Mutations in the FOXO3 Gene and Their Effects on Meat Traits in Gannan Yaks.

The FOXO3 gene, a prominent member of the FOXO family, has been identified as a potential quantitative trait locus for muscle atrophy and lipid metabolism in livestock. It is also considered a promising candidate gene for meat quality traits such as Warner-Bratzler shear force (WBSF) and water holding capacity (WHC). The aim of this study was to identify sequence mutations in the FOXO3 gene of yaks and to analyze the association of genotypes and haplotypes with meat traits such as WBSF and WHC. Quantitative reverse-transcriptase PCR (RT-qPCR) was applied to determine the expression levels of FOXO3 in yak tissues, with the results revealing a high expression in the yak longissimus dorsi muscle. Exons of the FOXO3 gene were then sequenced in 572 yaks using hybrid pool sequencing. Five single nucleotide polymorphisms were identified. Additionally, four effective haplotypes and four combined haplotypes were constructed. Two mutations of the FOXO3 gene, namely C>G at exon g.636 and A>G at exon g.1296, were associated with cooked meat percentage (CMP) (p < 0.05) and WBSF (p < 0.05), respectively. Furthermore, the WBSF of the H2H3 haplotype combination was significantly lower than that of other combinations (p < 0.05). The findings of this study suggest that genetic variations in FOXO3 could be a promising biomarker for improving yak meat traits.

Variation in Acetyl-CoA Carboxylase Beta Gene and Its Effect on Carcass and Meat Traits in Gannan Yaks.

Acetyl-CoA carboxylase beta (ACACB) is a functional candidate gene that impacts fat deposition. In the present study, we sequenced exon 37-intron 37, exon 46-intron 46, and intron 47 of yak ACACB using hybrid pool sequencing to search for variants and genotyped the gene in 593 Gannan yaks via Kompetitive allele-specific polymerase chain (KASP) reaction to determine the effect of ACACB variants on carcass and meat quality traits. Seven single nucleotide polymorphisms were detected in three regions. Eight effective haplotypes and ten diplotypes were constructed. Among them, a missense variation g.50421 A > G was identified in exon 37 of ACACB, resulting in an amino acid shift from serine to glycine. Correlation analysis revealed that this variation was associated with the cooking loss rate and yak carcass weight (p = 0.024 and 0.012, respectively). The presence of haplotypes H5 and H6 decreased Warner-Bratzler shear force (p = 0.049 and 0.006, respectively), whereas that of haplotypes H3 and H4 increased cooking loss rate and eye muscle area (p = 0.004 and 0.034, respectively). Moreover, the presence of haplotype H8 decreased the drip loss rate (p = 0.019). The presence of one and two copies of haplotypes H1 and H8 decreased the drip loss rate (p = 0.028 and 0.004, respectively). However, haplotype H1 did not decrease hot carcass weight (p = 0.011), whereas H3 increased the cooking loss rate (p = 0.007). The presence of one and two copies of haplotype H6 decreased Warner-Bratzler shear force (p = 0.014). The findings of the present study suggest that genetic variations in ACACB can be a preferable biomarker for improving yak meat quality.

Inhalable Nanocomposite Microparticles with Enhanced Dissolution and Superior Aerosol Performance.

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×ρtapped" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.

The practical self-targeted oncolytic adenoviral nanosphere based on immuno-obstruction method via polyprotein surface precipitation technique enhances transfection efficiency for virotherapy.

Recent developments in tumour treatment had focused on virotherapies that were currently revolutionising new innovated treatment pathways. This study focused on the fabrication of oncolytic adenoviral vector (Ad) nanosphere that self-targeted at lung tumour cells (A549), utilising the immune response for upper respiratory tract infection, caused by the Ad infection. This system was dependent upon T-cell immune response, surface charge and blood metabolism. Oncolytic Ad attacked lung A549 tumour cells by incorporated its own DNA to replace A549's, the triggered immune response generated T-cells also further attack A549. Direct Ad injection was demonstrated to be lethal and prohibited in vivo. In this research a multifunctional principal using polyprotein surface precipitation technique (PSP) whist maintaining biological controls for self-assembly polyprotein Ad nanosphere both biocompatible and reproducible, was demonstrated as a result of the enhanced transfection efficiency and a successful multifunctional drug delivery system for virotherapy.

Silk fibroin nanoparticles for enhanced bio-macromolecule delivery to the retina.

The aim of this study was to investigate intravitreal injection of silk fibroin nanoparticles (SFNs) encapsulating bio-macromolecules, achieving enhanced drug bioavailability, and extended retention in retina. SFNs were prepared with regenerated silk fibroin using desolvation method with fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) as bio-macromolecular model drug encapsulated. In vitro physicochemical properties and in vitro drug release of FITC-BSA loaded SFNs (FITC-BSA-SFNs) were evaluated. Cytotoxicity, cellular uptake, and retention of FITC-BSA-SFNs were determined in human retinal pigment epithelial cell line (ARPE-19). In addition, in vivo distribution and safety of intravitreally administered FITC-BSA-SFNs were investigated in New Zealand white rabbits. The particle size of FITC-BSA-SFNs was 179.1 ± 3.7 nm with polydispersity index of 0.102 ± 0.033 and the zeta potential was greater than -25 mV. FITC-BSA-SFNs exhibited excellent biocompatibility with no cytotoxicity observed within 24 and 48 h in AREP-19 cells. Compared to FITC-BSA solution, FITC-BSA-SFNs showed enhanced cellular uptake and prolonged retention. Furthermore, FITC-BSA-SFNs achieved accumulated distribution and extended retention in retina in vivo following intravitreal injection compared to a single administration of free drug solution. Therefore, this bio-macromolecule delivery platform based on SFNs could have great potential in the treatment of posterior segment disorders.

Formation Mechanism, In vitro and In vivo Evaluation of Dimpled Exenatide Loaded PLGA Microparticles Prepared by Ultra-Fine Particle Processing System.

Spherical poly (D, L-lactic-co-glycolic acid) microparticles (PLGA-MPs) have long been investigated in order to achieve sustained delivery of proteins/peptides. However, the formation mechanism and release characteristics of the specific shape MPs were still unknown. This study aimed to develop a novel-dimpled exenatide-loaded PLGA-MPs (Exe-PLGA-MPs) using an ultra-fine particle processing system (UPPS) and investigate the formation mechanism and release characteristics. Exe-PLGA-MPs were prepared by UPPS and optimized based on their initial burst within the first 24 h and drug release profiles. Physicochemical properties of Exe-PLGA-MPs, including morphology, particle size, and structural integrity of Exe extracted from Exe-PLGA-MPs, were evaluated. Furthermore, pharmacokinetic studies of the optimal formulation were conducted in Sprague-Dawley (SD) rats to establish in vitro-in vivo correlations (IVIVC) of drug release. Exe-PLGA-MPs with dimpled shapes and uniform particle sizes achieved a high encapsulation efficiency (EE%, 91.50 ± 2.65%) and sustained drug release for 2 months in vitro with reduced initial burst (20.42 ± 1.64%). Moreover, the pharmacokinetic studies revealed that effective drug concentration could be maintained for 3 weeks following a single injection of dimpled Exe-PLGA-MPs with high IVIVC. Dimpled PLGA-MPs prepared using the UPPS technique could thus have great potential for sustained delivery of macromolecular proteins/peptides.

Influence of Polymers on the Physical and Chemical Stability of Spray-dried Amorphous Solid Dispersion: Dipyridamole Degradation Induced by Enteric Polymers.

Amorphous solid dispersions (ASDs) are inherently unstable because of high internal energy. Evaluating physical and chemical stability during the process and storage is essential. Numerous researches have demonstrated how polymers influence the drug precipitation and physical stability of ASDs, while the influence of polymers on the chemical stability of ASDs is often overlooked. Therefore, this study aimed to investigate the effect of polymers on the physical and chemical stability of spray-dried ASDs using dipyridamole (DP) as a model drug. Proper polymers were selected by assessing their abilities to inhibit drug recrystallization in supersaturated solutions. HPMC E5, Soluplus®, HPMCP-55, and HPMCAS-LP were shown to be effective stabilizers. The optimized formulations were further stored at a high temperature (60 °C) and high humidity (40 °C, 75% RH) for 2 months, and their physical and chemical stability was evaluated using polarizing optical microscopy, FTIR, HPLC, and mass spectrometry (MS). In general, crystallization was observed in all samples, which indicated the physical instability under stressed storage conditions. Also, it was noted that the polymers in ASDs rather than physical mixtures, induced a dramatic drug degradation after being exposed to a high temperature (HPMCP-55 > 80% and HPMCAS-LP > 50%) and high humidity (HPMCP-55 > 40% and HPMCAS-LP > 10%). The MS analysis further confirmed the degradation products, which might be generated from the reaction between dipyridamole and phthalic anhydride decomposed from HPMCP-55 and HPMCAS-LP. Overall, the exposure of ASDs to stressed conditions resulted in recrystallization and even the chemical degradation induced by polymers.

Evaluation of Streptococcus thermophilus IFFI 6038 Microcapsules Prepared Using an Ultra-fine Particle Processing System.

Microencapsulation technology has the potential to protect probiotics and to deliver them to the gut, and extrusion is one of the most commonly used methods. However, the rather large diameters of 1~5 mm produced tend to cause oral grittiness and result in low compliance. In this article, Streptococcus thermophilus IFFI 6038 (IFFI 6038) microcapsules were prepared using an ultra-fine particle processing system (UPPS) previously developed by this research group. IFFI 6038 suspension was pumped by a peristaltic pump to the feeding inlet nozzle and then dispersed into micro-droplets by a rotating disk, followed by solidification. Trehalose (16%) was used as a cryoprotectant to protect IFFI 6038 from damage by lyophilization used in the process. Alginate (3%) resulted in IFFI 6038 microcapsules with a median particle diameter (d 50) of 29.32 ± 0.12 µm and a span value of 1.00 ± 0.02, indicating uniform particle size distribution. To evaluate the potential of microencapsulation in protecting IFFI 6038 from the gastric conditions, the viable counts of IFFI 6038 following incubation of IFFI 6038 microcapsules in simulated gastric juices for 120 min were determined and compared with those of free IFFI 6038. The stability of microencapsulated IFFI 6038 upon storage for 3 months at 4°C and 25°C, respectively, was also determined. The results showed that microcapsules prepared by UPPS protected IFFI 6038 from gastric conditions. The results from a rat diarrhea model showed that microcapsules prepared by the UPPS method were able to effectively improve the diarrhea conditions in rats.

Comparison of novel granulated pellet-containing tablets and traditional pellet-containing tablets by artificial neural networks.

Novel granulated pellets technique was adopted to prepare granulated pellet-containing tablets (GPCT). GPCT and traditional pellet-containing tablets (PCT) were prepared according to 29 formulations devised by the Design Expert 7.0, with doxycycline hydrochloride as model drug, blends of Eudragit FS 30D and Eudragit L 30D-55 as coating materials, for the comparison study to confirm the superiority of GPCT during compaction. Eudragit FS 30D content, coating weight gain, tablet hardness and pellet size were chosen as influential factors to investigate the properties and drug release behavior of tablets. The correlation coefficients between the experimental values and the predicted values by artificial neural networks (ANNs) for PCT and GPCT were 0.9474 and 0.9843, respectively, indicating the excellent prediction of ANNs. The similarity factors (f2) for release profiles of GPCT and the corresponding original pellets were higher than those of PCT, suggesting that the excipient layer of granulated pellets absorbed the compressing force and protected the integrity of coating films during compaction.

Variation in the HSL Gene and Its Association with Carcass and Meat Quality Traits in Yak.

Hormone-sensitive lipase (HSL) is involved in the breakdown of triacylglycerols in adipose tissue, which influences muscle tenderness and juiciness by affecting the intramuscular fat content (IMF). This study analyzed the association between different genotypes and haplotypes of the yak HSL gene and carcass and meat quality traits. We used hybridization pool sequencing to detect exon 2, exon 8, and intron 3 variants of the yak HSL gene and genotyped 525 Gannan yaks via KASP to analyze the effects of the HSL gene variants on the carcass and meat quality traits in yaks. According to the results, the HSL gene is highly expressed in yak adipose tissue. Three single nucleotide polymorphisms (SNPs) were identified, with 2 of them located in the coding region and one in the intron region. Variants in the 2 coding regions resulted in amino acid changes. The population had 3 genotypes of GG, AG, and AA, and individuals with the AA genotype had lower WBSF values (p < 0.05). The H3H3 haplotype combinations could improve meat tenderness by reducing the WBSF values and the cooking loss rate (CLR) (p < 0.05). H1H1 haplotype combinations were associated with the increased drip loss rate (DLR) (p < 0.05). The presence of the H1 haplotype was associated the increased CLR in yaks, while that of the H2 haplotype was associated with the decreased DLR in yaks (p < 0.05). These results demonstrated that the HSL gene may influence the meat quality traits in yaks by affecting the IMF content in muscle tissues. Consequently, the HSL gene can possibly be used as a biomarker for improving the meat quality traits in yaks in the future.

Long-stranded non-coding RNAs temporal-specific expression profiles reveal longissimus dorsi muscle development and intramuscular fat deposition in Tianzhu white yak.

The process of muscle development and intramuscular fat (IMF) deposition is quite complex and controlled by both mRNAs and ncRNAs. Long-stranded non-coding RNAs (LncRNAs) are involved in various biological processes in mammals while also playing a critical role in muscle development and fat deposition. In the present study, RNA-Seq was used to comprehensively study the expression of lncRNAs and mRNAs during muscle development and intramuscular fat deposition in postnatal Tianzhu white yaks at three stages, including 6 mo of age (calve, n = 6), 30 mo of age (young cattle, n = 6) and 54 mo of age (adult cattle, n = 6). The results indicated that a total of 2,101 lncRNAs and 20,855 mRNAs were screened across the three stages, of which the numbers of differential expression (DE) lncRNAs and DE mRNAs were 289 and 1,339, respectively, and DE lncRNAs were divided into eight different expression patterns based on expression trends. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that some DE mRNAs overlapped with target genes of lncRNAs, such as NEDD4L, SCN3B, AGT, HDAC4, DES, MYH14, KLF15 (muscle development), ACACB, PCK2, LIPE, PIK3R1, PNPLA2, and MGLL (intramuscular fat deposition). These DE mRNAs were significantly enriched in critical muscle development and IMF deposition-related pathways and GO terms, such as AMPK signaling pathway, PI3K-Akt signaling pathway, PPAR signaling pathway, etc. In addition, lncRNA-mRNA co-expression network analysis revealed that six lncRNAs (MSTRG.20152.2, MSTRG.20152.3, XR_001351700.1, MSTRG.8190.1, MSTRG.4827.1, and MSTRG.11486.1) may play a major role in Tianzhu white yak muscle development and lipidosis deposition. Therefore, this study enriches the database of yak lncRNAs and could help to further explore the functions and roles of lncRNAs in different stages of muscle development and intramuscular fat deposition in the Tianzhu white yak.

In-depth analysis of the molecular regulatory mechanisms involved in the development of yak skeletal muscle can aid in the identification of crucial functional genes that may enhance the quality of yak meat in the future. Our research is the first to investigate the expression of long-stranded non-coding RNAs (lncRNAs) during muscle development and intramuscular fat deposition in Tianzhu white yaks at different ages (6, 30, and 54 mo). We have discovered numerous novel lncRNAs and their associated target genes that are linked to muscle development and fat deposition, and have constructed relevant interaction network diagrams. This study is expected to promote a genetics-based approach to further enhance the Tianzhu white yak and other yak breeds.

Engineered lipid liquid crystalline nanoparticles as an inhaled nanoplatform for mucus penetration enhancement.

Nanocarrier-assisted pulmonary drug delivery system has been widely employed for lung local disease treatment due to its enhanced drug lesion accumulation and reduced systematical side effects. However, the mucus barriers covered on the epithelia of trachea and bronchial tree construct a dense barrier for inhaled nanocarrier transport, which compromises the therapeutical effects. In this study, a lipid liquid crystalline nanoparticle NLP@Z with surface zwitterion material hexadecyl betaine (HB) modification and N-acetylcysteine (NAC) encapsulation was presented to exert the combination strategy of mucus-inert surface and mucus degradation. The HB modification endowed NLP@Z mucus-inert surface to inhibit the interaction between NLP@Z and mucins, and the encapsulated NAC could effectively degrade the mucins and further decrease the mucus viscosity. This combination strategy was proved to significantly promote the mucus penetration performance and enhance epithelial cell uptake. In addition, the proposed NLP@Z was equipped with desired nebulization property, which could be served as a potential pulmonary delivery nanoplatform. In summary, the proposed NLP@Z highlights the employment of the combination strategy for mucus penetration enhancement in pulmonary delivery, which may become a versatile platform for lung disease therapy.

In vitro evaluation of drug delivery behavior for inhalable amorphous nanoparticle formulations in a human lung epithelial cell model.

Respiratory tract infections caused by multidrug-resistant (MDR) Gram-negative bacteria such as Pseudomonas aeruginosa are serious burdens to public health, especially in cystic fibrosis patients. The combination of colistin, a cationic polypeptide antibiotic, and ivacaftor, a cystic fibrosis transmembrane regulator (CFTR) protein modulator, displays a synergistic antibacterial effect against P. aeruginosa. The primary aim of the present study is to investigate the transport, accumulation and toxicity of a novel nanoparticle formulation containing colistin and ivacaftor in lung epithelial Calu-3 cells. The cell viability results demonstrated that ivacaftor alone or in combination with colistin in the physical mixture showed significant toxicity at an ivacaftor concentration of 10 µg/mL or higher. However, the cellular toxicity was significantly reduced in the nanoparticle formulation. Ivacaftor transport into the cells reached a plateau rapidly as compared to colistin. Colistin transport across the Calu-3 cell monolayer was less than ivacaftor. A substantial amount (46-83%) of ivacaftor, independent of dose, was accumulated in the cell monolayer following transport from the apical into the basal chamber, whereas the intracellular accumulation of colistin was relatively low (2-15%). The nanoparticle formulation significantly reduced the toxicity of colistin and ivacaftor to Calu-3 cells by reducing the accumulation of both drugs in the cell and potential protective effects by bovine serum albumin (BSA), which could be a promising safer option for the treatment of respiratory infections caused by MDR P. aeruginosa.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor.

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

PLGA microsphere-based composite hydrogel for dual delivery of ciprofloxacin and ginsenoside Rh2 to treat Staphylococcus aureus-induced skin infections.

When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.

Release mechanisms of bovine serum albumin loaded-PLGA microspheres prepared by ultra-fine particle processing system.

The ultra-fine particle processing system (UPPS) previously developed by our lab has been used to prepare various microparticulate formulations. Microspheres prepared by UPPS can achieve sustained release with a reduced initial burst compared to the microspheres prepared by the conventional water-in-oil-in-water (W/O/W) double emulsion technique. However, the in vitro drug release mechanism of the microspheres prepared by UPPS is still uninvestigated. This study aimed to investigate the mechanisms of bovine serum albumin (BSA) released from poly (D,L-lactic-co-glycolic acid) (PLGA) microspheres prepared by UPPS in comparison with microspheres prepared by the W/O/W double emulsion technique. The morphology, in vitro drug release, water uptake, and structural evolution of microspheres prepared by both techniques were evaluated. UPPS microspheres showed solid and compact internal structures without any pores or channels thereby exhibiting a reduced rate of water permeation in the release medium. In addition, the release of BSA in UPPS microspheres was mainly controlled by the erosion of the polymer matrix during the entire process, while BSA was released from W/O/W microspheres by both drug diffusion and matrix erosion. Moreover, the observed surface and internal structural evolution also confirmed their different release mechanisms. This work elaborates the release mechanism of PLGA microspheres prepared by UPPS and facilitates the design of microparticulate formulations. Graphical abstract.

Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release.

This study aimed to prepare poly (D, L-lactic-co-glycolic acid) microspheres (PLGA-Ms) by a modified solid-in-oil-in-water (S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles (Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles (Ex-NPs) via the alcohol injection method, followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water (W/O/W) technique (Ex-PLGA-Ms), Ex-NPs-PLGA-Ms showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity. In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve (AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

Data on the drug release profiles and powder characteristics of the ethyl cellulose based microparticles prepared by the ultra-fine particle processing system.

Ethyl cellulose (EC) based microparticles (MPs) could provide sustained release for Huperzine A. The drug release mechanism of MPs was exploited to achieve an ideal drug release profile. We previously found that the wettability of MPs greatly contributed to facilitating drug release, which was detailed in a research article entitled "Huperzine A loaded multiparticulate disintegrating tablet: Drug release mechanism of ethyl cellulose microparticles and pharmacokinetic study" (Peng et al., 2019) [1]. In this article, the influence of different polymers and drugs on the drug release behavior was investigated to broaden or compensate this finding. Besides, powder characterization of MPs was used to evaluate the further application of MPs for tablets.

Anhydrous reverse micelle lecithin nanoparticles/PLGA composite microspheres for long-term protein delivery with reduced initial burst.

To address the issue of initial burst release from poly (lactic-co-glycolic) acid (PLGA) microspheres prepared by water-in-oil-in-water (W/O/W) double emulsion technique, PLGA composite microspheres containing anhydrous reverse micelle (ARM) lecithin nanoparticles were developed by a modified solid-in-oil-in-water (S/O/W) technique. Bovine serum albumin (BSA) loaded ARM lecithin nanoparticles, which were obtained by initial self-assembly and subsequent lipid inversion of the lecithin vesicles, were then encapsulated into PLGA matrix by the S/O/W technique to form composite microspheres. In vitro release study indicated that BSA was slowly released from the PLGA composite microspheres over 60 days with a reduced initial burst (11.42 ±â€¯2.17% within 24 h). The potential mechanism of reduced initial burst and protein protection using this drug delivery system was analyzed through observing the degradation process of carriers and fitting drug release data with various kinetic models. The secondary structure of encapsulated BSA was well maintained through the steric barrier effect of ARM lecithin nanoparticles, which avoided exposure of proteins to the organic solvent during the preparation procedure. In addition, the PLGA composite microspheres exhibited superior biocompatibility without notable cytotoxicity. These results suggested that ARM lecithin nanoparticles/PLGA composite microspheres could be a promising platform for long-term protein delivery with a reduced initial burst.

Fragmented particles containing octreotide acetate prepared by spray drying technique for dry powder inhalation.

Dry powder inhalers (DPIs) have been proposed as an alternative administration route for protein and peptide drugs. However, DPI particles are easy to aggregate due to the strong interactions between the particles, leading to poor aerosolization performance. In this study, fragmented particles containing octreotide acetate (OA) were prepared by spray drying technique for dry powder inhalation, which were expected to decrease the particle-particle interaction by reducing the contact sites. Mannitol and ammonium carbonate were used as protein stabilizer and fragment-forming agent, respectively. The obtained fragmented particles presented larger particle size, lower density, better dispersibility, and well in vitro aerodynamic behavior (emitted dose > 97%, fine particle fraction ≈ 40%). The circular dichroism spectrum results indicated that OA maintained the stability throughout the spray drying process. The relative bioavailability of dry powder inhalation (DPI) compared with subcutaneous injection of commercial product was up to 88.0%, demonstrating the feasibility of DPI for OA delivery. These results confirmed that the proposed fragmented particles had great potential for pulmonary delivery of protein and peptide drugs in a painless, rapid, and convenient manner.