Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

Combustion Characteristics of Solid Sustained-Release Energetic Materials

A solid sustained-release energetic material sample,an eruption device and a complete test system were prepared further to analyse the combustion characteristics of solid sustainedrelease energetic materials.The high-temperature heat flux generated by the combustion of the samples from the eruption device was used to penetrate the Q235 target plate.In addition,the meaning and calculation formula of energy density characterising the all-around performance of heat flux were proposed.The numerical simulation of the combustion effect of samples was carried out.According to the data comparison,the numerical simulation results agreed with the experimental results,and the maximum deviation between the two was less than 8.9%.In addition,the structure of the combustion wave and high-temperature jet was proposed and analysed.Based on theoretical analysis,experimental research and numerical simulation,the theoretical burning rate formula of the sample was established.The maximum error between the theoretically calculated mass burning rate and the experimental results was less than 9.8%.Therefore,using the gas-phase steady-state combustion model to study the combustion characteristics of solid sustained-release energetic materials was reasonable.The theoretical burning rate formula also had high accuracy.Therefore,the model could provide scientific and academic guidance for the theoretical research,system design and practical application of solid sustained-release energetic materials in related fields.

Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

Effects of Sustained-Release Calcium Hydroxide and Sustained-Release Hydrochloric Acid on Nutrient Di-gestion and Absorption of Rabbits

Rabbits with the body weight of （2.0 ± 0.5 ） kg were chosen, to study the effects of sustained-release calcium hydroxide and sustained-release hydro- chloric acid on nutrient digestion and absorption of rabbits. The results showed that sustained-release calcium hydroxide promoted digestion and absorption of nutri- ents, especially calcium and crude protein. The digestibility of calcium and crude protein was increased from 89.8% and 93.8% to 41.0% and 65.2%, respec- tively. Sustained-release hydrochloric acid was adverse to digestion and absorption of nutrients, especially calcium and crude protein. The digestibility of calcium and crude protein were decreased from 55.5% and 84.9% to 28.4% and 68.7%, respectively. The promotion effects of sustained-release hydrochloride on diges- tion lasted for 3 -4 d. Therefore, sustained-release calcium hydroxide promoted digestion and absorption of calcium and protein, while digestion and absorption of fat remained at a high level no matter what the condition was. Consequently, increasing the intake of fat would cause over nutrition. However, taking sustained-re- lease hydrochloric acid would reduce nutrient digestion and absorption.

Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion

Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.

Release performance and sustained-release efficacy of emamectin benzoate-loaded polylactic acid microspheres

High-performance liquid chromatography （HPLC） was employed to determine drug release rates based on emamectin benzoate concentrations in the medium. Release kinetics equations were used to fit the drug release behavior. The effects of particle size and release medium pH on the release rate were also investigated. The indoor toxicity of emamectin benzoate-loaded polylactic acid microspheres on the diamondback moth larva （Plutella xylostella） was studied to explore drug sustained-release performance. In acidic and neutral media, the drug release behavior of the microspheres was in accord with the first-order kinetics equation. Increasing the spray dosage of emamectin benzoate-loaded polylactic acid microspheres initially resulted in an equivalent insecticidal efficacy with the conventional emamectin benzoate microemulsion. However, the drug persistence period was four-fold longer than that observed using the conventional formulation. The developed emamectin benzoate-loaded polylactic acid microspheres showed dramatic sustained-release performance. A treatment threshold of greater than 35 mg mL-1 was established for an efficient accumulated release concentration of emamectin benzoate-loaded microspheres.

Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques

The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.

The preparation and the in-vitro pharmacodynamics study of the intracapsular sustained-release preparations for the prevention of posterior capsule opacification

Docetaxel-loaded sustained-release preparation based on 2-Hydroxyethyl methacrylate(HEMA)and Methyl methacrylate(MMA)cross-linked copolymer(P(HEMA-co-MMA))was prepared to examine the potential use for preventing posterior capsule opacification(PCO).The preparations were prepared by polymerizing the mixture of HEMA,MMA,cross-linking agent(EGDMA),initiator(AIBN)and docetaxel.The influence factors and mechanism of drug release were studied in the experiments.FT-IR,X-RD and SEM methods were used to characterize the polymer(P(HEMA-co-MMA))and docetaxel-loaded sustained-release preparations.Biocompatibility of P(HEMA-co-MMA)and in-vitro effect of docetaxel-loaded sustained-release preparations were also evaluated.The results showed that docetaxel could release sustainedly from these preparations prepared by cross-linking polymerization.And the release rate could be accelerated by increasing the MMA ratio or EGDMA ratio of the polymer.Release mechanism of docetaxel fitted the Higuchi model well.The results of IR and X-RD showed that only a hydrogen bond was formed between docetaxel and P(HEMA-co-MMA).Docetaxel dispersed in P(HEMA-co-MMA)in amorphous form.The elution test showed that P(HEMA-co-MMA)had good biocompatibility and the in-vitro pharmacodynamics study proved that docetaxel could release stably from the preparations and inhibit HLECs’proliferation.The docetaxel-loaded sustained-release preparations proved to be a promising therapy for preventing PCO.These results also lay a theoretical and experimental foundation for the future.

Tunable and sustained-release characteristics of venlafaxine hydrochloride from chitosan–carbomer matrix tablets based on in situ formed polyelectrolyte complex film coating

The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride(VH) as a drug model, the feasibility of using chitosan(CS), carbomer(CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS–CBM matrix tablets were investigated. It was found that CS–CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR), in situ self-assembled polyelectrolyte complex(PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation(IVIVC) established successfully. In conclusion, CS–CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.

No long-term survival benefit with sustained-release 5-fluorouracil implants in patients with stages Ⅱ and Ⅲ gastric cancer

BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer is still unelucidated.AIM To explore the long-term survival benefit of using sustained-release 5-FU implants in stage Ⅱ and stage Ⅲ gastric cancer patients.METHODS Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release(SR) chemotherapy with 5-FU was used or not(NSR). The primary end-point was 5-year overall survival. Kaplan–Meier method with logrank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients.RESULTS In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219(70.9%) were men, with an average age of 58.25 years. Furthermore, 56(18.1%) received neoadjuvant chemotherapy, and 191(61.8%) were in TNM stage Ⅲ. In addition, 158 patients received intraoperative sustainedrelease chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate(P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival.CONCLUSION Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Evaluation of Control Effects against Sugarcane Pests：A New Sustained-release and Long-lasting Pesticide and Convenient and Efficient Pesticide Application Technology

[Objective]The paper was to screen a new ideal sustained-release,long-lasting and low-toxic pesticide and convenient and efficient pesticide application technology for controlling Ceratovacuna lanigera and Baliathrips serratus. [Method]2% Imidacloprid GR were selected and applied in the soil for field efficacy trial. [Result] The optimum dosage of 2% imidacloprid GR was 30 kg/hm^2（ active ingredient 600 g）,which can be mixed with fertilizer（ 30 kg pesticide and 40-80 kg fertilizer per hm^2） once combined with sugarcane planting management or big ridging during February and June. The control effects against C. lanigera and B. serratus could be more than 98. 2% and 81. 1%,respectively. The actual yield and sugar content in various pesticide treatments were increased by 33 390 kg/hm^2 and 6. 6% respectively compared to blank control. [Conclusion]2% imidacloprid GR has good control effects on C. lanigera and B. serratus. It is a new pesticide with ideal sustained-release,long-lasting and low-toxin effects against C. lanigera and B. serratus. Therefore,it could be used alternatively with other pesticides,to delay production and development of drug resistance.

In vitro release of 1,3-bis(2-chloroethyl)-1-nitrosourea sustained-release microspheres and the distribution in rat brain tissues

BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity. OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue. DESIGN: A repetitive measurement. SETTING:Central Pharmacy, General Hospital of Chinese People’s Armed Police Forces. MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.; BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet). High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm, 4.6 mm×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL. METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively at 4 hours, 1, 2, 3, 7 and 15 days, the residual MS was removed from the brain tissue. The rest amount of BCNU was determined with HLPC, and the curve of BCNU-PLA-MS release was drawn as compared with the amount of BCNU in the implanted tablets. Besides, brain tissues (1 g) at the implanted side and the contralateral one were obtained respectively, blood sample (0.5 mL) was also collected, 3H-BCNU was counted radioactively in radioactive liquid flash solution. The distributions of BCNU-PLA-MS in normal rat brain tissue and serum were detected. The analysis of variance was applied to compare the intergroup differences of the measurement data. MAIN OUTCOME MEASURES: ① Characteristics of BCNU-PLA-MS release in phosphate buffered solution (PBS) and rat brain tissue; ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum. RESULTS: ① Release of BCNU-PLA-MS in PBS and rat brain tissue: The BCNU released from BCNU-PLA-MS could be sustained for over 2 weeks both in PBS and brain tissue. In PBS, the released rate of BCNU was over 15% at 24 hours, nearly 50% at 72 hours and over 90% at 15 days. In brain tissue, the released rate was 8% at 4 hours, 16% at 24 hours, 60% at 72 hours, respectively, and BCNU could be sustained released for over 15 days. ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum: The concentrations of BCNU in the ipsilateral brain tissue were 6 to 70 times higher than those in the contralateral one. The concentrations of BCNU in the ipsilateral brain tissue were obviously higher than those in serum and contralateral brain tissue (F =103.47, P < 0.01). CONCLUSION: BCNU-PLA-MS can increase the drug concentration in targeted brain tissue, decrease that in the non-targeted brain tissue, reduce general toxic and side effects, and have good releasing function.

Toxic response of aquatic organisms to guide application of artemisinin sustained-release granule algaecide

In our previous study,we prepared the granules by embedding artemisinin into alginate-chitosan using microcapsule technology.These granules can release artemisinin sustainably and have a strong inhibitory effect on the growth of both single Microcystis aeruginosa and mixed algae.To safely and effectively use artemisinin sustained-release granules to control algal blooms,the ecotoxicity was studied by assessing their acute and chronic toxicity to Daphnia magna(D.magna)and Danio rerio(D.rerio),along with their antioxidant activities.The results showed that the 48-h median effective concentration(EC50)of pure artemisinin to D.magna was 24.54 mg/L and the 96-h median lethal concentration(LC50)of pure artemisinin to D.rerio was 68.08 mg/L.Both values were classified as intermediate toxicity according to the Organization for Economic Co-operation and Development(OECD).The optimal algae inhibitory concentration of artemisinin sustained-release granules(1 g/L)had low acute toxicity to both D.magna and D.rerio.The sustained-release granules had higher chronic toxicity to D.magna than to D.rerio.Partial indices of D.magna were inhibited by granules when the concentrations were larger than 0.1 g/L.Low granule concentration had an inductive effect on antioxidant enzyme activities in D.magna and D.rerio.With the increase of the exposure concentration and time,the enzyme activity presented a trend of first increasing and then decreasing,and the overall changes were significant.The change trend and range of enzyme activity indicated that the granules could cause serious oxidative stress to D.magna and D.rerio,and the changes were consistent with the results of toxicity experimentation.

Preparation and evaluation of sustained-release azithromycin tablets in vitro and in vivo

The objective of this study was to prepare azithromycin(AZI)sustained-release products in order to allow for a high dose to be administered,reduce gastrointestinal side-effects and increase the compliance of patients.AZI sustained-release tablets with different release performance(F-I:T_(100%)=3 h and F-II:T_(100%)=8 h in pH 6.0 phosphate buffer)were successfully prepared by wet granulation.The in vitro release rate and drug release mechanism were studied.The release rate of F-Iwas affected by dissolutionmedia with different pH,but not for F-II.HixsoneCrowellmodel was the best regression fitting model for F-I and F-II.Additionally,F-I and F-II both belonged to non-Fick diffusion.Oral pharmacokinetics of the two tablets and one AZI dispersible tablet as reference were studied in six healthy beagle dogs after oral administration.Compared with the reference,the C_(max) of F-I and F-II were decreased,and the T_(max) were prolonged,in that case which meet the requirement of sustained-release tablets.The relative bioavailability of F-I and F-II were 79.12%and 64.09%.T-test ofAUC_(0-144),and AUC_(0-∞) for F-I and F-II indicated there was no significant difference between F-I and F-II.These mean that the extended release rate did not induce different pharmacokinetics in vivo.

PDLLA/β-TCP/HA/CHS/NGF Sustained-release Conduits for Peripheral Nerve Regeneration

Using nerve guide conduits (NGCs) to promote the regeneration of PNI is a feasible alternative to autograft.Compared with NGCs made of single material,composite NGCs have a greater development prospect.Our previous research has confirmed that poly(D,L-lactic acid)/β-tricalcium phosphate/hyaluronic acid/chitosan/nerve growth factor (PDLLA/β-TCP/HA/CHS/NGF) NGCs have excellent physical and chemical properties,which can slowly release NGF and support cell adhesion and proliferation.In this study,PDLLA/β-TCP/HA/CHS/NGF NGCs were prepared and used to bridge a 10 mm sciatic nerve defect in 200-250 g Sprague-Dawley (SD) rat to verify the performance of the NGCs in vivo.Substantial improvements in nerve regeneration were observed after using the PDLLA/β-TCP/HA/CHS/NGF NGCs based on gross post-operation observation,triceps wet weight analysis and nerve histological assessment.In vivo studies illustrate that the PDLLA/β-TCP/HA/CHS/NGF sustained-release NGCs can effectively promote peripheral nerve regeneration,and the effect is similar to that of autograft.

Clinical observation of Baitou Weng Decoction combined with mesalazine sustained-release tablets in treating heat-toxic and smoldering ulcerative colitis

Objective:To observe the clinical efficacy of Baitou Weng Decoction combined with mesalazine sustained-release tablets in the treatment of ulcerative colitis with febrile heat and its effect on immune function and serum inflammatory factors.Methods: A total of 84 patients with ulcerative colitis were randomly divided into control group and treatment group, with 42 cases in each group. The control group was given mesalazine sustained-release tablets orally, while the treatment group was given Baitou Weng Decoction and mesalazine sustained-release tablets orally. The treatment period was 30 days and the patients were followed up for 3 months. After treatment, the clinical efficacy, quality of life, immune function and serum inflammatory factors of the two groups were observed.Results: The effective rate of treatment group (90.47%) was higher than that of control group (73.81%) (P<0.05);compared with before treatment, the scores of inflammatory bowel disease quality of life questionnaire scale in both groups were significantly improved (P<0.05), and the difference between the two groups was significant (P<0.05);after treatment, the plasma CD4+/CD8+ ratio and NK+ levels in both groups were significantly higher than those before treatment (P<0.05), and the treatment group was changed. The serum levels of tumor necrosis factor-α, interleukin-17 and interleukin-23 were significantly decreased in both groups after treatment (P<0.05), and the improvement was more significant in the treatment group (P<0.05). No significant adverse reactions were observed in the treatment group.Conclusions: Modified Baitou Weng Decoction combined with mesalazine in the treatment of heat-toxic and incandescent ulcerative colitis can significantly improve the clinical efficacy, improve the quality of life of patients, effectively regulate the expression level of serum inflammatory factors in ulcerative colitis patients, promote the recovery of patients' immune function, and have high drug safety.

Boosted sustained-release with iron-based MOF-derived mesoporouscarbon-spheres as a nitroimidazole drugs carrier

Metal-organic framework(MoF)with a buildable internal structure has aroused great interest focus as self-sacrificing precursors of porous carbon(PC).However,as a drug carrier,the MOF-derived PC developed thus far are generally composed of irregular powder shape due to their crystalline nature,which consequently causing the cerebral infarction,cerebral thrombosis,and other blood diseases.In this article,we propose a novel approach to constructing amorphous carbon microspheres(AcMs)by dis-torting the topological network through hydrothermal treatment precursors of MIL-101(Fe).Then,a distinctive MIL-101(Fe)-derived spherical porous carbons(MSPC)is achieved through high temperature calcination toward ACMs.Effects of the glucose initial concentration and hydrothermal treatment time on the sphericity of the as-prepared mesoporous MsPC were investigated in depth.And the loading capacities and sustained-release performances of nitroimidazole drugs over MsPC through simulation internal environment of human body at different pH values was systematically evaluated.The nitro-imidazole drugs loading rate and release time of MsPC are 10% and 17 h under preferred process.Furthermore,the MSPC exhibited very low toxicity on Hela cells and 293T cells at the concentrations tested(10-800μg mL^(-1)).This study,therefore,supports the potential of the mesoporous carbon spheres as a carrierfor nitroimidazole drug delivery.

Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,patients are reluctant to take medication day after day to manage incurable occasional gout flares,and suffer from possible long-term toxicity.Therefore,a safe and easy-tooperate drug delivery system with simple preparation for the long-term management of gout is very necessary.Here,a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal.This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention.Furthermore,its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models.Besides,the drug co-delivery system could help avoid long-term daily oral colchicine,a drug with a narrow therapeutic index.This system also avoids mass injection of uricase by improving its stability,enhancing the clinical application value of uricase.In general,this two-drug system reduces the dosage of uricase and colchicine and improves the patient’s compliance,which has a strong clinical translation.

Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

Growth hormone deficiency(GHD)has become a serious healthcare burden,and presents a huge impact on the physical and mental health of patients.Here,we developed an actively separated microneedle patch(PAA/NaHCO_(3)^(-)Silk MN)based on silk protein for sustained release of recombinant human growth hormone(rhGH).Silk protein,as a friendly carrier material for proteins,could be constructed in mild full-water conditions and ensure the activity of rhGH.After manually pressing PAA/NaHCO_(3)^(-)Silk MN patch to skin for 1 min,active separation is achieved by absorbing the interstitial fluid(ISF)to trigger HCO_(3)^(-)in the active backing layer to produce carbon dioxide gas(CO_(2)).In rats,the MN patch could maintain the sustained release of rhGH for more than 7 days,and produce similar effects as daily subcutaneous(S.C.)injections of rhGH in promoting height and weight with well tolerated.Moreover,the PAA/NaHCO_(3)^(-)Silk MN patch with the potential of painless self-administration,does not require cold chain transportation and storage possess great economic benefits.Overall,the PAA/NaHCO_(3)^(-)Silk MN patch can significantly improve patient compliance and increase the availability of drugs,meet current unmet clinical needs,improve clinical treatment effects of GHD patients.