[Preparation and effect against cervical cancer invasion in vitro of harmine-loaded photosensitive liposomes].

Despite the development of HPV vaccines and screening programs, cervical cancer is still a serious threat to women's health. Early-stage cervical cancer is mainly treated by surgery. However, considering the serious complications after surgery, hyperthermia is recommended to enhance the effect of chemotherapy, retain the integrity of cervix, improve the treatment effect, which provides a therapeutic basis for the early treatment of cervical cancer. The photosensitive liposomes containing harmine and dye IR-780 were prepared by thin-film dispersion method and separated by Sephadex G-50 dextran gel column. The preparation conditions were optimized as the mass ratio of phospholipid to cholesterol membrane material being 8∶1 and that of drug to lipid being 1∶20. The results of HPLC showed that the encapsulation efficiency of harmine was 55.6%±0.18%. The prepared photosensitive liposomes were round and evenly distributed under transmission electron microscope, with the particle size of(125.2±0.62) nm determined by Marvin particle size analyzer and the Zeta potential of(-2.55±0.76) mV. Additionally, the photosensitive liposomes had the photothermal conversion efficiency, an important property of photothermal agent, of 27.1%±0.86%. The photosensitive liposomes stored at 4 ℃ showed stable encapsulation efficiency in the first 14 days without flocculation. The sulforhodamine B(SRB) assay was employed to determine the inhibitory effect of the liposomes on the proliferation of HeLa cells under near-infrared(NIR) irradiation or not, which showcased stronger inhibitory effect under NIR irradiation. The results of Transwell assay indicated that the prepared liposomes significantly inhibited the invasion and migration of HeLa cells in vitro. The findings of this study provide a basis for the treatment of cervical cancer with harmine.

Development, Optimization, and Evaluation In Vitro/In Vivo of Oral Liquid System for Synchronized Sustained Release of Levodopa/Benserazide.

To enhance efficiency, convenience, and safety of Parkinson's disease (PD) treatment for geriatric patients, an advanced suspension of Levodopa/Benserazide hydrochloride (LD/BH) has been prepared by cation-exchange resin and used to synchronize sustained release of LD and BH by optimizing coating parameters and prescription. For the purpose, LD and BH were immobilized on the surface of cation-exchange resin, respectively. Based on HPLC results, the cation-exchange resin showed high loading capacity. The studies on drug loading mechanism indicated that both drugs were immobilized by electrostatic interaction rather than physical adsorption. After PEG modification, pretreated drug-resin complexes were coated by emulsion-solvent evaporation method. In order to control drug release in a sustained manner, coating parameters of drug-resin microcapsules were optimized respectively by single-factor analysis. Further, coating prescription of the microcapsules was optimized to synchronize sustained release of LD and BH in vitro by orthogonal design. Utilizing optimal LD-resin microcapsules and BH-resin microcapsules, LD/BH suspension, containing both of them, was prepared by an optimal formulation and characterized by accelerated test and pharmacokinetic study in vivo. The accelerated test confirmed high stability of LD/BH suspension. According to pharmacokinetic results in vivo, in contrast with LD/BH commercial tablets, LD/BH suspensions did not only synchronize sustained release of both drugs but also show good bioequivalence. As LD/BH sustained release suspension can synchronize sustained release of multiple active ingredients by oral administration, the suspension presents promising oral dosage forms for geriatric patients with PD. An advanced Levodopa/Benserazide hydrochloride (LD/BH) suspension, prepared by cation-exchange resin and optimized microencapsulation, synchronizes sustained releases of LD and BH in vivo to benefit Parkinson's disease treatment for geriatric patients.

[Optimize preparation of compound licorice microemulsion with D-optimal design].

In order to increase the solubility of essential oil in compound licorice microemulsion and improve the efficacy of the decoction for treating chronic eczema, this experiment intends to prepare the decoction into microemulsion. The essential oil was used as the oil phase of the microemulsion and the extract was used as the water phase. Then the microemulsion area and maximum ratio of water capacity was obtained by plotting pseudo-ternary phase diagram, to determine the appropriate types of surfactant and cosurfactant, and Km value-the mass ratio between surfactant and cosurfactant. With particle size and skin retention of active ingredients as the index, microemulsion prescription was optimized by D-optimal design method, to investigate the in vitro release behavior of the optimized prescription. The results showed that the microemulsion was optimal with tween-80 as the surfactant and anhydrous ethanol as the cosurfactant. When the Km value was 1, the area of the microemulsion region was largest while when the concentration of extract was 0.5 g·mL⁻¹, it had lowest effect on the particle size distribution of microemulsion. The final optimized formulation was as follows: 9.4% tween-80, 9.4% anhydrous ethanol, 1.0% peppermint oil and 80.2% 0.5 g·mL⁻¹ extract. The microemulsion prepared under these conditions had a small viscosity, good stability and high skin retention of drug; in vitro release experiment showed that microemulsion had a sustained-release effect on glycyrrhizic acid and liquiritin, basically achieving the expected purpose of the project.

[Share experiment: hospital mobile pharmaceutical teams, a proven concept!]. / Partage d'expérience : les équipes pharmaceutiques mobiles à l'hôpital, un concept qui fait ses preuves !

A few months ago, the pharmacy department of the University Hospital of Poitiers was located in the basement of the hospital; communicating with care units by fax, phone or messenger. Today, drugs and medical devices, are stored in a 3400m(2) logistic platform and most of the delivery activity is robotized. Control and validation of prescriptions and dispensing activities are done by the pharmaceutical teams directly in the care units. Quality indicators allow us to improve our services regularly. A great success and interesting prospects for clinical pharmacy.

Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms.

The emergence of antibiotic resistance poses a global health threat. High-risk patients such as those with neutropenia are particularly vulnerable to opportunistic infections, sepsis, and multidrug-resistant infections, and clinical outcomes remain the primary concern. Antimicrobial stewardship (AMS) programs should mainly focus on optimizing antibiotic use, decreasing adverse effects, and improving patient outcomes. There is a limited number of published studies assessing the impact of AMS programs on patients with neutropenia, where early appropriate antibiotic choice can be the difference between life and death. This narrative review updates the current advances in strategies of AMS for bacterial infections among high-risk patients with neutropenia. Diagnosis, drug, dose, duration, and de-escalation (5D) are the core variables among AMS strategies. Altered volumes of distribution can make standard dose regimens inadequate, and developing skills towards a personalized approach represents a major advance in therapy. Intensivists should partner antibiotic stewardship programs to improve patient care. Assembling multidisciplinary teams with trained and dedicated professionals for AMS is a priority.

Regional Antimicrobial Stewardship Program in a Provincial Medical Zone in Japan: a Multifaceted Approach.

Antimicrobial resistance (AMR) is a threat to patient health. However, data to optimize antimicrobial use are limited. Furthermore, reducing antibiotic use raises concerns regarding patient safety. The effectiveness of antibiotics in reducing the prevalence of AMR is controversial. Researchers at the Japanese Red Cross Ishinomaki Hospital (JRCIH), the only tertiary care hospital in the medical zone, along with local medical and pharmacy associations and public health centers have been leading the AMR control program since 2018. The program involves lectures aimed at optimizing antimicrobial use, regular publication of surveillance data of drug-resistant strains at the JRCIH, and presentation of first-line treatments for community-acquired infections. The delivery of oral antimicrobial agents across the region in 2020 was 28.7% lower than that in 2013, with delivery of cephalosporins, quinolones, and macrolides decreasing by 34.8%, 46.8%, and 56.0%, respectively. Despite these reductions, there has been no associated increase in the number of patients with severe infectious diseases admitted to the JRCIH. The rates of representative drug-resistant bacterial strains, such as extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus, decreased by half. Herein, we demonstrated the potential of collaborative efforts to optimize antimicrobial agent use and reduce the AMR prevalence without compromising patient safety.

Preparation and Evaluation of Compound Nanxing Pain Relief Gel / 世界科学技术-中医药现代化

Objective To prepare Compound Nanxing Pain Relief Gel(CNPRG)and evaluate its quality and sensitization.Methods CNPRG uses Carbopol 980 NF as the matrix;Appearance,viscosity,coating,centrifugal stability,cold stability,thermal stability as comprehensive indicators,single test and Box-Behnken effector method to optimize the prescription;The quality evaluation methods of appearance,pH,viscosity,stability,vapor phase identification of volatile components,and determination of diaconitine and eugenol content of CNPRG were preliminarily established;CNPRG sensitization was assessed by Active Cutaneous Anaphylaxis.Results The best prescription for CNPRG was Carbopol 980 NF 0.35 g,drug 1.02 g,glycerol 5.00 g,and pH 6.20.CNPRG ′s appearance likes jelly,is smooth,uniform and delicate;pH=6.20±0.03;viscosity 68.43±1.14 Pa·s;Centrifugation,high,low temperature stability,no stratification and precipitation;Identify camphor,(±)-Borneol and(±)-Isoborneol,Cinnamaldehyde,eugenol,phenol;Hypaconitine content 0.2983±0.0073 μg·g-1;Eugenol content 155.66±0.97 μg·g-1;CNPRG confirmed no sensitization.Conclusion CNPRG has good appearance,stable quality and no sensitization,and it can provide a choice for the development of new dosage forms of compound Nanxing pain relief cream to alleviate sensitization.

A fast, sensitive, and high throughput method for the determination of esomeprazole in dog plasma by UHPLC-MS/MS: Application to formulation development of the compound preparation of esomeprazole.

To investigate deeply into the preclinical pharmacokinetics and prescription design of esomeprazole, a sensitive, high throughput and robust UHPLC-MS/MS method had been developed and fully validated for the analysis of esomeprazole in dog plasma. Esomeprazole and diazepam (IS) were fast extracted from plasma by alkalified organic solvent, and separated on MP-C18 column with methanol and 0.1% formic acid. The quantification of esomeprazole and IS had been achieved using fragmentation transitions of m/z 346.1→198.1 and m/z 285.0→193.2 in MRM detection under positive ESI mode. The concentration of esomeprazole in dog plasma was linear with the range of 3.75-500ng/mL. The precisions of intra- and inter-day were no more than 11.6%, while the accuracies were all within ±9.7% of the nominal values. The recovery was no more than 77.06%, and the matrix effect, stability, dilution integrity tests were all satisfied the currently criterion. Then the method was successfully performed to evaluating pharmacokinetics of esomeprazole and optimizing the prescription of modified esomeprazole with varied addition of sodium bicarbonate. Consequently, a pharmacokinetic study of three doses esomeprazole with the optimized addition of sodium bicarbonate in dogs has been successfully researched for the first time. It could be a promising approach to improve the stabilization of acid-labile esomeprazole and would provide a useful reference for the formulation design of esomeprazole.

Capsaicin-loaded nanolipoidal carriers for topical application: design, characterization, and in vitro/in vivo evaluation.

Capsaicin has been used in clinical applications for the treatment of pain disorders and inflammatory diseases. Given the strong pungency and high oil/water partition coefficient of capsaicin, capsaicin-loaded nanolipoidal carriers (NLCs) were designed to increase permeation and achieve the analgesic, anti-inflammatory effect with lower skin irritation. Capsaicin-loaded NLCs were prepared and later optimized by the Box-Behnken design. The physicochemical characterizations, morphology, and encapsulation of the capsaicin-loaded NLCs were subsequently confirmed. Capsaicin-loaded NLCs and capsaicin-loaded NLCs gel exhibited sustained release and no cytotoxicity properties. Also, they could significantly enhance the penetration amount, permeation flux, and skin retention amounts of capsaicin due to the application of NLCs. To study the topical permeation mechanism of capsaicin, 3,3'-dioctadecyloxacarbocyanine perchlorate (Dio) was used as a fluorescent dye. Dio-loaded NLCs and Dio-loaded NLCs gel could effectively deliver Dio up to a skin depth of 260 and 210 µm, respectively, primarily through the appendage route on the basis of version skin sections compared with Dio solution, which only delivered Dio up to 150 µm. In vivo therapeutic experiments demonstrated that capsaicin-loaded NLCs and capsaicin-loaded NLCs gel could improve the pain threshold in a dose-dependent manner and inhibit inflammation, primarily by reducing the prostaglandin E2 levels in the tissue compared with capsaicin cream and capsaicin solution. Meanwhile, skin irritation was reduced, indicating that application of NLCs could decrease the irritation caused by capsaicin. Overall, NLCs may be a potential carrier for topical delivery of capsaicin for useful pain and inflammation therapy.

Optimization of pH response and mitochondrial targeting bifunctional hyperoside liposomes by central composite design response surface methodology and its in vitro evaluation / 中草药

Objective: To optimize preparation of mitochondrial targeting hyperoside liposomes (DLD/Hyp-Lip), and study its stability in fetal bovine serum, in vitro release behavior and mitochondrial targeting. Methods: DLD/Hyp-lip was prepared by film dispersion method. Single factor experiment was carried out with entrapment efficiency and drug loading as indexes to investigate the effects of the ratio of phospholipids to hyperoside (Hyp) and DSPE-PEG (distearoyl phosphoethanolamine-polyethylene glycol) to DLD on DLD/Hyp-Lip. The formulation of DLD/Hyp-Lip was further optimized by central composite design response surface methodology. The appearance, size and potential of liposomes were observed by transmission electron microscope and particle size analyzer. The stability and drug release rate of liposomes in fetal bovine serum were evaluated by serum stability test and in vitro drug release test. The drug delivery system was evaluated by mitochondrial targeting. Results: The optimal formula of DLD/ Hyp-Lip was as follows: the ratio of total phospholipids to hyperoside was 12.50:1, the ratio of total phospholipids to cholesterol was 6.00:1, and the dosage ratio of DSPE-PEG to DLD was 3:5, the encapsulation efficiency was (95.57 ± 0.56) %, the drug loading was (8.55 ± 0.57) %. The prepared liposomes had good appearance, the particle size of the lip was (124.9 ± 3.4) nm, and the potential was (-6.2 ± 1.9) mV. It was stable in fetal bovine serum and accumulated in vitro release medium for 24 h. Mitochondrial targeting experiments showed that DLD/Hyp-Lip could promote the accumulation of drugs in the mitochondria. Conclusion: This method is simple and convenient, and can accurately and effectively optimize the preparation process of DLD/Hyp-Lip. The prepared DLD/Hyp-Lip has high encapsulation efficiency, small particle size, uniform distribution and good sustained-release effect, which lays the foundation for further in vivo research of DLD/Hyp-Lip. DLD/Hyp-Lip with hyperoside has good mitochondrial targeting of liver cancer cells and is a potentially efficient mitochondrial targeted drug delivery system for liver cancer cells.

Use of the American Experiences for Reference on the Intervention of Pharmacists to Prescribing Behavior in China / 中国药学杂志

OBJECTIVE: To strengthen pharmacist intervention in prescribing behavior of doctors, so as to further standardize prescribing behavior.METHODS: Through the review of the advantages and disadvantages of the relevant laws, education training and assessment system for prescription intervention in the USA, a deep analysis was made in combination with the Chinese system and the characteristics of the medical staff.RESULTS: A new clinical pathway was introduced to standardize the intervention of doctors′ prescriptions, so as to improve the level of diagnosis and treatment and the environment for medical treatment in China.CONCLUSION: Improving pharmacists′ professional accomplishment and introducing Internet model and intelligent medical technology can improve the linkage among clinical, community medical institutions and social pharmacies, and also enhance the feasibility and reliability of Internet prescription drug purchase intervention. Promote the closed-loop connection and continuous upgrading of the pharmaceutical industry chain, gradually realize the standardization model of diagnosis and treatment, and then promote the results of the overall medical level.

Preparation and evaluation of the formulation of budesonide rectal in situ thermogel / 中国药科大学学报

@#To prepare a budesonide rectal thermogel. The gel solution was prepared by cold method, and the gelation temperature of the gel solution was determined by reverse tube method. The amount of poloxamer 407(P407), poloxamer 188(P188)and hydroxy propyl methyl cellulose(HPMC)was optimized by central composite design/response surface method. The in vivo gelation character was investigated after rectal administration of the budesonide thermogel into the rat, and the in vitro drug release from the gel was examined by the Franz diffusion cell method. Finally, the optimal formulation includes 0. 002% budesonide, 0. 93% HPMC, 2. 00% P188, and 18. 31% P407. It is preferable to obtain the appropriate formulation for budesonide rectal in situ thermogel, which can achieve wide distribution and adhesion to the rectum, as well as long-term drug release.

Optimization of prescriptions for Yuanhu Zhitong Orally Disintegrating Tablets based on central composite design-response surface methodology / 中草药

Objective To optimize the best prescription of Yuanhu Zhitong Oral Disintegrating Tablets (YZODT). Methods Using the single factor test, the prescription of the tablets was optimized by central composite design-response surface methodology (CCD-RSM) with the tablet wetting time and the disintegration time limit as evaluation index, so as to determine the best preparation process. Results The dosages of the optimized prescription of MCC, L-HPC, and PVPP were 30%, 15%, and 5%, respectively. The average disintegration time of the optimized YZODT was 42.89 s, and the deviation from the predicted value was 3.27%. Conclusion The optimized YZODT has the advantages of fast disintegration, moderate hardness, convenient use, and simple process.

Optimize preparation of compound licorice microemulsion with D-optimal design / 中国中药杂志

In order to increase the solubility of essential oil in compound licorice microemulsion and improve the efficacy of the decoction for treating chronic eczema, this experiment intends to prepare the decoction into microemulsion. The essential oil was used as the oil phase of the microemulsion and the extract was used as the water phase. Then the microemulsion area and maximum ratio of water capacity was obtained by plotting pseudo-ternary phase diagram, to determine the appropriate types of surfactant and cosurfactant, and Km value-the mass ratio between surfactant and cosurfactant. With particle size and skin retention of active ingredients as the index, microemulsion prescription was optimized by D-optimal design method, to investigate the release behavior of the optimized prescription. The results showed that the microemulsion was optimal with tween-80 as the surfactant and anhydrous ethanol as the cosurfactant. When the Km value was 1, the area of the microemulsion region was largest while when the concentration of extract was 0.5 g·mL⁻¹, it had lowest effect on the particle size distribution of microemulsion. The final optimized formulation was as follows: 9.4% tween-80, 9.4% anhydrous ethanol, 1.0% peppermint oil and 80.2% 0.5 g·mL⁻¹ extract. The microemulsion prepared under these conditions had a small viscosity, good stability and high skin retention of drug; in vitro release experiment showed that microemulsion had a sustained-release effect on glycyrrhizic acid and liquiritin, basically achieving the expected purpose of the project.

Effect of the Optimal Prescription of Huiru Yizeng on Hyperprolactinemia and Hyperplasia of Mammary Glands in Model Rats / 医药导报

Objective To investigate the effect of the optimal prescription of huiru yizeng on rats with hyperplasia of mammary gland and hyperprolactinemia. Methods Fifty-six female Wistar rats were randomly divided into 7 groups (n=8), including normal control group, model control group, sodium chloride group, bromocriptin group, rupi sanjie group, the original prescription group and optimizing prescription group. Rat model of mammary gland hyperplasia with hyperprolactinemia was replicated in 6 groups but not the normal control group. The successfully established experimental rats were given corresponding drugs by intragastric gavage. After 30 days, the levels of the estradiol, progesterone, and prolactin were detected, and the pathomrphology of glandular tissue was observed. Results Prolactin levels of model control group, the original prescription group and optimize prescription group were (69.47 ±6.08), (53.13 ±10.59), and (28.41 ±6.37) pg·mL-1, respectively . Compared with that in the model control group, the contents of prolactin in both the optimal prescription group and the original prescription group were reduced, but the optimal prescription group was better (P<0. 01). In the original prescription group, the lobules of mammary gland showed a few of hyperplasia, the individual alveoli and duct showed a slight hyperplasia, and a small amount of secretions was found in the duct. The degree of the hyperplasia was alleviated in the optimal prescription group similar to that observed in the normal control group, which showed that there was no hyperplasia in the lobules of mammary gland or no secretions in the duct. Conclusion The therapeutic effects of the optimal prescription are much better than the original prescription, which can effectively lower the level of prolactin, adjust the balance among the prolactin , estrogen and progesterone, and alleviate the pathological hyperplasia of mammary glands in the model rats.

Research on Preparation Technology of Xiaoer Qingfei Dispersible Tablets / 中国中医药信息杂志

Objective To optimize the prescription of preparation technology of Xiaoer Qingfei Dispersible Tablets. Methods The filler, disintegrant, adhesive, lubricant, and drug loading were screened by single factor tests. The combined application proportion of three disintegrating agents, PVPP, CMS-Na, and L-HPC, were optimized by orthogonal test. Results The best prescription of preparation technology of dispersible tablets:microcrystalline cellulose as filler;silica gel powder as lubricant;75%alcohol as the adhesive;PVPP, L-HPC, and CMS-Na as combined disintegrants (L-HPC∶PVPP∶CMS-Na=4∶3∶6). The disintegration time of prepared dispersible tablets was less than 3 minutes, and all through the No.2 sieve. Dispersible uniformity was in accordance with the provisions. Conclusion Xiaoer Qingfei Dispersible Tablets prepared by the optimized preparation process are stable and feasible, and suitable for clinical application.

Application of central composite design in optimization of the formulation of aspirin ointment / 中国药学杂志

OBJECTIVE: To optimize the formulation of aspirin ointment. METHODS: With cumulative permeation quantity within 6 h and shin irritation as indexes, the method of central composite design was used to optimize the formulation of aspirin ointment, taking the most important three ingredients including sodium lauryl sulfale(X1), sodium citrate (X2) and triethanolamine (X3) as the study subjects. RESULTS: The optimized formulation of aspirin ointment was composed of 1.41% sodium lauryl sulfate, 3.5% sodium citrate and 3.0% triethanolamine. Three batches of aspirin ointment were prepared using the optimized formulation, for which the average cumulative permeation quantity within 6 h was 990.18 μg · cm-2, and no obvious shin irritation was observed. CONCLUSION: Central composite design is successfully used lo optimize the formulation of aspirin ointment.