Mechanistic Analysis of Temperature-Dependent Curcumin Release from Poly(lactic-co-glycolic acid)/Poly(lactic acid) Polymer Nanoparticles.

In this study, we investigated the mechanism of curcumin (CUR) release from poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) nanoparticles (NPs) by evaluating the temperature-dependent CUR release. NPs were prepared by the nanoprecipitation method using various PLGA/PLA polymers with different lactic:glycolic ratios (L:G ratios) and molecular weights. Increasing the polymer molecular weight resulted in a decrease in the particle size of NPs. The wet glass transition temperature (Tg) of PLGA/PLA NPs was lower than the intrinsic polymer Tg, which can be derived from the water absorption and nanosizing of the polymer. The reduction in Tg was more significant for the PLGA/PLA NPs with lower polymer L:G ratios and lower polymer molecular weight. The greater decrease of Tg in the lower polymer L:G ratios was possibly caused by the higher water absorption due to the more hydrophilic nature of the glycolic acid segment than that of the lactic acid segment. The efficient water absorption in PLGA/PLA NPs with lower molecular weight could cause a significant reduction of Tg as it has lower hydrophobicity. CUR release tests from the PLGA/PLA NPs exhibited enhanced CUR release with increasing temperatures, irrespective of polymer species. By fitting the CUR release profiles into mathematical models, the CUR release process was well described by an initial burst release followed by a diffusion-controlled release. The wet Tg and particle size of the PLGA/PLA NPs affected the amount and temperature dependence of the initial burst release of CUR. Above the wet Tg of NPs, the initial burst release of CUR increased sharply. Smaller particle sizes of PLGA/PLA NPs led to a higher fraction of initial CUR burst release, which was more pronounced above the wet Tg of NPs. The wet Tg and particle sizes of the PLGA/PLA NPs also influenced the diffusion-controlled CUR release. The diffusion rate of CUR in the NPs increased as the wet Tg values of the NPs decreased. The diffusion path length of CUR was affected by the particle size, with larger particle size resulting in a prolonged diffusion-controlled release of CUR. This study highlighted that for the formulation development of PLGA/PLA NPs, suitable PLGA/PLA polymers should be selected considering the physicochemical properties of PLGA/PLA NPs and their correlation with the release behavior of encapsulated drugs at the application temperature.

Dissolution Mechanisms of Amorphous Solid Dispersions: Application of Ternary Phase Diagrams To Explain Release Behavior.

The use of amorphous solid dispersions (ASDs) in commercial drug products has increased in recent years due to the large number of poorly soluble drugs in the pharmaceutical pipeline. However, the release behavior of ASDs is complex and remains not well understood. Often, the drug release from ASDs is rapid and complete at lower drug loadings (DLs) but becomes slow and incomplete at higher DLs. The DL where release becomes hindered is termed the limit of congruency (LoC). Currently, there are no approaches to predict the LoC. However, recent findings show that one potential cause leading to the LoC is a change in phase morphology after water-induced phase separation at the ASD/solution interface. In this study, the phase behavior of ASDs in contact with aqueous solutions was described thermodynamically by constructing experimental and computational ternary phase diagrams, and these were used to predict morphology changes and ultimately the LoC. Experimental ternary phase diagrams were obtained by equilibrating ASD/water mixtures over time. Computational ternary phase diagrams were obtained by Perturbed Chain Statistical Associating Fluid Theory (PC-SAFT). The morphology of the hydrophobic phase was studied with fluorescence confocal microscopy. It was demonstrated that critical point (plait point) composition approximately corresponded to the ASD DL, where the hydrophobic phase, formed during phase separation, became interconnected and hindered ASD release. This work provides mechanistic insights into the ASD release behavior and highlights the potential of in silico ASD design using phase diagrams.

A potential slow-release fertilizer based on biogas residue biochar: Nutrient release patterns and synergistic mechanism for improving soil fertility.

The large yield of anaerobic digestates and the suboptimal efficacy of nutrient slow-release severely limit its practical application. To address these issues, a new biochar based fertilizer (MAP@BRC) was developed using biogas residue biochar (BRC) to recover nitrogen and phosphorus from biogas slurry. The nutrient release patterns of MAP@BRC and mechanisms for enhancing soil fertility were studied, and it demonstrated excellent performance, with 59% total nitrogen and 50% total phosphorus nutrient release rates within 28 days. This was attributed to the coupling of the mechanism involving the dissolution of struvite skeletons and the release of biochar pores. Pot experiments showed that crop yield and water productivity were doubled in the MAP@BRC group compared with unfertilized planting. The application of MAP@BRC also improved soil nutrient levels, reduced soil acidification, increased microbial populations, and decreased soil heavy metal pollution risk. The key factors that contributed to the improvement in soil fertility by MAP@BRC were an increase in available nitrogen and the optimization of pH levels in the soil. Overall, MAP@BRC is a safe, slow-release fertilizer that exhibits biochar-fertilizer interactions and synergistic effects. This slow-release fertilizer was prepared by treating a phosphorus-rich biogas slurry with a nitrogen-rich biogas slurry, and it simultaneously addresses problems associated with livestock waste treatment and provides a promising strategy to promote zero-waste agriculture.

Phycocyanin-Loaded Alginate-Based Hydrogel Synthesis and Characterization.

Phycocyanin was extracted from Spirulina platensis using conventional extraction (CE), direct ultrasonic-assisted extraction (direct UAE), indirect ultrasonic-assisted extraction (indirect UAE), and microwave-assisted extraction (MAE) methods at different temperatures, extraction intervals, stirring rate, and power intensities while maintaining the same algae to solvent ratio (1:15 w/v). The optimization of the extraction parameters indicated that the direct UAE yielded the highest phycocyanin concentration (29.31 ± 0.33 mg/mL) and antioxidant activity (23.6 ± 0.56 mg TE/g algae), while MAE achieved the highest purity (Rp = 0.5 ± 0.002). Based on the RP value, phycocyanin extract obtained by MAE (1:15 w/v algae to solvent ratio, 40 min, 40 °C, and 900 rpm) was selected as active compound in an alginate-based hydrogel formulation designed as potential wound dressings. Phycocyanin extracts and loaded hydrogels were characterized by FT-IR analysis. SEM analysis confirmed a porous structure for both blank and phycocyanin loaded hydrogels, while the mechanical properties remained approximately unchanged in the presence of phycocyanin. Phycocyanin release kinetics was investigated at two pH values using Zero-order, First-order, Higuchi, and Korsmeyer-Peppas kinetics models. The Higuchi model best fitted the experimental results. The R2 value at higher pH was nearly 1, indicating a superior fit compared with lower pH values.

Different Drug Mobilities in Hydrophobic Cavities of Host-Guest Complexes between ß-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water.

Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between ß-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between ß-CD and 5-FU. Both 1:1 and 1:2 ß-CD/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 1:2 ß-CD/5-FU complexes, the intermolecular interactions affect the drug's mobility, suggesting a two-step release mechanism: a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the ß-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.

Chalkophomycin Biosynthesis Revealing Unique Enzyme Architecture for a Hybrid Nonribosomal Peptide Synthetase and Polyketide Synthase.

Chalkophomycin is a novel chalkophore with antibiotic activities isolated from Streptomyces sp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation of N-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into one compact molecular architecture capable of coordinating cupric ions draws interest to unprecedented enzymology responsible for chalkophomycin biosynthesis. To elucidate the biosynthetic machinery for chalkophomycin production, the chm biosynthetic gene cluster from S. sp. CB00271 was identified, and its involvement in chalkophomycin biosynthesis was confirmed by gene replacement. The chm cluster was localized to a ~31 kb DNA region, consisting of 19 open reading frames that encode five nonribosomal peptide synthetases (ChmHIJLO), one modular polyketide synthase (ChmP), six tailoring enzymes (ChmFGMNQR), two regulatory proteins (ChmAB), and four resistance proteins (ChmA'CDE). A model for chalkophomycin biosynthesis is proposed based on functional assignments from sequence analysis and structure modelling, and is further supported by analogy to over 100 chm-type gene clusters in public databases. Our studies thus set the stage to fully investigate chalkophomycin biosynthesis and to engineer chalkophomycin analogues through a synthetic biology approach.

Application of essential oils as slow-release antimicrobial agents in food preservation: Preparation strategies, release mechanisms and application cases.

Food spoilage caused by foodborne microorganisms will not only cause significant economic losses, but also the toxins produced by some microorganisms will also pose a serious threat to human health. Essential oil (EOs) has significant antimicrobial activity, but its application in the field of food preservation is limited because of its volatile, insoluble in water and sensitive to light and heat. Therefore, in order to solve these problems effectively, this paper first analyzed the antibacterial effect of EOs as an antimicrobial agent on foodborne bacteria and its mechanism. Then, the application strategies of EOs as a sustained-release antimicrobial agent in food preservation were reviewed. On this basis, the release mechanism and application cases of EOs in different antibacterial composites were analyzed. The purpose of this paper is to provide technical support and solutions for the preparation of new antibacterial packaging materials based on plant active components to ensure food safety and reduce food waste.

Release Behavior of Liquid Crystal Monomers from Waste Smartphone Screens: Occurrence, Distribution, and Mechanistic Modeling.

Liquid crystal display (LCD) screens can release many organic pollutants into the indoor environment, including liquid crystal monomers (LCMs), which have been proposed as a novel class of emerging pollutants. Knowing the release pathways and mechanisms of LCMs from various components of LCD screens is important to accurately assess the LCM release and reveal their environmental transport behavior and fate in the ambient environment. A total of 47, 43, and 33 out of 64 target LCMs were detected in three disassembled parts of waste smartphone screens, including the LCM layer (LL), light guide plate (LGP), and screen protector (SP), respectively. Correlation analysis confirmed LL was the source of LCMs detected in LGP and SP. The emission factors of LCMs from waste screen, SP, and LGP parts were estimated as 2.38 × 10-3, 1.36 × 10-3, and 1.02 × 10-3, respectively. A mechanism model was developed to describe the release behaviors of LCMs from waste screens, where three characteristics parameters of released LCMs, including average mass proportion (AP), predicted subcooled vapor pressures (PL), and octanol-air partitioning coefficients (Koa), involving coexistence of absorption and adsorption mechanisms, could control the diffusion-partitioning. The released LCMs in LGP could reach diffusion-partition equilibrium more quickly than those in SP, indicating that LCM release could be mainly governed through SP diffusions.

Starfish oocytes of A. pectinifera reveal marked differences in sperm-induced electrical and intracellular calcium changes during oocyte maturation and at fertilization.

Although changes in membrane potential and intracellular Ca2+ (Cai ) during fertilization in starfish oocytes have been known for long time, little is known precisely about how and what kind of channels are involved during oocyte maturation and in fertilization, and how the mechanisms of changes in Cai in oocytes develop during oocyte maturation. Since in starfish, oocyte maturation-inducing hormone, 1-methyladenine (1MA) is well known, we took advantage of it to investigate the developmental process of channel-function and changes in Cai in three different developmental stages using 1MA. Sperm-induced membrane current at voltage clamp and changes in Cai in starfish oocytes, Asterina pectinifera, were examined in stages of immature, partly mature (a state in 15-20 min after sufficient concentration, 1 µM of 1MA addition, or 30-40 min exposure to subthreshold concentration of 1MA), and mature oocytes (MO). We found some immature and many partly MOs showed fluctuating responses in membrane current, membrane potential, and corresponding changes in Cai , which are distinct from those in MOs. The responses in immature and partly MOs indicate physiologically characteristic responses of insufficient changes in Cai and its corresponding electrical responses at the partial developmental stage during maturation. Our data should shed light on the mechanism of egg activation and oocyte maturation in terms of examining membrane current and corresponding changes in Cai .

Recent advances in essential oil complex coacervation by efficient physical field technology: A review of enhancing efficient and quality attributes.

Although complex coacervation could improve the water solubility, thermal stability, bioavailability, antioxidant activity and antibacterial activity of essential oils (EOs). However, some wall materials (such as proteins and polysaccharides) with water solubility and hydrophobic nature limited their application in complex coacervation. In order to improve the properties of EO complex coacervates, some efficient physical field technology was proposed. This paper summarizes the application and functional properties of EOs in complex coacervates, formation and controlled-release mechanism, as well as functions of EO complex coacervates. In particular, efficient physical field technology as innovative technology, such as high pressure, ultrasound, cold plasma, pulsed electric fields, electrohydrodynamic atomization and microwave technology improved efficient and quality attributes of EO complex coacervates are reviewed. The physical fields could modify the gelling, structural, textural, emulsifying, rheological properties, solubility of wall material (proteins and polysaccharides), which improve the properties of EO complex coacervates. Overall, EOs complex coacervates possess great potential to be used in the food industry, including high bioavailability, excellent antioxidant capacity and gut microbiota in vivo, masking the sensation of off-taste or flavor, favorable antimicrobial capacity.

Porous Crosslinked Zwitterionic Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole as Possible Drug Delivery Systems.

Crosslinked porous microparticles have received great attention as drug delivery systems lately due to their unique set of properties: the capability to form various polymer-drug combinations, low immunogenicity, patient compliance and ability to release drugs in a delayed or controlled manner. Moreover, polymers with betaine groups have shown some unique features such as antifouling, antimicrobial activity, biocompatibility and strong hydration properties. Herein, novel porous zwitterionic microparticles were prepared in two stages. The first step involves the synthesis of porous microparticles based on glycidyl methacrylate, N-vinylimidazole and triethyleneglycol dimethacrylate using the suspension polymerization technique, the second step being the synthesis of zwitterionic porous microparticles by polymer-analogous reaction in presence of sodium monochloroacetate as betainization agent. Both types of microparticles were characterized structurally and morphologically by FT-IR spectroscopy, energy dispersive X-ray analysis, scanning electron microscopy, dynamic vapors sorption and mercury porosimetry. The tetracycline loading into crosslinked and zwitterionic microparticles was also performed, the maximum tetracycline loading capacities being 87 mg/g and 135 mg/g, respectively. The drug release mechanism, elucidated by various mathematical models, is controlled by both diffusion and swelling processes as a function of the zwitterionic and/or porous microparticle structure. Both types of microparticles presented antibacterial activity against the two reference strains used in this study: Escherichia coli and Staphylococcus aureus.

Physico-Chemical and Antimicrobial Efficacy of Encapsulated Dhavana Oil: Evaluation of Release and Stability Profile from Base Matrices.

Essential oils (EOs) are naturally occurring volatile aromatic compounds extracted from different parts of plants. They are made up of components like terpenes, phenols, etc., and are chemically unstable and susceptible to oxidative deterioration, leading to reduced shelf-life and overall degradation of the product. Encapsulation of EOs in a matrix can prevent degradation of the active ingredient and improve the shelf-life. In this paper, we report encapsulation of Dhavana oil (Artemisia pellen) in a modified starch matrix using a spray-drying technique. Physico-chemical properties of neat and encapsulated Dhavana oil were studied. We selected two powder bases: CaCO3 and TALC and, loaded neat and encapsulated Dhavana oil in it, studied their stability and interaction with the base matrices at 3 °C, 22 °C and 45 °C up to 2 months under closed conditions and one week at 22 °C and 45 °C under open condition. Thermal degradation pattern was studied for neat and encapsulated Dhavana oil and modified starch. Release of primary active component of neat and encapsulated Dhavana oil from the base matrices was evaluated with GCMS. Stability study and release mechanism were elucidated to understand the release pattern in different base powders under similar conditions. Retention of hydroxydhavanone was found to be better in TALC than CaCO3, and therefore, the former can be considered a suitable base matrix for developing a stable powder formulation with an optimum release of the oil. Dhavana oil is known for its anti-microbial activity, and hence, neat and encapsulated Dhavana oil was tested on different bacterial and fungal strains. The encapsulated oil depicted good anti-microbial efficacy against various bacterial and fungal strains, which is a step forward for developing anti-microbial formulations. Thus, the reported work will provide helpful information on cosmetic formulation and, therefore, be useful for perfumery, food, and cosmetic industries.

Insights into the release mechanisms of antioxidants from nanoemulsion droplets.

The therapeutic effects of antioxidant-loaded nanoemulsion can be often optimized by controlling the release rate in human body. Release kinetic models can be used to predict the release profile of antioxidant compounds and allow identification of key parameters that affect the release rate. It is known that one of the critical aspects in establishing a reliable release kinetic model is to understand the underlying release mechanisms. Presently, the underlying release mechanisms of antioxidants from nanoemulsion droplets are not yet fully understood. In this context, this review scrutinized the current formulation strategies to encapsulate antioxidant compounds and provide an outlook into the future of this research area by elucidating possible release mechanisms of antioxidant compounds from nanoemulsion system.

Description of Release Process of Doxorubicin from Modified Carbon Nanotubes.

The article discusses the release process of doxorubicin hydrochloride (DOX) from multi-wall carbon nanotubes (MWCNTs). The studies described a probable mechanism of release and actions between the surface of functionalized MWCNTs and anticancer drugs. The surface of carbon nanotubes (CNTs) has been modified via treatment in nitric acid to optimize the adsorption and release process. The modification efficiency and physicochemical properties of the MWCNTs+DOX system were analyzed by using SEM, TEM, EDS, FTIR, Raman Spectroscopy and UV-Vis methods. Based on computer simulations at pH 7.4 and the experiment at pH 5.4, the kinetics and the mechanism of DOX release from MWNT were discussed. It has been experimentally observed that the acidic pH (5.4) is appropriate for the efficient release of the drug from CNTs. It was noted that under acidic pH conditions, which is typical for the tumour microenvironment almost 90% of the drug was released in a relatively short time. The kinetics models based on different mathematical functions were used to describe the release mechanism of drugs from MWCNTs. Our studies indicated that the best fit of experimental kinetic curves of release has been observed for the Power-law model and the fitted parameters suggest that the drug release mechanism of DOX from MWCNTs is controlled by Fickian diffusion. Molecular dynamics simulations, on the other hand, have shown that in a neutral pH solution, which is close to the blood pH, the release process does not occur keeping the aggregation level constant. The presented studies have shown that MWCNTs are promising carriers of anticancer drugs that, depending on the surface modification, can exhibit different adsorption mechanisms and release.

Design and evaluation of a zero-order controlled release system based on pre-hydrated constant release area prepared by compression coating technology.

The main aim of this research work was to develop and evaluate a drug delivery system with compression coating technology to control drug release at a constant rate. The compression coated tablets (CCTs) consist of the hydrophilic matrix core and the hydrophobic waxy coating. The presence of hydrophobic waxy coating could provide sufficient time for hydration of the core to prevent initial burst release. The mechanism research revealed that erosion was the main way of drug release and the releasing area was constant during the entire release process because the core tablet was located in the cup-shaped coating after one side cover was dropped at the lag time. This made the release behavior exhibit zero-order kinetics (R2>0.99). The coating rupture strength and the core swelling force at the lag time influenced erosion rate thus affecting release rate. Different solubility of drugs (propranolol hydrochloride, melatonin, and nifedipine) was selected as model drugs and the properties of the prepared CCTs in terms of formulations and in vitro release were evaluated. The release rate was independent of solubility, medium pH, and osmotic pressure. This zero-order controlled system could be applied to both controlled drug delivery and chrono pharmaceutical drug delivery.

New insights into the release mechanism of Cd2+ from CdTe quantum dots within single cells in situ.

Cadmium-quantum dots (Cd-QDs) possess unique properties as optoelectronic devices for sensitive detection in food and biomedicine fields. However, the toxic effects of Cd-QDs to single cells is still controversial, due to the release mechanism of QDs to Cd2+in situ and the cytotoxic effects of QDs and Cd2+ respectively are still unclear. In this paper, the release rule of Cd2+ from CdTe QDs within single cells was investigated in situ by using flow cytometry method and the dose-response relationships were explored. Besides, an all-inclusive microscopy system was optimized for live cell imaging to observe the real-time entry process of CdTe QDs into cells. We found that intracellular CdTe QDs and Cd2+ contents were increased based on the dosage and exposing time. A dissociated saturation of Cd2+ from CdTe QDs was exist within cells. CdTe QDs induced more serious cytotoxicity on kidney cells than hepatocytes. The toxicity of oxidative stress, cell apoptosis effects induced by CdTe QDs and Cd2+ are also in consistent with this result. This research develops analytical method to quantify the uptake and release of Cd-QDs to primary cells in situ and can provide technical support in studying the cytotoxicity portion contributed by nanoparticles (NPs) and metal ions.

Preparation and tribological behaviour of poly(methyl methacrylate) (PMMA) microcapsules containing friction modifiers.

Aims: Microcapsules comprising of a poly(methyl methacrylate) (PMMA) shell and friction modifier (FM) core were prepared to reduce the friction and extend the service life of engine lubricating oil.Methods: Microcapsules containing both organic FM and molybdenum FM were produced via solvent evaporation technique. The friction coefficient, thermal stability, and chemical composition of microcapsules were investigated.Results: The incorporation of microcapsules in lubricating oil dramatically reduced the friction coefficient to be lower than that of virgin FM. Organic FM and molybdenum FM are compatible during the encapsulation process. The release of the FM inside the microcapsules was controllable by thermal degradation of polymeric shell at 150 °C or mechanical rupture at room temperature.Conclusions: This study provided a novel approach to improve the tribological properties of lubricating oil with long service life, facile fabrication and low cost and will find potential applications in lubrication industry for internal combustion engines.

An Analytic Investigation of the Drug Formulation-Based Recalls in the USA: See More Beyond the Literal.

High numbers of drug recalls persist despite the tremendous time and effort invested by pharmaceutical organizations and regulatory bodies such as the Food and Drug Administration (FDA) to ensure the quality of safe and effective medicines for the patient. It is imperative to better understand the underlying risk factors of drug formulation-based recalls to best protect the patient from poor quality drugs. Increased knowledge of underlying factors of formulation risk can also help inform the future design and development of drugs. In this study, we used a text mining technique with Python to parse the data and examine drug recalls from the aspect of administration route, dosage form, release mechanism, market type, pharmacologic class, and excipients. Observational analysis of the recalls revealed both high- and low-risk factors for the formulation-based recalls. Higher risk, or an increased probability of a formulation-based recall, was associated with factors such as extended release mechanism, capsule dosage form, oral route of administration, and an increased number of excipients, while lower risk of formulation-based recalls was associated with other factors including the new drug application market type, immediate release mechanism, and solution dosage form. In addition, the factors did not work independently, and we observed interactions among variables. For example, the release mechanism modified the effect of market type, administration route, and dosage form. This study will help inform the future design of quality drug products by pharmaceutical organizations and assist risk-based oversight by regulatory organizations, such as FDA, to ensure patient safety.

[Preparation of Cangyi nanoemulsion in situ gel and drug release mechanism of nasal mucosa in vitro].

To prepare Cangyi nanoemulsion in situ gel and study its nasal mucosa release mechanism in vitro. After proper treatment of different drugs in the compound, the prescription of nanoemulsion was determined by pseudo-ternary phase diagram method. With the ratio of mixed emulsifier to oil phase [(S+COS)/O], the ratio of mixed emulsifier(K_m), the ratio of water phase to mixed emulsifier and oil phase[W/(S+COS+O)] as investigation factors and the normalized value(OD) as evaluation index, the prescription of Cangyi nanoemulsion was optimized by central composite design-response surface method. With the ratio of poloxamer 407(P407) and poloxamer 188(P188) as the investigation factors and the gelation temperature as the evaluation index, the in situ gel prescription of Cangyi nanoemulsion was optimized. The improved Franz diffusion cell was used to explore the nasal mucosa drug-release mechanism of Cangyi nanoemulsion in situ gel with oxymatrine, ferulic acid and salvianolic acid B content as indexes. The optimal prescription of Cangyi nanoemulsion in situ gel was as follows: 6.862% castor oil polyoxyl(EL), 4.262% absolute ethanol, 1.392% ethyl oleate, 7% P407 and 6% P188. The average pH was 5.55 and the average gelation temperature was 32.8 ℃. In vitro release studies showed that oxymatrine, ferulic acid and salvianolic acid B were released simultaneously and the drug release behavior was consistent with that in Higuchi model. The preparation process of Cangyi nanoemulsion in situ gel is stable, with suitable pH value, gelation temperature and viscosity. It has a certain slow-release effect, and can meet the needs of local nasal drug use.

Modification of Three-Phase Drug Release Mode of Octreotide PLGA Microspheres by Microsphere-Gel Composite System.

In order to obtain sustained release of biodegradable microspheres, the purpose of this study was to design and characterize an injectable octreotide microsphere-gel composite system. The octreotide microspheres were prepared by phase separation method, which used PLGA as a carrier material, dimethyl silicone oil as a phase separation reagent, and n-heptane-Span 80 as a hardener. In addition, we used poloxamer 407 (PL 407) and poloxamer 188 (PL 188) as the thermosensitive gel matrix material. The composite system was obtained by scattering octreotide microspheres in a poloxamer gel. In vitro data showed that the release time of the composite system could last for about 50 days. Because of the blocking and control actions of the poloxamer gel, the initial burst release was significantly reduced and the plateau phase was eliminated. Pharmacokinetic data showed that the burst release of the composite system was significantly less than that of the microspheres, i.e., Cmax1 was reduced by about half. From day 2 to day 50, higher plasma concentration levels and more stable drug release behavior were exhibited. In addition, the good biocompatibility of the composite system in vivo was also demonstrated by hematoxylin-eosin (HE) staining. Therefore, the octreotide microsphere-gel composite system will be a new direction for hydrophilic polypeptide/protein-loaded sustained release dosage forms with high pharmacological activity.