Microspheres Loading Research Articles

Eco-friendly, pH-sensitive curcumin-loaded sodium alginate/hydroxyapatite/quaternary ammonium chitosan microspheres with enhanced antibacterial and antioxidant activities for fruit preservation

The development of intelligent responsive reactive packaging materials with natural polymers shows excellent potential in food preservation. In this study, eco-friendly, pH-sensitive sodium alginate (SA)/hydroxyapatite (HA)/quaternary ammonium chitosan (HACC) composite microspheres loading curcumin (CUR) with excellent antibacterial and antioxidant activities were successfully synthesized. Scanning electron microscopy (SEM) and nitrogen adsorption/desorption tests indicated that the doping of HA substantially increased the specific surface area and pore volume of the microspheres. The loading experiments showed that the efficiency of the microspheres was significantly increased by 49.47 % and 55.10 %, respectively, when HA and HACC were incorporated into the SA network. The release test results suggested that the release rate of SA/HA/HACC microspheres loading CUR (SA/HA/HACC@CUR) increased as the pH decreased, demonstrating notable pH-responsive release characteristics. DPPH free radical scavenging experiments demonstrated that the SA/HA/HACC@CUR had excellent and long-lasting antioxidant capacity. The antibacterial experiments revealed that the SA/HA/HACC@CUR had excellent antibacterial properties, with inhibition rates of 88.73 % and 92.52 % against E. coli and S. aureus, respectively. Making coatings out of microspheres could effectively slow down the rotting and deterioration of cherry tomatoes during storage, suggesting that microspheres with intelligent responses have a broad application prospect in fruit preservation.

Photocatalytic degradation of p-nitrophenol using carbon microspheres loading Cu0 activation of peroxymonosulfate

Photocatalytic degradation of p-nitrophenol using carbon microspheres loading Cu0 activation of peroxymonosulfate

Relaxin-Loaded Inhaled Porous Microspheres Inhibit Idiopathic Pulmonary Fibrosis and Improve Pulmonary Function Post-Bleomycin Challenges.

Idiopathic pulmonary fibrosis (IPF) causes worsening pulmonary function, and no effective treatment for the disease etiology is available now. Recombinant Human Relaxin-2 (RLX), a peptide agent with anti-remodeling and anti-fibrotic effects, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, due to its short circulating half-life, optimal efficacy requires continuous infusion or repeated injections. Here, we developed the porous microspheres loading RLX (RLX@PMs) and evaluated their therapeutic potential on IPF by aerosol inhalation. RLX@PMs have a large geometric diameter as RLX reservoirs for a long-term drug release, but smaller aerodynamic diameter due to their porous structures, which were beneficial for higher deposition in the deeper lungs. The results showed a prolonged release over 24 days, and the released drug maintained its peptide structure and activity. RLX@PMs protected mice from excessive collagen deposition, architectural distortion, and decreased compliance after a single inhalation administration in the bleomycin-induced pulmonary fibrosis model. Moreover, RLX@PMs showed better safety than frequent gavage administration of pirfenidone. We also found RLX-ameliorated human myofibroblast-induced collagen gel contraction and suppressed macrophage polarization to the M2 type, which may be the reason for reversing fibrosis. Hence, RLX@PMs represent a novel strategy for the treatment of IPF and suggest clinical translational potential.

Polymer composite microspheres loading 177Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

BackgroundTransarterial radioembolization (TARE) with 90Y-labeled glass and resin microspheres is one of the primary treatment strategies for advanced-stage primary and metastatic hepatocellular carcinoma (HCC). However, difficulties of real-time monitoring post administration and embolic hypoxia influence treatment prognosis. In this study, we developed a new biodegradable polymer microsphere that can simultaneously load 177Lu and MgO nanoparticle, and evaluated the TARE therapeutic efficacy and biosafety of 177Lu-PDA-CS-MgO microspheres for HCC treatment.MethodsChitosan microspheres were synthesized through emulsification crosslink reaction and then conducted surface modification with polydopamine (PDA). The 177Lu and nano MgO were conjugated to microspheres using active chemical groups of PDA. The characteristics of radionuclide loading efficiency, biodegradability, blood compatibility, and anti-tumor effectwere evaluated both in vitro and in vivo. SPECT/CT imaging was performed to monitor bio-distribution and bio-stability of 177Lu-PDA-CS-MgO after TARE treatment. The survival duration of each rat was monitored. HE analysis, TUNEL analysis, immunohistochemical analysis, and western blot analysis were conducted to explore the anti-tumor effect and mechanism of composited microspheres. Body weight, liver function, blood routine examination were monitored at different time points to evaluate the bio-safety of microspheres.ResultsThe composite 177Lu-PDA-CS-MgO microsphere indicated satisfactory degradability, biocompatibility, radionuclide loading efficiency and radiochemical stability in vitro. Cellular evaluation showed that 177Lu-PDA-CS-MgO had significant anti-tumor effect and blocked tumor cell cycles in S phase. Surgical TARE treatment with 177Lu-PDA-CS-MgO significantly prolonged the medial survival time from 49 d to 105 d, and effectively inhibited primary tumor growth and small metastases spreading. Moreover, these microspheres indicated ideal in vivo stability and allowed real-time SPECT/CT monitoring for up to 8 weeks. Immunostaining and immunoblotting results also confirmed that 177Lu-PDA-CS-MgO had potential in suppressing tumor invasion and angiogenesis, and improved embolic hypoxia in HCC tissues. Further evaluations of body weight, blood test, and pathological analysis indicated good biosafety of 177Lu-PDA-CS-MgO microspheres in vivo.ConclusionOur study demonstrated that 177Lu-PDA-CS-MgO microsphere hold great potential as interventional brachytherapy candidate for HCC therapy.Graphical Polymer composite microspheres loading 177Lu radionuclide and MgO nanoparticles for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.

The Preparation and Characterization of Chitooligosaccharide–Polylactide Polymers, and In Vitro Release of Microspheres Loaded with Vancomycin

Drug-loaded microspheres are an ideal bone tissue delivery material. In this study, a biodegradable Schiff base chitosan–polylactide was used as the encapsulation material to prepare drug-loaded microspheres as biocompatible carriers for controlled vancomycin release. In this regard, Schiff base chitosan was prepared by the Schiff base method, and then different proportions of the Schiff base chitosan–polylactide polymer were prepared by ring-opening polymerization. Drug-loaded microspheres were prepared by the W/O emulsion method, and the polymers and polymer microspheres were characterized and studied by NMR, IR, and antibacterial methods. The drug loading and release rates of microspheres were determined to investigate the drug loading, encapsulation efficiency, and release rate of drug microspheres at different ratios. In this study, different proportions of Schiff base chitosan–polylactic acid materials are successfully prepared, and vancomycin-loaded microspheres are successfully prepared using them as carriers. This study proves that the materials have antibacterial activities against Staphylococcus aureus and Escherichia coli. The particle size of drug-loaded microspheres was below 10 μm, and the particle size decreased with decreasing molecular weight. The obtained results show that 1:100 microspheres have the highest drug-loading and encapsulation efficiencies, the drug-loaded microspheres have no burst release within 24 h, and the release quantity reaches more than 20%. After 30 days of release, the release amounts of 1:10, 1:20, 1:40, 1:60, and 1:100 drug-loaded microspheres were 64.80 ± 0.29%, 54.43 ± 0.54%, 44.60 ± 0.43%, 42.53 ± 0.40% and 69.73 ± 0.45%, respectively, and the release amount of 1:100 was the highest.

Hybrid hydrogel microspheres loading single-hole hollow imprinted particles for fast and selective uptake of 2′-deoxyadenosine

Hydrogel microspheres encapsulating molecularly imprinted polymers (MIPs) are promising hybrid sorbents, due to several advantages of high selectivity, fast mass transfer efficiency, and simple collection. Thus, Janus single-hole hollow nanoparticles (J-HNPs) with the size of 550 ± 70 nm were firstly designed by anisotropic emulsion template, and then MIPs were grafted onto their inner surface through electron transfer atom transfer radical polymerization (ARGET ATRP). Then as-prepared J-HNPs-MIPs were loaded into hydrogel microspheres via polymerizable water-in-oil (W/O) emulsion droplets combining gelatin methacryloyl (GMA) as monomers, and then obtained J-HNPs-MIPs@Gel with the mean diameter of 2.0 µm was applied for effective and selective separation of 2′-deoxyadenosine (dA). Fast adsorption equilibrium of J-HNPs-MIPs@Gel for dA can be achieved within 40 min, thanks to the hydrogel matrix and single-hole hollow structure for enhancing diffusion. The maximum multi-layer adsorption capacity calculated according to the Freundlich model was 10.31 μmol g−1 at 298 K. The specific memory to the size, shape and functional groups of dA endowed excellent recognition ability, and 88% of the initial capacity after four consecutive adsorption-desorption cycles was maintained. In addition, J-HNPs-MIPs@Gel was expected to show great potential for the selective enrichment and analysis of target dA molecule in complex biological samples.

Study on preparation and in vitro release of gelatin microspheres loaded with steroidal saponins from Ophiopogon japonicus

The purpose of this study is to develop microspheres (core/shell) based on natural polymers used for bone tissue engineering. The morphology, structure, particle size, drug loading and encapsulation efficiency of the microspheres were characterized by field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FTIR), ultraviolet spectrophotometer (UV) and laser particle size analyzer. The results showed that the gelatin (shell) microspheres loaded with steroidal saponins (core) prepared under the best process conditions were smooth and round, the particle size was about 4 μm. The drug loading and encapsulation efficiency were 24.7% and 97.5%, respectively. In the process of in vitro simulated release, the microspheres conformed to the first-order equation release kinetic model, and cumulative drug release in 8 days reached 85.6%. This may suggest the potential use of microspheres for treatment of bone tissue engineering over long periods.

Preparation of biocompatible wound dressings with dual release of antibiotic and platelet-rich plasma for enhancing infected wound healing.

The ever-growing threats of bacterial infection and chronic wound healing have provoked an urgent need for novel antibacterial wound dressings. In this study, we developed a wound dressing for the treatment of infected wounds, which can reduce the inflammatory period (through the use of gentamycin sulfate (GS)) and enhance the granulation stage (through the addition of platelet-rich plasma (PRP)). Herein, the sustained antimicrobial CMC/GMs@GS/PRP wound dressings were developed by using gelatin microspheres (GMs) loading GS and PRP, covalent bonding to carboxymethyl chitosan (CMC). The prepared dressings exhibited high water uptake capability, appropriate porosity, excellent mechanical properties, sustain release of PRP and GS. Meanwhile, the wound dressing showed good biocompatibility and excellent antibacterial ability against Gram-negative and Gram-positive bacteria. Moreover, in vivo experiments further demonstrated that the prepared dressings could accelerate the healing process of E. coli and S. aureus-infected full-thickness wounds in vivo, reepithelialization, collagen deposition and angiogenesis. In addition, the treatment of CMC/GMs@GS/PRP wound dressing could reduce bacterial count, inhibit pro-inflammatory factors (TNF-α, IL-1β and IL-6), and enhance anti-inflammatory factors (TGF-β1). The findings of this study suggested that biocompatible wound dressings with dual release of GS and PRP have great potential in the treatment of chronic and infected wounds.

Preparation of bacteriostatic microspheres loading potassium diformate using emulsification/external gelation

Potassium diformate (KDF) is a good substitute for antibiotics in animal feed. Based on the response surface methodology for optimizing the preparation conditions of microspheres. The optimal formulation was as follows: the concentration of ALG was 2 %, the concentration of CaCl2 was 2 %, and 0.4 mL of surfactant. The objective of the present study was to microencapsulate the KDF antibacterial microspheres by emulsification/external gelation. The structure, morphology and thermal properties of the obtained microspheres were characterized by XRD, SEM, FT-IR and TGA. Additionally, the encapsulation efficiency (EE%), loading capacity (LC%), antibacterial and slow-release properties of the prepared microparticles were evaluated. The results show that the optimized microspheres had spherical in morphology, in size, from 2 μm to 10 μm. Finally, the results of the in vitro antibacterial test showed that, when the concentration of antibacterial microspheres was 96 mg/mL, the antibacterial rates against Escherichia coli (E. coli) and Staphylococcus aureus were 89 % and 87 %, respectively, which effectively inhibited the excessive growth of the bacteria. The release kinetics model of the KDF microspheres in vitro revealed that the first-order release mechanism and Hixon-Crowell release mechanism were the primary release mechanisms, and the action time in the intestine could be delayed to 5 h.

Hybrid Hydrogel Microspheres Loading Single-Hole Hollow Imprinted Particles for Fast and Selective Uptake of 2'-Deoxyadenosine

Hybrid Hydrogel Microspheres Loading Single-Hole Hollow Imprinted Particles for Fast and Selective Uptake of 2'-Deoxyadenosine

Anti-inflammatory, Anxiolytic and Antioxidant Property of Lactuca sativa L and Formulation of Microspheres Loaded Sustained Release Anti-inflammatory Gel

Anti-inflammatory and anxiolytic properties of Lactuca sativa L extract was evaluated by formalin induced mice paw edema test, and elevated plus maze animal model respectively. Solid microspheres containing dispersed extract were obtained by water-in-oil-in-water multiple emulsion system followed by solvent evaporation method. Optimization was carried out using MINITAB 16 and optimized microspheres were loaded into a gel base. Anti-oxidant activity of optimized microspheres loaded gel was evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. The gel was also evaluated for its physical properties, drug release kinetics and anti-inflammatory activity using formalin induced mice-paw edema test where the anti-inflammatory potential was compared to marketed diclofenac gel (1.16% w/w). All doses of extract as well as microsphere loaded sustained release anti-inflammatory gel showed a dose and time dependent inhibition of edema (P<0.05), the extract also showed a dose dependent inhibition of level of anxiety (P<0.001). Potential anti-oxidant activity was seen with different concentration of crude extract and microsphere loaded gel. The anti-oxidant potential was compared using IC50 value which was 5.62 µg/mL, 6.34 µg/ml, 8.25 µg/mL for ascorbic acid, methanolic extract of L. sativa and microspheres loaded gel respectively.

Preparation and characterization of n-octylamine modified alginate/chitosan microspheres for controlled release of avermectin

Microspheres can be designed to increase the utilization of pesticides and reduce environmental pollution. In this study, the sodium alginate (SA) modified with n-octylamine was prepared, and the microspheres loading avermectin (AVM) were fabricated by orifice-coagulation bath using chitosan and modified/nature SA as the carrier materials. The particle size, granulation ratio, drug loading (DL) rate, embedding rate, swelling and sustained-release properties of microspheres were investigated. The Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were used to characterize the structure and morphology of microspheres. The results showed that the swelling and drug release properties of modified and unmodified microspheres showed good pH and thermo responsive. The DL performance of modified microspheres was improved, the embedding efficiency (EE) and DL were up to 60.3% and 75.8%, respectively. Furthermore, the AVM release time of microspheres with modified SA was prolonged and extended up to 48 h. All results indicated AVM of modified microspheres possessed higher utilization efficiency compared to the unmodified microspheres.

Antibiotic-loaded chitosan-gelatin scaffolds for infected seawater immersion wound healing

Skin damaged during sea battles is vulnerable to seawater immersion and bacterial infection. Scaffolds with effective biological function are highly desired for treatment of naval combat wound injuries. Herein, we prepared composite scaffolds of CS/GEL/GMs-CIP. The chitosan (CS) and gelatin (GEL) were cross-linked by genipin as matrix, and then gelatin microspheres loading ciprofloxacin hydrochloride (GMs-CIP) were add. From in vitro characterization results, CS/GEL/GMs-CIP had high water absorption ability, proper porosity, satisfactory fracture resistance, and flexibility. Furthermore, CS/GEL/GMs-CIP composite scaffold had excellent biocompatibility. Antibacterial experiments confirmed that CS/GEL/GMs-CIP had a significant inhibitory effect on E. coli, S. aureus and P. aeruginosa. The in vivo wound healing was evaluated using animal wound infection model of seawater immersion, and it was observed that the prepared composite scaffolds accelerated wound healing, reepithelialization, collagen deposition. Further analysis of wound tissue indicated that the expression of anti-inflammatory factor (TGF-β1) was up-regulated, but the serum endotoxin levels and expression of pro-inflammatory factor (TNF-a, IL-6, and IL-1β) were down-regulated. In summary, we believe that CS/GEL/GMs-CIP composite scaffold may serve as a promising multifunctional dressing for healing with open trauma wound infections and wound with seawater immersion.

Covalently injectable chitosan/chondroitin sulfate hydrogel integrated gelatin/heparin microspheres for soft tissue engineering

Microspheres and injectable hydrogels derived from natural biopolymers have been extensively investigated as drug carriers and cell scaffolds. In this study, we report a preparation of composite scaffolds basing microspheres and hydrogel via the Schiff’s base reaction. Hybrid gelatin/heparin microspheres loading insulin-like growth factor-1 (IGF-1) with a diameter of 5–10 µm were fabricated using an emulsion cross-linking method. Synchronously, water-soluble carboxymethyl chitosan (CMC) and oxidized chondroitin sulfate (OCS) were prepared for cross-linking of hydrogels, which were embedded with microspheres to produce a composite microspheres/gel scaffold. The mechanism of scaffold cross-linking is attributed to the Schiff’s base reaction between amino and aldehyde groups of biopolymers. Currently, gelation rate, morphology, mechanical properties, swelling ratio, weight loss, and IGF-1 release of the composite scaffolds were examined in vitro. The results show that mechanical and bioactive properties of CMC-OCS hydrogel can be significantly improved by embedding gelatin/heparin microspheres containing IGF-1. Compressive modulus of composite gel scaffolds containing 3 wt% of microspheres was 16 kPa, which was higher than the control hydrogel without microspheres. Cumulative release of IGF-1 during 7 days from microspheres embedded hydrogel was 70%, which was significantly lower than those of microspheres and hydrogels. Moreover, the composite microspheres/gel scaffolds exhibited higher swelling ratio and slower degradation rate than the control. Potential of the composite scaffolds was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) in vitro. Cell culture showed that this composite hydrogel could support survival and proliferation of ASCs. These results demonstrate the potential of gelatin/heparin microspheres embedded CMC-OCS hydrogels as an injectable scaffold in soft tissue engineering.

Novel triptorelin acetate-loaded microspheres prepared by a liquid/oil/oil method with high encapsulation efficiency and low initial burst release

Low encapsulation efficiency (EE) and high initial burst release are key issues for the development of microspheres loading highly water-soluble peptide drugs. In this study, novel triptorelin acetate-loaded microspheres with high EE and low initial burst release were prepared by a liquid/oil/oil (L/O/O) phase separation method using poly(lactic-co-glycolic acid) (PLGA) as the sustained-release carrier. The formulation of the microspheres and the preparation process were optimized in terms of particle size, surface morphology, EE, and in vitro drug release. Importantly, PLGA concentration, solvent and non-solvent ratio, solidification solvent volume, and solidification speed were found to significantly affect the properties of the obtained microspheres. The optimal microspheres present 50–100 μm spherical-shaped particles with remarkably high drug loading and EE. The in vitro drug release of these microspheres exhibit a delayed-release manner, starting to release drug at the third week and displaying approximately 20% drug release at day 28. Fourier transform infrared spectroscopy and differential scanning calorimetry results show that triptorelin acetate slightly interacted with PLGA, indicating that the drug was successfully encapsulated into PLGA microspheres. The drug content in the microspheres had no significant change after the 12-month storage at 4 °C, suggesting their excellent long-term stability. In conclusion, novel triptorelin acetate-loaded PLGA microspheres have been achieved via the L/O/O phase separation method to effectively improve the EE and reduce the initial burst release.

Evaluation of novel magnetic targeting microspheres loading adriamycin based on carboxymethyl chitosan

Targeted drug delivery system delivers drug to diseased organ, tissue, or cells by utilizing some physical means and biological properties, such as pH gradients in the intestine, differences in capillary diameters, immune system, specific enzymatic degradation, receptor responses, and specific chemical environment at the site of the lesion. Combining two preparation techniques of magnetic microspheres and ion exchange, regarding the anticancer drug adriamycin (ADR) as a model drug, carboxymethyl chitosan (CMC) as carrier, and Fe3O4 ultrafine particles as magnetic material, novel drug-loaded magnetic microspheres-ADR loaded carboxymethyl chitosan magnetic microspheres (ADR-CMC-Mag-MS) were synthesized. In this study, cytotoxicity and in vivo pharmacokinetics of ADR-CMC-Mag-MS were evaluated. The 50% cell inhibiting concentration (IC50) value of ADR-CMC-Mag-MS was (0.051 ± 0.005) μg/mL. And the cytotoxicity against human hepatocellular (Hep3B) cells presented concentration dependence. The area under the curve (AUC) and the peak concentration (Cmax) of ADR-CMC-Mag-MS added magnetic field (mag field) were respectively (1061.68 ± 22.71) μg·min/mL and (6.18 ± 0.13) μg/mL, indicating that the prepared ADR-CMC-Mag-MS had good targeting ability. It was demonstrated that the novel microspheres could deliver the highly toxic anticancer drug to the target site, in order to maximize the drug efficacy and reduce the side effects under the action of the external magnetic field.

Preparation, In Vivo and In Vitro Release of Polyethylene Glycol Monomethyl Ether-Polymandelic Acid Microspheres Loaded Panax Notoginseng Saponins.

In order to enrich the types of Panax notoginseng saponins (PNS) sustained-release preparations and provide a new research idea for the research and development of traditional Chinese medicine sustained-release formulations, a series of Panax notoginseng saponins microspheres was prepared by a double emulsion method using a series of degradable amphiphilic macromolecule materials polyethylene glycol monomethyl ether-polymandelic acid (mPEG-PMA) as carrier. The structure and molecular weight of the series of mPEG-PMA were determined by nuclear magnetic resonance spectroscopy (1 HNMR) and gel chromatography (GPC). The results of the appearance, particle size, drug loading and encapsulation efficiency of the drug-loaded microspheres show that the mPEG10000-PMA (1:9) material is more suitable as a carrier for loading the total saponins of Panax notoginseng. The particle size was 2.51 ± 0.21 μm, the drug loading and encapsulation efficiency were 8.54 ± 0.16% and 47.25 ± 1.64%, respectively. The drug-loaded microspheres were used for in vitro release and degradation experiments to investigate the degradation and sustained release behaviour of the drug-loaded microspheres. The biocompatibility of the microspheres was studied by haemolytic, anticoagulant and cytotoxicity experiments. The pharmacological activity of the microspheres was studied by anti-inflammatory and anti-tumour experiments. The results showed that the drug-loaded microspheres could be released stably for about 12 days and degraded within 60 days. At the same time, the microspheres had good biocompatibility, anti-inflammatory and anti-tumour activities.

Fabrication of HPMC and Hibiscus esculentus (okra) gum based microspheres loaded with sulfasalazine and dexamethasone

The study was aimed to synthesize and characterize effective sustained release polymeric microspheres of sulfasalazine and dexamethasone by using okra gum and hydroxypropyl methylcellulose (HPMC). The solvent extraction technique was used to synthesize sulfasalazine and dexamethasone loaded okra gum/HPMC microspheres. Pods of Hibiscus esculentus was used to extract okra gum. FTIR, DSC and SEM studies were performed. Kinetic modeling were applied on dissolution release data to evaluate release pattern of drugs from prepared formulations. No interaction was observed between drug and polymers by FTIR study. Molecular dispersion of sulfasalazine and dexamethasone was observed by DSC studies. SEM analysis showed acceptable morphology of microsphere. Dissolution studies showed that drug release was retarded up to 8 h when Okra gum and HPMC were used in combination but contrarily, HPMC and Okra gum showed early release of drug when both were used alone. Okra gum/HPMC microspheres of sulfasalazine and dexamethasone were prepared triumphantly by solvent evaporation method. Recovery, entrapment effectiveness hydration and drug loading of microspheres, influenced by the concentrations of Okra gum/HPMC.

Association of PLGA Microspheres to Carrier Pellets by Fluid Bed Coating: A Novel Approach towards Improving the Flowability of Microparticles.

Micro- and nanoparticles have been vastly studied due to their biopharmaceutical advantages. However, these particles generally display very weak packing and poor mechanical properties. Hereby, a new methodology is proposed to associate poorly flowing particles to macrostructures targeting the improvement of flowability and redispersibility of the particles. Cecropia glaziovii-loaded PLGA microspheres (4.59 ± 0.04 μm) were associated with carrier pellets by film coating in a top-spray fluid bed equipment. Optimal conditions were determined employing a IV-Optimal factorial design and RGB image analysis as 1% (w/v) Kollicoat® Protect as coating polymer (2:1 weight ratio of coating suspension to carrier pellets), containing 5 mg/mL microspheres (loading of 28.07 ± 1.01 mg/g). The method led to an improvement of the overall flowability. No relevant molecular interactions between PLGA microspheres and polymers were found. Microspheres detached rapidly from the surface of the pellets, without agglomeration, when exposed to hydrodynamic forces. In vitro release profiles, prior to and after fluid bed coating, showed no relevant changes in drug release rate and extent. The methodology developed is suitable for further applications when an improvement on the flow properties and redispersibility of the product is desired. We showed an easy-to-implement methodology that can be executed without significant increase in costs.

In vitro and in vivo evaluation of curcumin loaded hollow microspheres prepared with ethyl cellulose and citric acid

Curcumin (CUR) demonstrates a variety of biological activities; however, the poor oral bioavailability limits its clinical application. The objective of this study was to develop and evaluate characteristics and bioavailability of hollow microspheres loading curcumin (CUR-HPs). CUR-HPs were prepared by solvent diffusion and evaporation method. The effect of viscosity of ethyl cellulose (EC), amount of EC, citric acid (CA) and CUR on physicochemical characteristics and in vitro release profile of CUR-HPs were evaluated. Scanning electron microscopy (SEM) showed microspheres had smooth surfaces with hollow structures. The yield of CUR-HPs was (96 ± 1.80) %. The floating rate at 24 h was (89.67 ± 4.91) % and the drug loading was (3.41 ± 0.21) %. Nearly 95% of CUR was released from the HPs at 24 h. In vitro release profiles of CUR-HPs fitted the Korsmeyer et al.'s equation and indicated that CUR was released through the combination of diffusion and erosion mechanisms. The bioavailability of CUR-HPs was 12-fold higher than that of CUR. The peak time was delayed for 7.5 h and peak concentration of CUR-HPs was 3.21 times than that of free CUR. The CUR-HPs might be a promising strategy to achieve sustained release and increase oral bioavailability of CUR.