Optimal Release Rate Research Articles

Unraveling the Therapeutic Prospects of Solid Lipid Nanoparticles for the Treatment of Parasitic Diseases

Parasites induce a spectrum of illnesses, ranging from mild to severe, often causing significant global outbreaks. Existing antiparasitic drugs exhibit toxicity and notable side effects. Nanocarriers offer a promising solution by mitigating these issues through reduced side effects, enhanced target delivery, and additionally regulated prolonged active ingredient release. Solid lipid nanoparticles (SLNs), a subset of lipid nanoparticles (LNPs), have gained prominence for their favorable attributes. SLNs present themselves as a feasible option among colloidal carriers, offering an optimal release rate, stability, and precise target delivery. Their potential to deliver natural antiparasitic products is particularly noteworthy. Recent advancements in utilizing nanoparticles to enhance SLN stability and loading capacity are also explored in this review. The narrative encompasses SLN development, preparation methods, characterization, and the incorporation of drugs for combating parasitic diseases, offering insights into the evolving landscape of antiprotozoal SLN-saturated medications

Formation by high power ultrasound of mimicking human fat emulsions stabilized with milk fat globule membrane

Ultrasound (US) is an innovative food processing technique that has gained significant interest for its role in modifying proteins. Our study focused on how different US time exposure influence the stability, interfacial structure, and rheological characteristics of whey protein infused with milk fat globule membrane (MFGM). Results indicated that a 9-min ultrasound treatment (US-9) of protein, yielding an emulsion with particle size of 338.3 nm and ζ-potential of −48 mV, was optimal for enhancing functional properties of the emulsion. The US-9 emulsion exhibited different surface rheological properties compared to other emulsions, revealing a heterogeneous MFGM stabilization interface predominantly made of MFGM fragments, free phospholipids, and proteins. The US-9 emulsion surface covered more phospholipids, indicating improved emulsion persistence, based on interfacial protein and phospholipid content calculations and microstructure observation. While the US-9 emulsion did not affect fat digestion, the US-6 min treatment resulted in an optimal fatty acid release rate. Further experimentation may be necessary to elucidate the intricate relationship between ultrasound duration and fat digestion. These findings have leaded to a better understanding of the emulsification capabilities of MFGM materials, as well as a foundation to improve infant formula quality.

Optimized carbonization of coffee shell via response surface methodology: A circular economy approach for environmental remediation

The disposal of coffee shell waste on farmland, is a common practice that can causing the environmental and waste valuable resources. Carbonization has been identified as an effective method for transforming coffee shells into useful products that mitigate environmental pollution. Through the response surface methodology, the carbonization conditions of the coffee shells were optimized and its potential as a biochar-based slow-release urea fertilizer was explored. Experiments were conducted on coffee shell performance under varying carbonization conditions such as temperature (600–1000 °C), time (1–5 h), and heating rate (5–20 °C/min). The results indicated that the ideal urea adsorption was 56.3 mg/g, achieved under carbonization conditions of 2.83 h, 809 °C, and 15.3 °C/min. The optimal nutrient release rate within seven days was 45.4% under carbonization conditions of 3.19 h, 813 °C, and 15.0 °C/min. The infrared spectroscopy analysis indicates that carbonization conditions influenced the absorption peak intensity of coffee shell biochar, while the functional group types remain unchanged. The biochar exhibits diverse functional groups and abundant pores, making it a promising candidate for use as a biochar-based fertilizer material. Overall, the findings demonstrate an effective waste management approach that significantly reduces environmental pollutants while remediating pollution.

Lenacapavir: A Novel, Potent, and Selective First-in-Class Inhibitor of HIV-1 Capsid Function Exhibits Optimal Pharmacokinetic Properties for a Long-Acting Injectable Antiretroviral Agent.

Lenacapavir (LEN) is a picomolar first-in-class capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) with a multistage mechanism of action and no known cross resistance to other existing antiretroviral (ARV) drug classes. LEN exhibits a low aqueous solubility and exceptionally low systemic clearance following intravenous (IV) administration in nonclinical species and humans. LEN formulated in an aqueous suspension or a PEG/water solution formulation showed sustained plasma exposure levels with no unintended rapid drug release following subcutaneous (SC) administration to rats and dogs. A high total fraction dose release was observed with both formulations. The long-acting pharmacokinetics (PK) were recapitulated in humans following SC administration of both formulations. The SC PK profiles displayed two-phase absorption kinetics in both animals and humans with an initial fast-release absorption phase, followed by a slow-release absorption phase. Noncompartmental and compartmental analyses informed the LEN systemic input rate from the SC depot and exit rate from the body. Modeling-enabled deconvolution of the input rates from two processes: absorption of the soluble fraction (minor) from a direct fast-release process leading to the early PK phase and absorption of the precipitated fraction (major) from an indirect slow-release process leading to the later PK phase. LEN SC PK showed flip-flop kinetics due to the input rate being substantially slower than the systemic exit rate. LEN input rates via the slow-release process in humans were slower than those in both rats and dogs. Overall, the combination of high potency, exceptional stability, and optimal release rate from the injection depot make LEN well suited for a parenteral long-acting formulation that can be administered once up to every 6 months in humans for the prevention and treatment of HIV-1.

Ecosystem-based fishery management that accounts for trade-offs between fishing and enhancement stocking: A case study of Juehua Island in the Bohai Sea

The implementation of marine ecosystem management requires modeling that accounts for the trade-off between exploitation in fisheries and protection activities (e.g., enhancement and release, artificial reefs). Researchers are increasingly interested in the trends of fishery resources under these joint driving forces due to the negative impacts of resource exploitation and the positive impacts of marine protection. Using the sea around Juehua Island in China’s Bohai Sea as a case study, we developed a marine ecosystem model based on the Ecopath with Ecosim software to analyze the trends in fishery resources driven both by fishing and stock enhancement. When the fishing effort exceeded 42 % of the 2019 value, the biomass of top predator Platycephalus indicus decreased by 50 %, indicating a regime shift. When the fishing effort increased to 340 % of the 2019 level, the ecosystem shifts to an alternative stable state occurs, indicating destabilization of the marine ecosystem. The impact of fishing effort on the marine ecosystem was not well compensated by release of a single target species. We also designed an orthogonal experiment with three factors (the key species Fenneropenaeus chinensis, Paralichthys olivaceus, and Charybdis japonica) and four restocking release levels to determine both the optimal release rate for each species individually and the optimal combination of different species. If the 2019 fishing effort is maintained, the release of 125 × 106 juvenile F. chinensis, 400 × 103 juvenile P. olivaceus, and 15 × 106 juvenile C. japonica would be an optimal solution to improve the marine biomass, trophic level, and biodiversity. Our results provide insights into ecosystem-based management strategies for implementing a policy to limit fishing in the study area and for scientifically determining the restocking release rates.

Investigation of the Release Rate of Biocide and Corrosion Resistance of Vinyl-, Acrylic-, and Epoxy-Based Antifouling Paints on Steel in Marine Infrastructures.

This study comprehensively assesses the release rate of biocides, corrosion effects related to antifouling, and the physical properties of different paint types. Tests were conducted to measure thickness, viscosity, hardness, bending, adhesion, gloss, impact resistance, abrasion resistance, scratch resistance, polarization, and salt spray. The paints evaluated include resin-based, acrylic-based, epoxy-based, and vinyl-based formulations. The study investigates the influence of biocide content, biocide particle size, and immersion time on release rate using a lab-scale setup. Results showed that acrylic-based paints had a higher biocide release rate due to faster hydrolysis, while smaller biocide particle sizes led to higher release rates in resin-based paints. Optimal total biocide contents were determined to be 30% for acrylic-based, 60% for epoxy-based, and 50% for vinyl-based paints. Antifouling corrosion analysis demonstrated that sample with an optimal release rate effectively prevent algae growth and fouling. Acrylic-based paint with 30 wt.% biocide content exhibited superior adhesion with a dolly separation force of 4.12 MPa. Evaluating the impact of synthesized polyaniline on 30 wt.% epoxy-based paint, a sample coated with 10 wt.% polyaniline represented a low corrosion rate of 0.35 µm/year and a high impedance value of approximately 37,000 Ohm·cm-2.

Green construction and release mechanism of lignin-based double-layer coated urea

BackgroundLignin played an important role in the establishment of coated fertilizers coating material as a substitute for petrochemical raw materials. However, so far, the lignin-based coated fertilizers was limited in only the poor slow-release performance. To achieve good slow-release performance of lignin-based coated fertilizers, hydrophilic of lignin need to be resolved to establish an green and better controllable lignin-based coated fertilizers.ResultsIn the study, a novel green double layer coating with lignin-based polyurethane (LPU) as the inner coating and epoxy resin (EP) as the outer coating was effectively constructed for coated urea. Fourier transform infrared spectra confirmed that lignin and polycaprolactone diol successfully reacted with Hexamethylene diisocyanate. The loss weight and water contact angle (WCA, 75.6–63.6°) of the LPUs decreased with the increased lignin content. The average particle hardness of the lignin-based double-layer coated urea (LDCU) first increased from 58.1 N (lignin of 30%) to 67.0 N (lignin of 60%), but then decreased to 62.3 N (lignin of 70%). The release longevity of the coated urea was closely related to the preparation parameters of the coating material. The optimal cumulative nutrient release rate (79.4%) of LDCU was obtained (lignin of 50%, –CNO/–OH molar ratios of 1.15, EP of 35%, and coating ratio of 5%). The aggregates of hydrone on the LDCU caused the dissolution and swelling of nutrients, and then the diffusion of nutrients through the concentration gradient.ConclusionsA though the nutrient release of the LDCUs was affected by many factors, the successful development of the LDCUs will help improve the rapid development of the coated fertilizer industry.

Concept of rapid and controllable combustion for high power-density diesel engines

Over recent years, the demand to abate global carbon emissions has attracted significant interest and resulted in more stringent policies and regulations. For diesel engines, the fundamental solution to addressing carbon emissions entails optimizing the thermal efficiency. However, for high power-density marine diesel engines, large amount of injection mass companied with little intake swirl makes further optimization of fuel consumption quite difficult. To address this issue, a concept for rapid and controllable combustion is proposed herein. The concept is a theory-based method to design and optimize the combustion system in a forward direction from theory to control method. The concept of rapid combustion relies on the optimization of the combustion process based on ideal Sabathe-Miller cycle to get the optimal heat release rate. The concept of controllable combustion was conducted by theoretically relating the in-cylinder spray evolution with heat release rate so as to determine the controllable parameters of combustion system. The concept proposed was validated by the computational fluid dynamics simulation as well as a high power-density diesel engine with a cylinder power of 450 kW and displacement of 18.9L which has been optimized by traditional benchmark and design of experiments method. The results showed that, the optimization method suggested is reliable to define the combustion system to achieve thermal efficiency as high as possible under the boundary constrains. Moreover, without excessive requirement for turbocharger capacity and injection system, both the fuel consumption and NOx emission decrease under all tested loads by using the proposed method, when compared to the results of traditional optimization method. For the commonly-used 100 % and 75 % load, the fuel consumption respectively drops from 199.02 to 196.5 and 199.75 to 197.15 g/kWh, and NOx emission is reduced by 22 % and 12.6 %, which is relatively remarkable for high power-density marine diesel engines. Therefore, it offers the advantage of significantly reducing the workload when designing and optimizing the combustion of diesel engines.

Evaluating Islatravir Administered Via Microneedle Array Patch for Long-Acting HIV Pre-exposure Prophylaxis Using Physiologically Based Pharmacokinetic Modelling.

Technologies for long-acting administration of antiretrovirals (ARVs) for the prevention and treatment of HIV are at the forefront of research initiatives aiming to tackle issues surrounding drug adherence with the current standard of once-daily oral administration. Islatravir (ISL) is an emerging ARV that shows promising characteristics for long-acting prevention and treatment both orally as well as through alternative routes of administration. Microneedle array patches (MAPs) are a pain-free and discreet transdermal delivery technology that offer extended-release administration of nanoparticulate drugs. This study aimed to utilise physiologically based pharmacokinetic (PBPK) modelling to predict the pharmacokinetics resulting from ISL administered via MAP and to identify key MAP characteristics required to sustain effective concentrations over extended dosing intervals. A PBPK model describing the conversion of ISL to ISL-triphosphate (ISL-TP) and its whole-body disposition was developed and verified against observed clinical data for orally administered ISL in healthy adults. An intradermal PBPK model was integrated with the ISL PBPK model to predict the dose and nanoparticle release rate required for MAP administration strategies capable of achieving a minimum ISL-TP target concentration of 0.05 pmol/106 PBMCs over extended dosing intervals. MAP design was limited to a maximum therapeutic area of 20 cm2 with a dose loading of 4.09 mg/cm2 and a minimum duration of 3 months. Due to the lack of available clinical data, a range of nanoparticle release rates and MAP bioavailability scenarios were simulated to provide an overview of potential clinical outcomes. The ISL PBPK model was successfully verified, with predicted vs observed ratios falling within 0.5-2-fold. ISL MAP doses ranging from 15 to 80 mg were predicted to sustain ISL-TP concentrations above the minimum target concentration at 3, 6 and 12 months after administration. Nanoparticle release rate and MAP bioavailability were found to have a major impact on whether dosing strategies achieved the criteria. Minimum doses of 15 mg and 60 mg with a nanoparticle release rate of 0.0005 h-1 and bioavailability ranging from 25 to 100% were predicted to achieve effective ISL-TP concentrations up to 3 and 6 months, respectively. Doses of 15 mg and 30 mg with a nanoparticle release rate of 0.0005 h-1 were also able to attain the target concentration up to 6 months after MAP administration, albeit with a minimum bioavailability of 75% and 50%, respectively. Furthermore, when simulating a bioavailability of 100%, an 80 mg ISL MAP was predicted to sustain ISL-TP concentrations above the minimum target concentration up to 12 months after administration. The ISL PBPK model successfully predicted ISL and ISL-TP pharmacokinetics across a range of orally administered regimens. The integrated intradermal PBPK model outlined optimal MAP dose and nanoparticle release rates for effective ISL-TP concentrations up to 12 months, providing justification for further investigation of ISL as a candidate for MAP administration.

Effect of gelling agent and penetration enhancer on the release rate of ibuprofen-PEG 6000 solid dispersion from gel preparations

Introduction: Ibuprofen is a non-steriodal anti-inflammatory drug which shows low bioavailability. For gel preparations it is important to increase the release rate of ibuprofen by using solid dispersion systems. Objective: To obtain the optimum release rate of ibuprofen-PEG 6000 solid dispersion from gel, by optimising the gelling agent and the penetrating enhancers. Method: Determination of gelling agent was carried out by comparing the ibuprofen release flux. The gel formulation with the best release flux will be used in the determination of penetrating enhancer to obtain the optimum release flux, by using a two-factor factorial design. Result: HPMC showed the highest release flux (339.5 g/cm2min). The results showed an increase in the release flux (489.4 g/cm2min) in the optimum formula with 39.9% propylene glycol and 3.3% isopropyl myristate. Conclusion: The increase in the ibuprofen solid dispersion release flux has been carried out using HPMC, and propylene glycol-isopropyl myristate as a penetrating enhancer.

"Smart" Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy.

Bacterial infections are a severe medical problem, especially in traumatology, orthopedics, and surgery. The local use of antibiotics-elution materials has made it possible to increase the effectiveness of acute infections treatment. However, the infection prevention problem remains unresolved. Here, we demonstrate the fabrication of polylactic acid (PLA) “smart” films with microchamber arrays. These microchambers contain ceftriaxone as a payload in concentrations ranging from 12 ± 1 μg/cm2 to 38 ± 8 μg/cm2, depending on the patterned film thickness formed by the different PLA concentrations in chloroform. In addition, the release profile of the antibiotic can be prolonged up to 72 h in saline. At the same time, on the surface of agar plates, the antibiotic release time increases up to 96 h, which has been confirmed by the growth suppression of the Staphylococcus aureus bacteria. The efficient loading and optimal release rate are obtained for patterned films formed by the 1.5 wt % PLA in chloroform. The films produced from 1.5 and 2 wt % PLA solutions (thickness—0.42 ± 0.12 and 0.68 ± 0.16 µm, respectively) show an accelerated ceftriaxone release upon the trigger of the therapeutic ultrasound, which impacted as an expansion of the bacterial growth inhibition zone around the samples. Combining prolonged drug elution with the on-demand release ability of large cargo amount opens up new approaches for personalized and custom-tunable antibacterial therapy.

The Release of Fertilizer on Corncob Cellulose – Based Acid-Acrylamide Hydrogel Prepared by Chemical Cross-Binding Method

Farmers' knowledge of the amount and dosage of fertilizers recommended for a practical fertilization system is low. As the result, the plant does not fully absorb the given fertilizer. Some fertilizers are leached by the flowing water and wasted into the soil layer. In long term basis, this practice can cause environmental pollution, especially on the land, water and air. Due to this fertilization problem in agriculture practice, a material with a high-water absorption capacity, which further releases it together with the fertilizer over a desirable period of time, is needed. One way to effectively provide water and nutrients to the plants and improve the physical and chemical properties of the fertilizzer is by the application of hydrogel. In this work, the release of urea fertilizer in a hydrogel-based on corncob cellulose was prepared using N, N'-Methylene Bis-acrylamide (MBA) as a crosslinker was studied. This research aims to produce a hydrogel with good physical and mechanical properties using acrylamide based on corn cobs cellulose and can be applied as a fertilizer carrier matrix whose structure can regulate fertilizer release. The treatments tested were MBA concentrations of 0%, 1%, and 2%, while the ratio of cellulose: solvent was 1: 2 and the addition of urea fertilizer with a concentration of 5%. The results showed that the swelling value increased with increasing acrylamide in the treatment ratio of the concentration of cellulose: acrylamide-acrylamide (NS: AAm). Fertilizer factors also gave a good swelling value. This shows that the addition of fertilizers gives maximum results. The hydrogel with the best treatment, namely the concentration ratio of 1% MBA, produced a swelling value of 7633.3%, a gel fraction of 76.51%, 1.73 miligram fertilizer loading, fertilizer release by 2.9%, a hardness of 7,865 N, with the morphology showing urea crystals in the form of white spots and showing the results of a slow but optimum release rate of fertilizer so that it can be applied for agriculture that requires a lot of nutrients at the beginning of growth.Keywords: corncorb; cellulose; hydrogel; N’,N’-Methylene Bis-acrylamide (MBA), slow released fertilizer

Molecular Mechanism of Ultrasound-Induced Structural Defects in Liposomes: A Nonequilibrium Molecular Dynamics Simulation Study

The use of ultrasound in combination with liposomes is a promising approach to improve drug delivery. To achieve an optimal drug release rate, it is important to understand how ultrasound induces pathways on the liposome surface where drugs can be released from the liposome. To this end, we carry out large-scale ultrasound-induced molecular dynamics simulations for three single lipid component liposomes formed from the commonly used phospholipids: 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoylphosphatidylcholine (DPPC), or phosphatidylcholine (POPC). The results show that ultrasound induces the detachment of two leaflets of the DOPC surface, suggesting that the drug release pathway may be through the low lipid packing areas on the stretched surface. In contrast, ultrasound induces pore formation on the surface of DPPC and DOPC, where drugs could escape from the liposomes. While the leaflet detachment and transient pore formation are the mechanisms of DOPC and DPPC, respectively, in both liquid-ordered and liquid-disordered phases, the leaflet detachment mechanism is switched to the transient pore formation mechanism on going from the liquid-ordered phase to the liquid-disordered phase in the POPC liposome. By adding 30% mol cholesterol, the leaflet detachment mechanism is observed in all liposomes. We found that the molecular origin that determines a mechanism is the competition between the intraleaflet and interleaflet interacting energy of lipids. The connection to experimental and theoretical modeling is discussed in some detail.

Potential Aphid Population Regulation by Aphidius colemani (Hymenoptera: Aphidiidae) in Response to Host Density, Parasitoid Density, and Age.

Aphidius colemani Viereck is an important parasitoid of green peach aphid [Myzus persicae (Sulzer)], a serious pest of greenhouse crops. Augmentation of natural enemies is the most used approach to biological control of greenhouse pests. Yet, the optimal release time, rate, and age of natural enemies are often unclear. Here we tested the influence of population density of both A. colemani and M. persicae, as well as parasitoid age, on parasitism and sex allocation. We aim is to provide information for cost-effective aphid biological control programs. We show that 1) parasitoid females increased parasitism and produced more female-biased offspring with an increase of aphid density, 2) a moderate increase of parasitoid release rate elevated parasitism and daughter production when aphid density was high, 3) parasitism rate declined with an increase of aphid density but the moderate increase of parasitoid release rate eased the decline rate, and 4) 3-d-old parasitoids parasitized more aphids than younger ones but parasitoid age had no effect on daughter production. These findings suggest that A. colemani females can adjust their ability to regulate the aphid population in response to aphid population dynamics. In augmentative programs, a moderate increase of parasitoid release when aphid density is high could achieve effective control and a release of 3-d-old parasitoids could lead to a better control outcome.

Treatment of petroleum hydrocarbon-polluted groundwater with innovative in situ sulfate-releasing biobarrier

Petroleum hydrocarbons are commonly found pollutants in groundwater at industrial and gas station sites. Enhanced bioremediation is a cost-effective approach to cleanup petroleum hydrocarbon-polluted groundwater. The applicability of using sulfate-reducing biobarrier on the containment and control of petroleum-hydrocarbon plumes were assessed by batch and column studies. The innovative in situ biobarrier contained sulfate-releasing materials (SRMs) for a long-term sulfate release to enhance anaerobic petroleum hydrocarbons biodegradation with sulfate reduction mechanisms. SRMs were developed by blending rice husk powder (or starch) (used as permeability increment materials), magnesium sulfate (used as a source of sulfate), and polylactic acid (PLA) (used as a binder) together using a kneader. The mixed components were smelted to form pasty liquid at 190 °C, and it was transferred to a cylinder container to form SRMs. A column study was used to investigate the effectiveness of developed SRMs on the treatment of a methyl tert-butyl ether (MTBE) and toluene contaminated groundwater. The optimal sulfate release rate was achieved when the mass ratio of sulfate/starch/PLA was 0.5/0.5/2 [sulfate release rate (mg.d−1.g−1) = −0.009 × release period (d) + 3.4 (mg). Approximately 70% of MTBE and 92% of toluene could be remediated via sulfate reduction processes because the released sulfate from SRMs were served as electron acceptors, which promoted the growth of sulfate reducers. The next generation sequencing data suggest that bacterial strains with sulfate reduction and petroleum hydrocarbon biodegradation functions were detected after SRM supplement. Evidences of sulfate reduction of toluene and MTBE included (1) increased concentrations of sulfate and sulfide, (2) decreased concentrations of toluene and MTBE, (3) production of tert-butyl alcohol (degradation byproduct of MTBE), and (4) increased sulfate-reducing and petroleum-hydrocarbon bacteria. The biobarrier system containing the SRMs can be developed into a pragmatic technology for in situ remediation of petroleum-hydrocarbon plumes.

Design and optimisation of dendrimer-conjugated Bcl-2/xL inhibitor, AZD0466, with improved therapeutic index for cancer therapy

Dual Bcl-2/Bcl-xL inhibitors are expected to deliver therapeutic benefit in many haematological and solid malignancies, however, their use is limited by tolerability issues. AZD4320, a potent dual Bcl-2/Bcl-xL inhibitor, has shown good efficacy however had dose limiting cardiovascular toxicity in preclinical species, coupled with challenging physicochemical properties, which prevented its clinical development. Here, we describe the design and development of AZD0466, a drug-dendrimer conjugate, where AZD4320 is chemically conjugated to a PEGylated poly-lysine dendrimer. Mathematical modelling was employed to determine the optimal release rate of the drug from the dendrimer for maximal therapeutic index in terms of preclinical anti-tumour efficacy and cardiovascular tolerability. The optimised candidate is shown to be efficacious and better tolerated in preclinical models compared with AZD4320 alone. The AZD4320-dendrimer conjugate (AZD0466) identified, through mathematical modelling, has resulted in an improved therapeutic index and thus enabled progression of this promising dual Bcl-2/Bcl-xL inhibitor into clinical development.

폭발위험장소 설정 시 인화성액체 누출률의 최적 산정방법 연구

In order to determine the extent to which explosion-proof devices should be used in case of leakage in industrial sites handling flammable gases and flammable liquids, the calculation for classification of hazardous area should be carried out. At this time, the Korean Industrial Standard KS C 60079-10-1 citing IEC 60079-10-1, which is an international standard applied, is widely used. However, since the proposed liquid release rate equation does not clearly suggest a method of calculating the amount of vaporized, the calculation process is complicated, or excessive or insufficient results are induced. In order to improve this point, we propose an optimal liquid release rate calculation method, simplify the calculation process, and propose a practical and reasonable method.

A review of controlling strategies of the ignition timing and combustion phase in homogeneous charge compression ignition (HCCI) engine

Generally, the homogeneous charge compression ignition (HCCI) engine presents superior fuel economy and ultra-low NOx and particle matter emissions compared with the traditional combustion engine. However, the HCCI engine is essentially decoupled from the spark plug and fuel injection. That means the HCCI engine has no direct control mechanism for the auto-ignition timing and subsequent combustion phase. Without effective strategies to control the auto-ignition timing on time according to the operating conditions, the HCCI engine will be limited in a small operation range due to the cold start problem, high pressure rate and combustion noise, and even knocking combustion at the high-load. Generally, the properties of physical–chemical kinetics of fuels, as well as the mixture temperature spatial and temporal changing histories in the cylinder, strongly determine the ignition timing and affect the combustion phase in HCCI engine. Some effective techniques and controlling strategies, such as fuel management, homogeneous charge preparation, exhaust gas recirculation, etc. are widely used in the HCCI engine. These techniques and controlling strategies are used solely or conjunctively with each other to control the compressed gas temperature, pressure and mixture distribution in the cylinder at the end of the compression stroke so that the charge mixture could be auto-ignited at the desired crank angle, and thereby obtaining optimal combustion phase and heat release rate on a wide operation range for the HCCI engine. Thus, this paper comprehensively reviews different effective techniques and controlling strategies used in the HCCI engine, and also summarizes in the tables.

Shear Speed-Regulated Properties of Long-Acting Docetaxel Control Release Poly (Lactic-Co-Glycolic Acid) Microspheres.

Advanced drug carriers for the controlled release of chemotherapeutics in the treatment of malignant tumors have drawn significant notice in recent years. In the current study, microspheres (MPs) loaded with docetaxel (DTX) were prepared using polylactic-co-glycolic acid copolymer (PLGA). The double emulsion solvent evaporation method is simple to perform, and results in high encapsulation efficiency. Electron micrographs of the MPs showed that controlling the shear rate can effectively control the size of the MPs. At present, most DTX sustained-release carriers cannot maintain stable and long-term local drug release. The 1.68 μm DTX-loaded microspheres (MP/DTX) with elastase was completely degraded in 14 d. This controlled degradation period is similar to a course of treatment for most cancers. The drug release profile of all kinds of MP/DTX demonstrated an initial rapid release, then slower and stable release to the end. The current study demonstrates that it is possible to create drug-loaded MPs with specific degradation times and drug release curves, which may be useful in achieving optimal treatment times and drug release rates for different diseases, and different drug delivery routes. The initial burst release reaches the effective concentration of the drug at the beginning of release, and then the drug concentration is maintained by stable release to reduce the number of injections and improve patient compliance.

Modelling the intradermal delivery of microneedle array patches for long-acting antiretrovirals using PBPK

IntroductionExisting HIV therapy using oral antiretrovirals (ARVs) can result in pill fatigue and sub-optimal adherence. Microneedle array patches (MAPs) offer non-invasive, blood-free and painless drug delivery, and may improve patient adherence. The objective of this study was to develop a novel physiologically-based pharmacokinetic (PBPK) model to simulate the systemic pharmacokinetics of cabotegravir and rilpivirine MAPs using the intradermal route. MethodsThe developed PBPK models were qualified against observed pharmacokinetic data after intramuscular (IM) and intradermal administration of long-acting nanoformulated rilpivirine to rats, and for IM administration of both drugs to healthy adults. Qualified models were then utilised to estimate suitable MAP characteristics (e.g. nanoformulation dose and release rates) and inform dosing strategies to maintain plasma concentrations above target trough concentrations for the designated dosing interval. ResultsPBPK models simulated q4-weekly loading and maintenance doses of 360 mg and 180 mg for long-acting formulated cabotegravir between the release rates of 1 × 10−3–3 × 10−3h−1 and 1 × 10−3–1.5 × 10−3h−1 respectively, for a 70 kg adult. Estimated patch size was 60 cm2 for a 360 mg dose of cabotegravir. For q4-weekly dosing, rilpivirine required a 1080 mg loading dose and a 540 mg maintenance dose with release rates of 1.5 × 10−3–2.5 × 10−3h−1 and 5 × 10−4–1 × 10−3h−1, respectively. Weekly dosing was also evaluated to assess the potential application from a smaller patch size. The ability to self-administer via a patch that is only left in place for a short duration makes longer durations less important than for some other long-acting approaches. Weekly cabotegravir required 60 mg between release rates 7 × 10−3–9 × 10−3h−1 and rilpivirine required 270 mg and 180 mg respectively between release rates of 7 × 10−3–9 × 10−3h−1. DiscussionThis model estimated optimal dose and release rates for cabotegravir and rilpivirine MAPs. Our approach provides a computational platform to support rational development of intradermal administration strategies to tackle problems associated with chronic oral ARV administration.