 3 hypotension with AI alone. Considering that this trial included healthy volunteers, the risk of hypotension was expected to be manageable.

Nanoparticle-releasing xerogel films prepared by a one-step method

Aggregation remains a challenge in the development of solid dosage forms of nanoparticles. Herein, we investigated whether xerogel films can allow sustained release of nanoparticles encapsulating curcumin (as a model drug) while preventing their aggregation. Such films can be fabricated by casting nano-oil droplets in an aqueous solution. In this study, curcumin and poly (lactic-co-glycolic acid) (PLGA) were dissolved in methylene chloride and emulsified in a polyvinyl alcohol (PVA)-propylene glycol (PG) solution. While drying the cast, the nano-oil droplets solidified to form nanoparticles. Concurrently, the PVA-PG solution was gelatinated and further dried to form a xerogel. The xerogel film containing curcumin-loaded nanoparticles disintegrated in vitro within 10 min, releasing the nanoparticles without aggregation. The emitted nanoparticles in turn released curcumin at a first-order rate over 90 min. Thus, xerogel films containing nanoparticles could be useful sustained-release solid preparations for delivering nanoparticles at a controlled rate without aggregation.

Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial

BackgroundUnderstanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients.MethodsRadioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 μg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 − 24 were calculated at the last visit.ResultsSerum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 − 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group.ConclusionCombined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested.IRCT registration numberIRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13. Registration date: 08/12/2021.

Polyvinyl alcohol composite hydrogels/epoxidized natural rubber composites (CMCS/PVA/CS-ENR) with core-shell structure as biomass coating material for slow-release nitrogen fertilizer

Using natural rubber (NR)/chitosan (CS)/polyvinyl alcohol (PVA) as raw materials, biodegradable semi-IPN (semi-interpenetrating polymer network) composites were prepared by thiol-epoxy click reaction under UV light, which was used as the shell of sustained release preparation. Using polyvinyl alcohol (PVA)/carboxymethyl chitosan (CMCS) as raw material and vanillin as the cross-linking agent, hydrogen-bonded hybrid network hydrogel loaded with urea was prepared by freeze-thaw cycle, which was used as the core of sustained-release preparation. Finally, a green-coated urea fertilizer with core-shell structure was prepared to ameliorate the environmental pollution of slow-release fertilizer (for example, synthetic polymer-coated fertilizers are difficult to biodegrade), as well as to achieve the water retention and the effective slow-release. The high CS/PVA contents and the combination of the hydrogel core and the rubber shell significantly improved the mechanical properties of the coating material (tensile strength above 5 MPa, elongation at break up to 1400 %), hydrophilicity (to promote the degradation rate of the rubber shell) and soil water retention of the coating material (close to pure hydrogel), showing enhanced reaction. In terms of slow-release effect, coated nitrogen fertilizer with 3 % CS content, 5 % PVA content and 10-min coating time (SRP3/10) achieved the best slow-release effect of nitrogen (N) in water (62.7 % at 10 days), which was related to the hydrophilicity, semi-IPN skeleton and the cross-linking structure of the network, and the release conformed to the Korsmeyer-Peppas model with a non-Fickian diffusion release mechanism, indicating that the behavior of N release was mediated by a combination of drug diffusion and skeleton dissolution.

Preparation, Properties and Therapeutic Effect of a TPL Nanoparticle Thermosensitive Gel for Intra-Articular Injection.

Most injectable preparations for the articular cavity are solution-type preparations that are frequently administered because of rapid elimination. In this study, triptolide (TPL), an effective ingredient in the treatment of rheumatoid arthritis (RA), was prepared in the form of a nanoparticle thermosensitive gel (TPL-NS-Gel). The particle size distribution and gel structure were investigated by TEM, laser particle size analysis and laser capture microdissection. The effect of the nanoparticle carrier material PLGA on the phase transition temperature was investigated by 1H variable temperature NMR and DSC. The tissue distribution, pharmacokinetic behavior, four inflammatory factors and therapeutic effect were determined in a rat RA model. The results suggested that PLGA increased the gel phase transition temperature. The drug concentration of the TPL-NS-Gel group in joint tissues was higher than that in other tissues at different time points, and the retention time was longer than that of the TPL-NS group. After 24 days of administration, TPL-NS-Gel significantly improved the joint swelling and stiffness of the rat models, and the improvement degree was better than that of the TPL-NS group. TPL-NS-Gel significantly decreased the levels of hs-CRP, IL-1, IL-6 and TNF-α in serum and joint fluid. There was a significant difference between the TPL-NS-Gel and TPL-NS groups on Day 24 (p < 0.05). Pathological section results showed that inflammatory cell infiltration was lower in the TPL-NS-Gel group, and no other obvious histological changes were observed. Upon articular injection, the TPL-NS-Gel prolonged drug release, reduced the drug concentration outside the articular tissue and improved the therapeutic effect in a rat RA model. The TPL-NS-Gel can be used as a new type of sustained-release preparation for articular injection.

Transdermal administration of ibuprofen-loaded hexagonal liquid crystal gel for enhancement of drug concentration in the uterus: in vitro and in vivo evaluation

Primary dysmenorrhea is a common disease in women, and oral administration of Ibuprofen (IBU) is associated with first-pass effects and gastrointestinal irritation. Here, we developed ibuprofen-loaded hexagonal liquid crystal (IBU HLC) gel for transdermal administration. In this study, the structure of prepared IBU HLC was characterized using polarizing microscopey (PLM) and small angle X ray diffraction (SAXS). In vitro drug release behavior and percutaneous penetration were investigated, and drug transdermal behavior was observed by confocal laser scanning microscope (CLSM). Finally, the pharmacokinetic profile and tissue distribution were investigated after transdermal administration. The PLM and SAXS results showed that the inner structure of IBU HLC was hexagonal phase. Moreover, in vitro release, skin permeation and CLSM demonstrated that IBU HLC had an excellent sustained-release effect, and a good transdermal penetration effect accompanied by the combination of multiple percutaneous routes. Pharmacokinetic studies indicated that IBU entered the blood circulation through abdominal transdermal administration in small amounts, mainly entering the uterus, and had a certain targeting ability. In conclusion, the IBU HLC gel would be a promising sustained-release preparation for transdermal administration to relieve dysmenorrhea with a significant drug concentration in the uterus.

Quality by design driven development and evaluation of thermosensitive hydrogel loaded with IgY and LL37-SLNs to combat experimental periodontitis

Egg yolk immunoglobulin (IgY) and LL37, potent antibacterial substances, can fight against periodontitis. This work aimed to develop a locally injectable hydrogel for potential co-delivery of special IgY and LL37-loaded solid lipid nanoparticles (LL37-SLNs) to synergistically inhibit the proliferation of oral pathogens, thus relieving periodontal inflammation and redness. The formulation of thermosensitive hydrogel loaded with IgY and LL37-SLNs was developed by adopting the Quality by Design approach. Then the formulations were optimized by two-factor three-level full factorial design by Design-Expert software. Finally, the optimized formulation was characterized and estimated in vitro and in vivo. In vitro release and antibacterial activity studies have revealed that the optimized formulation was homogeneous and can be released slowly, with sustainably antibacterial power. And the physical and chemical composition analysis and morphological observations further confirmed the sustained-release capability. On the other hand, in vivo studies proved that the optimized formulation significantly decreased gingival redness, bleeding, and plaque formation, avoided excessive resorption of alveolar bone, and reduced the levels of inflammatory factor in periodontitis rats. In conclusion, the optimized thermosensitive hydrogel loaded with IgY and LL37-SLNs may be a promising local sustained-release preparation for the effective treatment of periodontal diseases.

Chronic Administration of Melatonin: Physiological and Clinical Considerations

Exogenous melatonin is commonly used to treat insomnia, other sleep problems, and numerous medical illnesses, including Alzheimer's disease, autism spectrum disorder, and mild cognitive impairment in adults and children. There is evolving information regarding issues with the use of chronic melatonin. The present investigation was a narrative review. Melatonin usage has risen dramatically in recent years. Many countries only allow melatonin prescriptions. In the United States (U.S.), it is classified as a dietary supplement accessible over the counter and can be derived from animals, microorganisms, or, most commonly, made synthetically. No regulatory agency oversees its manufacturing or sale in the U.S. melatonin concentration of marketed preparations varies widely between product labels and manufacturers. Melatonin's ability to induce sleep is detectable. However, it is modest for most people. Sleep length appears to be less important in sustained-release preparations. The optimal dosage is unknown, and routinely used amounts vary substantially. Melatonin's short-term negative effects are minimal, resolve at medicine cessation, and do not usually prevent usage overall. Much research on long-term melatonin administration has found no difference between exogenous melatonin and placebo in terms of long-term negative effects. Melatonin at low to moderate dosages (approximately 5-6 mg daily or less) appears safe. Long-term usage appears to benefit certain patient populations, such as those with autism spectrum disorder. Studies investigating potential benefits in reducing cognitive decline and increased longevity are ongoing. However, it is widely agreed that the long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation.

内視鏡的除去が有効であった鉄徐放錠過量内服の1例(Effectiveness of endoscopy in managing sustained iron release preparation overdose)

要旨 鉄剤は鉄欠乏貧血などでしばしば処方されるが，自傷目的に過量内服されることがある。服薬量が少なくても重篤化する場合があり症例の蓄積が必要である。今回，硫化鉄徐放錠を過量服薬したが内視鏡的除去により重症化を防ぎえたと考えられる症例を経験したので報告する。症例は20歳代の女性。近医で処方されていた硫化鉄徐放錠22錠（鉄2,310mg）を一気に服用した。約4時間後に嘔気と上腹部痛を呈し救急車で来院した。鉄摂取量は50mg/kgで，搬入時の血清鉄濃度（以下，SIC）は386µg/dLと軽度高値を示した。救急外来で撮像した腹部単純レントゲン写真で胃内に多数の錠剤を認めたため，内視鏡的除去後にキレート剤を投与した。SICは経時的に低下し第2病日退院した。鉄中毒では最大SICや鉄摂取量が中毒症状に関連するとされ，服薬後4～6時間程度の最大SICを確認する必要がある。SICの測定が不可能な状況では，鉄摂取量や，意識，循環，消化器症状などの臨床症状，胃内の薬剤残存状況などから重症度を判断する。鉄の排泄経路は限られており，重篤となる可能性がある場合には積極的に消化管除染やキレートを行う必要がある。徐放性鉄剤は服薬後6～12時間で最大SICに達する。本症例は内服から5時間後の腹部単純レントゲン写真で未吸収の薬剤が胃内に残存しており，内視鏡的除去を行うことで以後の血中濃度上昇を抑え，重症化を防いだと考える。

CLINICAL PREVALENCE AND CURRENT TREATMENT STANDARDS FOR GERD AND DYSPEPSIA, AND PERCEPTION OF EFFECTIVENESS AND SAFETY OF ITOPRIDE IN INDIAN PATIENTS - A PHYSICIANS' SURVEY

In India, little information is available regarding physicians’ use of various treatment options in the management ofGastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). This survey aimed to understand theprevalence of GERD and FD across age and gender, and the treatment options used in the management of FD and GERDin the Indian clinical setting. A physician-based research survey was conducted between August 2020 and January2021using a 22-item questionnaire. A total of 379 physicians spread over 159 cities in India participated in the survey.Nearly 70% of physicians encountered 20%-40% of patients with symptoms of GERD and dyspepsia every month, with10-20% being newly diagnosed. Moreover, FD was reported in 10%-30% of patients by 70% of physicians; further,20%-40% of them had 30% patients with overlapping GERD+FD. For patients with FD, 56% of respondents reportedan overlap between epigastric pain syndrome (EPS) and post-prandial syndrome (PDS). Most patients were aged 30-55years. The most preferred choice for treatment of EPS was proton pump inhibitors (PPIs) followed by prokinetics otherthan itopride, and itopride. The use of prokinetics for EPS was quite low and for PDS, PPIs were prescribed by almost50% of the physicians. Pantoprazole was the most preferred PPI. Itopride was considered for all patient profiles, withmost respondents using the sustained-release preparation. Findings from this research survey will help guide physicianson the actual prevalence of and optimal management strategies for GERD and FD in India.

Effervescent Tablets: Everything You Need To Know

Oral dosage forms are the most popular way of taking medication, despite having some disadvantages compared with other methods like risk of slow absorption of the medicament, which can be overcome by administering the drug in liquid form, therefore, possibly allowing the use of a lower dosage. However, instability of many drugs in liquid dosage form limits its use. Effervescent technique can be used as alternate to develop a dosage form which can accelerate drug disintegration and dissolution, is usually applied in quick release preparations. Along with the development of new pharmaceutical technique, effervescent tablets are more and more extensively to adjust the behavior of drug release, such as in sustained and controlled release preparations, pulsatile drug delivery systems, and so on. In this review we have discussed about formulation, evaluation, advantages of effervescent tablets and also demonstrated the new applying of effervescent technique in effervescent tablets. Keywords: Effervescent tablets. Carbon tablet, Effervescent granules.

Preparation and Characterization of Gastroreten-tive Sustained Release In-situ Gel of Lafutidine

Background: The in-situ solutions, which float in the gastrointestinal region after gelation, is suited for long-term drug release. In this study, natural and synthetic polymers were used to try to build a Gastro-Retentive controlled release in-situ gel. To modulate the rate of drug distribution and increase bioavailability and stability, gastro-retentive controlled release in-situ gels were prepared. &#x0D; Materials and Methods: For this project, 32 factorial designs were chosen. The two independent variables were sodium alginate (X1) and the ratio of HPMC K100M: Gellan Gum (X2) was preserved at the same concentration. As the study mentioned, sodium alginate is a natural polymer that is employed to build the gel matrix, while HPMC K100M and gellan gum serve as release retardants. &#x0D; Results and Discussion: The drug and excipients study performed by FTIR and DSC revealed that both the drug and polymers used were compatible with other. Out of all the batches prepared LG7 proved to be the optimized batch because of the acceptable pH with a floating time of more than 24 hours and maximum drug content of 99.92 ± 0.04% and the lag time of 71 ± 0.57seconds. The viscosity of the optimized batch was found to be dependent on the concentration of sodium alginate and the viscosity before gelling and after gelling was found to be 32719 ± 1.65 and 39851 ± 1.77 cps. The mucoadhesion strength of the prepared optimized formulation was found to be 5.621 ± 0.41N/cm2. The optimized LG7 batch showed the most sustained rate of drug release with having a matrix model as the best-fitted model. The histopathology study revealed that the formulation was safe to use without causing any degeneration of the tissues. The stability study showed that the prepared formulation was stable for the time of the study as no significant changes were observed. Lastly, the sustained behavior of the prepared in-situ gel was due to the calcium carbonate in the gelling formulation which released carbon dioxide into the gastrointestinal environment, and the formulation became porous and buoyant, extending the residence period and the floating of the gel was due to the pH-induced ion gelation process that caused the gel to float.&#x0D; Conclusion: It was concluded that the prepared controlled release in-situ gel of Lafutidine may prove to be a potential candidate for safe and effective controlled drug delivery for an extended period.

Preparation of pelargonic acid vesicles and sustained drug release

This study has selected the medium-chain saturated fatty acid pelargonic acid as the raw material for the first time, and added the surface catalyst Tween 80 to the aqueous solution to form pelargonic acid–Tween 80 composite vesicles by a surface tension method. The compound vesicle was used to encapsulate five heterocyclic drugs (cefazolin sodium, chlorpromazine hydrochloride, gemcitabine hydrochloride, metronidazole, and isoniazid), all of which have disadvantages when used directly, and the effects of the vesicles on the five kinds of drugs were evaluated in terms of encapsulation rate and the in vitro sustained release in a simulated artificial intestinal fluid environment. The results revealed that the pelargonic acid–Tween 80 composite vesicles exhibit an encapsulation efficiency above 45%, and that the encapsulated drugs achieve a cumulative release effect of 6–10 h in a simulated artificial intestinal fluid environment, and the cumulative release rate is above 35%. This study proves that pelargonic acid–Tween 80 composite vesicles can be used as a carrier for encapsulated drugs, and this can extend the time of action of the drugs. This research illustrates the potential for application of pelargonic acid in the field of medicine.

HPLC-MS/MS analysis of primary alkaloids in rat plasma after oral administration of “Nux vomica - Glycyrrhiza glabra decoction”: A pharmacokinetic study

Ethnopharmacological relevanceDecoction is the most common form of administering traditional Chinese medicine (TCM). During the preparation of decoction, the high temperature and complex chemical environment result in the formation of complex and multiple phases. The differences in drug components in different phases induce gastrointestinal absorption and physiological response. Nux vomica (Strychnos nux-vomica L) is a typical toxic TCM used in China, with remarkable pharmacological activity. In order to reduce its toxicity, nux vomica (NV) is often decocted with Glycyrrhiza glabra (GG) in clinic, and the detoxification mechanism has always been the focus of research interest. Most studies investigated the compatibility of NV-GG, but the in vivo behavior of individual constituents based on phase state has yet to be elucidated. Aim of the studyTo investigate the pharmacokinetic behavior of typical toxic components in different phase states of “NV-GG decoction” in rat plasma. Materials and methodsThe sediment, suspension, colloid and true solution of “NV-GG decoction” was obtained via physical methods. The main components in different phase states were analyzed via reliable UFLC-Q-TOF-MS high-resolution mass spectrometry. A rapid and accurate HPLC-qqq-MS/MS method was established and validated for accurate determination of brucine and strychnine levels in plasma, followed by pharmacokinetic evaluation of different phase states of “NV-GG decoction” in rats. Kinetex F5 100A (50 mm × 3.0 mm, 2.6 μm) column was used for chromatographic separation. Aqueous solution containing acetonitrile and 0.1% formic acid was used as the mobile phase, followed by gradient elution at 0.4 mL/min. Mass spectra were detected by electrospray ionization (ESI) multiple reaction monitoring (MRM) in positive ion mode. ResultsFifteen different alkaloids were detected in different phase states of “NV-GG decoction”. Strychnine and brucine, which are toxic components with high content, were selected for quantitative analysis. The established UPLC-qqq-MS/MS method is accurate and reliable with a good linearity (R2 > 0.99) in the respective concentration range, satisfying the quantitative requirements. The pharmacokinetic parameters of different phase states of rats differed significantly after gavage. The deposition phase was the most prominent. The index components showed higher Cmax, AUC0 and Tmax, while the T1/2, MRT, V/F and CL/F were the smallest, with a relatively slow plasma clearance rate in rats. The true solution group showed the lowest Tmax and the fastest absorption. ConclusionThis method has been successfully utilized to study the pharmacokinetics of different phase states of “NV-GG decoction”. Among the four phases, the deposition phase contributed to a large proportion of the in vivo kinetic behavior similar to that of sustained-release preparations, with slow absorption of toxic components and prolonged peak time. The pharmacokinetic parameters and plasma concentration-time curves of each phase can be used to study toxicity reduction of NV-GG and increase its biocompatibility.

Preparation, Characterization, and In Vitro Release of Curcumin-Loaded IRMOF-10 Nanoparticles and Investigation of Their Pro-Apoptotic Effects on Human Hepatoma HepG2 Cells

Curcumin (CUR) has a bright future in the treatment of cancer as a natural active ingredient with great potential. However, curcumin has a low solubility, which limits its clinical application. In this study, IRMOF-10 was created by the direct addition of triethylamine, CUR was loaded into IRMOF-10 using the solvent adsorption method, and the two were characterized using a scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG) methods, and Brunauer–Emmett–Teller (BET) analysis. We also used the MTT method, 4′,6-diamidino-2-phenylindole (DAPI) staining, the annexin V/PI method, cellular uptake, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) to perform a safety analysis and anticancer activity study of IRMOF-10 and CUR@IRMOF-10 on HepG2 cells. Our results showed that CUR@IRMOF-10 had a CUR load of 63.96%, with an obvious slow-release phenomenon. The CUR levels released under different conditions at 60 h were 33.58% (pH 7.4) and 31.86% (pH 5.5). Cell experiments proved that IRMOF-10 was biologically safe and could promote curcumin entering the nucleus, causing a series of reactions, such as an increase in reactive oxygen species and a decrease in the mitochondrial membrane potential, thereby leading to cell apoptosis. In summary, IRMOF-10 is an excellent drug carrier and CUR@IRMOF-10 is an effective anti-liver cancer sustained-release preparation.

Stability of Citral Sustained-release Preparation and Its Inhibitory Effect on Aspergillus flavus

Stability of Citral Sustained-release Preparation and Its Inhibitory Effect on Aspergillus flavus