Module-combinatorial design and screening of multifunctional polymers based on polyaspartic acid for DNA delivery.

It is crucial to develop non-viral gene vectors that can efficiently and safely transfect plasmid DNA into cells. Low transfection efficiency and high cytotoxicity of cationic polymers hinder their application as gene carriers. Modification of cationic polymers has emerged as an attractive strategy for efficient and safe nucleic acids delivery. In this study, a simple and rapid method is developed to synthesize a series of multifunctional polymers by utilizing biodegradable polyaspartic acid as the backbone and modifying it with three modules. This one-component polymer possesses capabilities for nucleic acid condensation, cellular uptake, and endosomal escape. Polymers containing imidazole, triazole, or pyridine group exhibited promising transfection activity. Substituted with dodecylamine or 2-hexyldecan-1-amine enhance cellular uptake and subsequent transfection. Furthermore, the influence of ionizable amine side chains on gene delivery is investigated. Two optimal polymers, combined with the avian encephalomyelitis virus (AEV) plasmid vaccine, induced robust specific antibody responses and cellular immune responses in mice and chickens. Through module-combination design and screening of polyaspartamide polymers, this study presents a paradigm for the development of gene delivery vectors.

Immuno-Enhancing Effect of Ginsenoside Rh2 Liposomes on Foot-and-Mouth Disease Vaccine.

The adjuvant is essential for vaccines because it can enhance or directly induce a strong immune response associated with vaccine antigens. Ginsenoside Rh2 (Rh2) had immunomodulatory effects but was limited by poor solubility and hemolysis. In this study, Rh2 liposomes (Rh2-L) were prepared by ethanol injection methods. The Rh2-L effectively dispersed in a double emulsion adjuvant system to form a Water-in-Oil-in-Water (W/O/W) emulsion and had no hemolysis. The physicochemical properties of the adjuvants were tested, and the immune activity and auxiliary effects indicated by the Foot-and-Mouth disease (FMDV) antigen were evaluated. Compared with the mice vaccinated with the FMD vaccine prepared with the double emulsion adjuvant alone, those with the FMD vaccine prepared with the double emulsion adjuvant containing Rh2-L had significantly higher neutralizing antibody titer and splenocyte proliferation rates and showed higher cellular and humoral immune responses. The results demonstrated that Rh2-L could further enhance the immune effect of the double emulsion adjuvant against Foot-and-Mouth Disease.

Evaluation the injectability of injectable microparticle delivery systems on the basis of injection force and discharged rate.

BACKGROUND: Subcutaneous injection of biopharmaceutical agents or microparticles is challenging due to issues with low injection efficiency and high residual amounts. OBJECTIVE: This study aimed to determine the important factors affecting the injectability of microparticle delivery systems, establish a suitable injection system with lower injection force and higher discharge rate, and eventually develop a reliable injectability evaluation system for injectable microparticle delivery systems in vitro and in vivo. METHODS: The effects of various parameters, including particle size, injection speed, concentration of microspheres suspension, vehicle viscosity, needle length and gauge were evaluated by measuring the injection force and discharge rate. The characteristics of microparticles and rheological measurement of the suspension systems were studied. A design of experiment approach was utilized to evaluate the interaction between the microsphere suspension, vehicle viscosity and needle gauges. Both in vitro sieve tests and in vivo tests in rats were conducted to evaluate injectability. RESULTS: The in vitro test results showed that the vehicle viscosity and injection speed have varying effects on discharge rate and injection force, respectively. Particle size and needle gauge have substantial influence on injectability, larger particle size and smaller needle gauges resulting in poor injectability, while the needle gauge was found to have the greatest influence on injectability. Levonorgestrel (LNG) microsphere and glass bead were relatively uniform spherical, the glass bead had extremely smooth surface; while mesoporous silica had irregular shape. The settling rate of glass bead was the fastest, which was about 18 times faster than the LNG microsphere. The CMC-Na had a poor interaction with the LNG microspheres, glass bead and mesoporous silica and showed basically Newtonian behavior in the shear rate range of 0.1 s-1-100 s-1. When shear rate increased to more than 100 s-1, no obvious shear thinning behavior was observed. CMC-Na formed a nodule structure with whether LNG microspheres or the glass beads, which were much lower than that with the mesoporous silica in static state, among which the glass beads were the weakest. The viscosity of the suspension increased with the rising of the volume fraction of particles. Fundamentals of hydrodynamics in capillaries were referenced, such as Navier-Stokes Law equation, Krieger-Dougherty (K-D) equation, Hagen-Poiseuille equation. The best results achieved was using a suspension concentration of 120-240 mg /mL and a viscosity of 60 cP at 20 °C with 23-gauge needles. The optimized conditions were verified in vivo tests. It was proven that the LNG microsphere suspension had a good injectability when injected into subcutaneous tissue of rats. CONCLUSION: The injection system of injectable microparticle delivery system with lower injection force and higher discharge rate was established and the evaluation method was suitable for the injectability evaluation both in vivo and in vitro. Improved injectability would promote the clinical translation of microparticle delivery systems.

Corosolic acid-modified lipid nanoparticles as delivery carriers for DNA vaccines against avian influenza.

Cholesterol (CHOL) is essential for developing lipid nanoparticles (LNPs) for gene delivery because it enhances membrane fusion and improves the delivery efficiency of gene cargos. An attractive pDNA carrier, corosolic acid (CA)-modified lipid nanoparticles (CLNPs), was developed by replacing CHOL in LNPs to deliver pDNA at various ratios of nitrogen groups to phosphate groups (N/P). The resultant CLNPs with a higher CHOL/CA ratio exhibited similar mean particle size, zeta potential, and encapsulation efficiency to those of LNPs. In comparison with LNPs, CLNPs (CHOL:CA ratio = 2:1) achieved increased cellular uptake and enhanced transfection efficacy while maintaining low cytotoxicity. In vivo results from chicken experiments demonstrated that CLNPs encapsulating DNA vaccines against avian influenza at a N/P ratio of 3 could elicit similar-level humoral and cellular immune responses compared with those of LNPs at a higher N/P ratio, thereby suggesting the induction of desirable immune effects using less ionizable lipids. Our study provides a reference for further research on the application of CA in LNPs for gene delivery, and the development of novel delivery systems for DNA vaccines against avian influenza.

Stabilizing Effect of Soluplus on Erlotinib Metastable Crystal Form in Microparticles and Amorphous Solid Dispersions.

Microparticles (MPs) and amorphous solid dispersions (SDs) are effective methods to improve the dissolution of insoluble drugs. However, stability is a concern for these two high-energy systems, resulting from high surface area and amorphous polymorph, respectively. As an amphiphilic polymer, Soluplus (SOL) is usually used as a carrier in SDs. In this study, erlotinib microparticles (ERL MPs) and erlotinib solid dispersions (ERL SDs) were prepared with SOL by bottom-up technology and solvent evaporation. The solid-state properties of ERL MPs and ERL SDs were characterized by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The ERL MPs existed in a metastable crystal form A while the ERL SDs existed in an amorphous state. Fourier transform infrared spectroscopy (FT-IR) showed that there was a hydrogen bond interaction between the N-H group of ERL and the carbonyl group of SOL in ERL MPs and SDs. The dissolution profiles of ERL SDs and ERL MPs were improved significantly. ERL MPs showed better stability than ERL SDs in accelerated stability test. The discrepant stabilizing effects of polymer SOL in two systems may provide effective ideas for solubilization of insoluble drugs and the stability of drugs after recrystallization.

Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment.

Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers. However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported. Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death. For example, T24 cells were treated with 12 µM CBD for 48 h, flow cytometry analysis demonstrated that early and late apoptotic cells were accounted for by 49.91%, indicating CBD enhanced cell apoptosis ability. To deeper explore molecular mechanisms, the CBD-treated T24 cell transcriptome libraries were established. KEGG analysis implied that the significantly changed genes were enriched in the PI3K/Akt pathway. qRT-PCR and Western blot assays verified that CBD regulated BC cells growth and migration and induced apoptosis by inactivating the PI3K/Akt pathway. Meanwhile, the developed chitosan to wrap CBD-loaded PLGA nanoparticles can significantly enhance the adhesion of the material to the mouse bladder wall, and the binding efficiency of mucin to chitosan-PLGA nanoparticles reached 97.04% ± 1.90%. In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.

Photothermal therapy enhance the anti-mitochondrial metabolism effect of lonidamine to renal cell carcinoma in homologous-targeted nanosystem.

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with poor prognosis. Therapeutic drugs for RCC can easily develop resistance or have unignorable toxicity or limited efficiency. Here, the thermosensitive mitochondrial metabolism-interfering anticancer drug lonidamine (LND) was combined with the photothermal material polydopamine (PDA) to treat RCC. To delivery drugs accurately to RCC site, LND and PDA were loaded in stellate mesoporous silica nanoparticles (MSNs) with a large surface area and cloaked with RCC membranes (MLP@M). The results showed that MLP@M exhibited excellent tumor targeting ability. The synergistic effects of LND and PDA in MLP@M were greatly enhanced when triggered by an 808 nm laser. Moreover, the antiproliferative and tumor suppressing abilities were enhanced with good biocompatibility after MLP@M + laser treatment. Additionally, 80% of RCC tumor-bearing mice treated with MLP@M + laser did not relapse. Our study provides a potential therapeutic approach for RCC treatment.

PEGylated-PLGA Nanoparticles Coated with pH-Responsive Tannic Acid-Fe(III) Complexes for Reduced Premature Doxorubicin Release and Enhanced Targeting in Breast Cancer.

Biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been widely used as delivery vehicles for chemotherapy drugs. However, premature drug release in PLGA NPs can damage healthy tissue and cause serious adverse effects during systemic administration. Here, we report a tannic acid-Fe(III) (FeIII-TA) complex-modified PLGA nanoparticle platform (DOX-TPLGA NPs) for the tumor-targeted delivery of doxorubicin (DOX). A PEGylated-PLGA inner core and FeIII-TA complex outer shell were simultaneously introduced to reduce premature drug release in blood circulation and increase pH-triggered drug release in tumor tissue. Compared to the unmodified NPs, the initial burst rate of DOX-TPLGA NPs was significantly reduced by nearly 2-fold at pH 7.4. Moreover, the cumulative drug release rate at pH 5.0 was 40% greater than that at pH 7.4 due to the pH-response of the FeIII-TA complex. Cellular studies revealed that the TPLGA NPs had enhanced drug uptake and superior cytotoxicity of breast cancer cells in comparison to free DOX. Additionally, the DOX-TPLGA NPs efficiently accumulated in the tumor site of 4T1-bearing nude mice due to the enhanced permeability and retention (EPR) effect and reached a tumor inhibition rate of 85.53 ± 8.77% (1.31-fold versus DOX-PLGA NPs and 3.12-fold versus free DOX). Consequently, the novel TPLGA NPs represent a promising delivery platform to enhance the safety and efficacy of chemotherapy drugs.

A Novel Drug Delivery Carrier Comprised of Nimodipine Drug Solution and a Nanoemulsion: Preparation, Characterization, in vitro, and in vivo Studies.

PURPOSE: Nimodipine (NIMO) is used clinically to treat ischemic damage resulting from subarachnoid hemorrhage. However, clinical application of NIMO is limited by poor aqueous solubility and low safety. To overcome these limitations, a novel two-vial NIMO-loaded nanoemulsion (NIMO-TNE) was designed in this study. METHODS: NIMO-TNE was prepared by mixing a nimodipine-polyethylene glycol 400 (NIMO-PEG400) solution and a commercially available 20% injectable blank nanoemulsion (BNE). Drug distribution in NIMO-TNE, physical stability, and dilution stability were evaluated in vitro, and pharmacokinetics and pharmacodynamics were evaluated in vivo. Safety was assessed using the hemolysis test and the intravenous irritation test, and acute toxicity of NIMO-TNE was compared with that of commercial Nimotop injection. RESULTS: Drug loading (DL) in NIMO-TNE was enhanced 5-fold compared with that in Nimotop injection. The mean particle size of NIMO-TNE was 241.53 ± 1.48 nm. NIMO-TNE and NIMO-TNE diluted in 5% glucose injection and 0.9% sodium chloride was stable for a sufficient duration to allow for clinical use. In addition, NIMO-TNE exhibited a similar pharmacokinetic profile and similar brain ischemia reduction in a rat middle cerebral artery occlusion (MCAO) model compared to Nimotop injection. Furthermore, NIMO-TNE did not induce hemolysis at 37°C, and NIMO-TNE induced less intravenous irritation than Nimotop injection. Moreover, NIMO-TNE could be injected at a 23-fold higher dose than the LD50 of Nimotop injection with no obvious toxicity or side effects. CONCLUSION: NIMO-TNE is a promising formulation suitable for intravenous injection, is easy to prepare, and exhibits excellent safety.

Predicting physical stability of solid dispersions by machine learning techniques.

Amorphous solid dispersion (SD) is an effective solubilization technique for water-insoluble drugs. However, physical stability issue of solid dispersions still heavily hindered the development of this technique. Traditional stability experiments need to be tested at least three to six months, which is time-consuming and unpredictable. In this research, a novel prediction model for physical stability of solid dispersion formulations was developed by machine learning techniques. 646 stability data points were collected and described by over 20 molecular descriptors. All data was classified into the training set (60%), validation set (20%), and testing set (20%) by the improved maximum dissimilarity algorithm (MD-FIS). Eight machine learning approaches were compared and random forest (RF) model achieved the best prediction accuracy (82.5%). Moreover, the RF models revealed the contribution of each input parameter, which provided us the theoretical guidance for solid dispersion formulations. Furthermore, the prediction model was confirmed by physical stability experiments of 17ß-estradiol (ED)-PVP solid dispersions and the molecular mechanism was investigated by molecular modeling technique. In conclusion, an intelligent model was developed for the prediction of physical stability of solid dispersions, which benefit the rational formulation design of this technique. The integrated experimental, theoretical, modeling and data-driven AI methodology is also able to be used for future formulation development of other dosage forms.

Investigating molecular interactions of high-loaded glipizide-HPMCAS microparticles by integrated experimental and modeling techniques.

Molecular interactions between drug and polymeric carriers are believed to be the key for high drug loading and better physical stability of micro-particles. However, molecular interactions between drug and polymer are still difficult to investigate using only experimental tools. In this study, high-loaded glipizide (GLP)/hydroxypropyl methylcellulose acetate succinate (HPMCAS) (1/1 w/w) micro-particles were prepared using an in situ pH-dependent solubility method. Molecular interactions within the micro-particles were investigated by integrated experimental and modeling techniques. The dissolution rate of GLP/HPMCAS micro-particles was significantly better than those of solid dispersions and physical mixtures. Scanning electron microscopy images showed that the polymer inhibited GLP recrystallization. Experimental (FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction and nuclear magnetic resonance spectroscopy) and molecular dynamics simulation revealed that hydrogen-bonding was the key to the properties of the micro-particles. Our research developed high drug-loading GLP/HPMCAS micro-particles and investigated the interactions between drug and polymer at the molecular level. This integrated approach could be practical methodology for future formulation design.

Codelivery of miR-4638-5p and Docetaxel Based on Redox-Sensitive Polypeptide Micelles as an Improved Strategy for the Treatment of Castration-Resistant Prostate Cancer.

In this work, we have developed a reducible, self-assembling disulfide cross-linked and peptide-based micelle system for codelivery of miR-4638-5p and DTX to improve the efficacy of castration-resistant prostate cancer (CRPC) therapy. The result showed that DTX in micelles (DTX-VPs) inhibited cell growth and induced apoptosis more effectively than free DTX both in vitro and in vivo. In addition, the DTX and miR-4638-5p loaded micelles (Co-VPs) achieved the most pronounced anticancer effect of all groups. Immunohistochemical analysis indicated that miR-4638-5p in micelle system could effectively downregulate the expression of Kidins220 and further improve the anticancer effect by enhancing tumor cell apoptosis and suppressing tumor cell proliferation. Finally, the bioimaging analysis demonstrated that DIR in micelles (DIR-VPs) showed a higher concentration and a longer retention time in tumor tissue than did free DIR, which indicated an excellent tumor-targeting ability of the micelle system. All these results suggest that codelivery of miR-4638-5p and DTX via polypeptide micelle system has a potential for CRPC treatment.

Peptide T7-modified polypeptide with disulfide bonds for targeted delivery of plasmid DNA for gene therapy of prostate cancer.

BACKGROUND: Vectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa). METHODS: The structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7-plasmid DNA complex were examined. RESULTS: The results demonstrated that the CRD-PEG-T7-plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG-plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system. CONCLUSION: The results above indicatd that the CRD-PEG-T7-plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor.

Antisolvent Recrystallization Strategy to Screen Appropriate Carriers to Stabilize Filgotinib Amorphous Solid Dispersions.

Drugs in amorphous solid dispersions (ASDs) are highly dispersed in hydrophilic polymeric carriers, which also help to restrain recrystallization and stabilize the ASDs. In this study, microscopic observation after antisolvent recrystallization was developed as a rapid screening method to select appropriate polymers for the initial design filgotinib (FTN) ASDs. Using solvent evaporation, FTN ASDs with the polymers were prepared, and accelerated experimentation validated this screening method. Fourier-transform infrared spectroscopy, Raman scattering, and nuclear magnetic resonance revealed hydrogen-bonding formation in the drug-polymer binary system, which was critical for ASDs stabilization. A Flory-Huggins interaction parameter and water sorption isotherms were applied to evaluate the strength of the interaction between FTN and the polymers. The dissolution rate was also significantly improved by ASDs formulation, and the presence of the polymers exerted solubilization effects. These results suggested the efficacy of this screening method as a preliminary tool for polymer selection in ASDs design.

Screen for Inhibitors of Crystal Growth to Identify Desirable Carriers for Amorphous Solid Dispersions Containing Felodipine.

The solvent-shift method was used to identify appropriate polymers that inhibit the growth of felodipine crystals by monitoring particle size in supersaturated drug solutions in the presence of different polymers. We speculated that there would be an intermolecular interaction between the selected polymer (zein) and felodipine by extrapolating the inhibitory effect on crystal growth and then used the selected polymer as a carrier to prepare solid dispersions. The formulations were characterized by crystalline properties, thermodynamics of mixing, dissolution behavior, and physical stability. Powder x-ray diffraction and differential scanning calorimetry experiments indicated that amorphous solid dispersions were formed when the proportion of felodipine was < 30% (w/w). Stability tests showed that a solid dispersion with 20% felodipine remained in an amorphous state and was stable under accelerated storage conditions for 6 months. The dissolution rates of solid dispersions were significantly greater than those of the active pharmaceutical ingredient or physical mixtures. Analysis by Fourier-transform infrared spectroscopy and Raman microspectroscopy indicated the formation of intermolecular interactions between zein and felodipine. The study demonstrates the successful application of the chosen polymer as a carrier in solid dispersions and validates the concept of extrapolating the inhibitory effect on crystal growth to intermolecular interactions.

Complexes of Felodipine Nanoparticles With Zein Prepared Using a Dual Shift Technique.

To improve the dissolution of felodipine, felodipine-zein complexes were prepared using a dual shift technique, with zein as both stabilizer and carrier. The complexes were characterized by particle size, zeta potential, morphology, crystalline properties, and release behavior. The complexes could be prepared in high yield and showed good redispersibility. The mean diameters of the felodipine particles in complexes were 150-300 nm, with negative zeta potentials of -30 to -25 mV after rehydration, and the particle sizes of the complexes were in the range 10-80 µm. The size of the felodipine nanoparticles incorporated into zein increased gradually with increasing drug content. Powder X-ray diffraction and differential scanning calorimetry indicated that felodipine in the complexes was markedly less crystalline than the pure drug. Both the rate and extent of dissolution of the complexes were significantly greater than those of the active pharmaceutical ingredient or physical mixtures. Spectroscopic analyses indicated that intermolecular interactions, especially hydrophobic interactions, are the major driving forces for the formation of the felodipine nanoparticles and contribute to the stabilization effect. This study provides a promising strategy for enhancing the dissolution rate of drugs using simplified preparation processes and showcases the design of zein-based oral delivery systems for bioactive components.

Improving the physicochemical properties of bicalutamide by complex formation with bovine serum albumin.

Bicalutamide-bovine serum albumin (Bic-BSA) complexes were prepared by anti-solvent precipitation. Bovine serum albumin (BSA) was used as a stabilizer for particle growth. The physicochemical properties of Bic-BSA were analyzed by scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. The interaction between Bic and BSA was characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, fluorescence spectroscopy and molecular docking. The particle size could be easily reduced to 1-10µm with a good lognormal distribution. The Bic-BSA complexes exhibited nonporous spherical morphology with a uniformly plicated surface. Moreover, the crystal form and thermostability of Bic were altered in the presence of BSA. Bic was found to make hydrogen bonding and hydrophobic interactions with BSA by spectroscopic studies and molecular docking. Results from the Van't Hoff equation and binding free energy calculations indicated that the improvement of physicochemical properties was the consequence of a variety of interactions in the Bic-BSA system. Bic-BSA tablets showed significantly enhanced dissolution. It was concluded that BSA plays an important role in improving the physicochemical properties of Bic due to strong multiple interactions between Bic and BSA.

The Physicochemical Investigation of 17ß-Estradiol Crystalline Prepared by In Situ pH-Dependent Solubility Technique with Polyvinylpyrrolidone.

Micro-particles of 17ß-estradiol (ED) were prepared with polyvinylpyrrolidone (PVP) by in situ pH-dependent solubility technique. Products were characterized using multiple instruments, and molecular interactions between ED and PVP were explored. Powder X-ray diffraction and thermal analysis revealed crystalline ED in the micro-particles is hemihydrated. PVP was also present in the micro-particles. Laser particle size analysis and scanning electron microscopy revealed thin slice morphology, which might have resulted from the influence of PVP. Moreover, the results of contact angle, specific surface area, and dynamic vapor sorption showed that the surface properties of products were improved. These physicochemical properties of the micro-particles resulted in an obvious improvement in dissolution rate. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed hydrogen bonding between ED and PVP. A method was established for the preparation of micro-particles through the addition of PVP during the reaction process.

Characterization of ibuprofen microparticle and improvement of the dissolution.

The objective of this study was to prepare ibuprofen (IBP) microparticles by pH-change method and enhance the dissolution rate in vitro. Tween80 and Cremophor RH40 were selected as stabilizers to change the microparticles morphology. The microparticles were evaluated by dissolution profiles and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), laser particle size analyzer, scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). IBP microparticle prepared with surfactants showed a significant increase in dissolution rate (more than three times within 10 min) and an obvious decrease in mean particle size. The morphology of microparticles was obviously changed. XRD and DSC results revealed that the crystalline state of the untreated IBP and the prepared IBP microparticles were similar. The crystallinity of microparticles produced might be lightly reduced by adding surfactants in preparation process. All results showed that it was useful to prepare high dispersion microparticle by adding surfactants in the preparation process for improving the dissolution.