Microsphere Delivery System Research Articles

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine‐tuning Release Profiles (Small 46/2024)

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine‐tuning Release Profiles (Small 46/2024)

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles.

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

Review: Application of Polysaccharide Polymer Combination in Microsphere Delivery System for Anti-Tuberculosis

Review: Application of Polysaccharide Polymer Combination in Microsphere Delivery System for Anti-Tuberculosis

Development of mucoadhesive microspheres for intranasal delivery of fluconazole as an alternative treatment of cryptococcal meningitis infection in patients with acquired immunodeficiency

Cryptococcal meningitis is a deadly disease with few treatment options. Its incidence is still high and closely linked to the HIV/AIDS epidemic. This study aimed to develop a mucoadhesive microsphere delivery system for fluconazole for the intranasal route. Microspheres of mucoadhesive fluconazole formulation variables such as different amounts of drug concentration and polymer concentration were prepared by a simple emulsion-crosslinking method.The prepared microspheres' surface was characterised by SEM (Scanning electron microscopy) and evaluated for particle size, entrapment efficiency, production yield, infrared spectroscopic study, in-vitro muco-adhesion, and in-vitro drug release. The results showed that formula 1 is the optimal mucoadhesive microsphere preparation, with a particle size of 56.375m, a spherical surface shape, an entrapment efficiency of 99.96%, and a greater mucoadhesive capability during 6-hour evaluation. Furthermore, wash-off examination revealed that the mucoadhesive ability of this delivery system has a long duration and may release the active material at the right time. The result of the researches suggesting that the formulation of mucoadhesive microspheres of fluconazole could be used to treat cryptococcal meningitis infection in HIV/AIDS patients.

Design, Development and Evaluation of Tetracycline Controlled Release Microspheres

Microsphere drug delivery methods have been used to boost efficacy, reduce toxicity, and improve patient compliance. Additional benefits of using microspheres to deliver medications include controlled drug release, improved bioavailability, and targeted drug delivery to the desired location. In order to achieve the required therapeutic effect, hydroxypropyl methyl cellulose K4M and sodium alginate are used as a polymer in microsphere delivery system and different concentration of aluminium chloride is used as cross linking agent. The advantage of microsphere formulations over traditional tablet or capsule formulations is that they increase the surface area exposed to the absorption site, boosting medication absorption and reducing drug dose frequency. Tetracycline is a broad-spectrum antibiotic that is frequently used to treat illnesses like pneumonia and respiratory tract infections. The encapsulation effectiveness, particle size, in -vitro release analysis and release kinetics of the microsphere formulations was assessed.

Inflammation‐Regulated Auto Aggregated Hydrogel Microspheres Via Anchoring Cartilage Deep Matrix for Genes Delivery

AbstractThe high density structure of cartilage matrix negative charge seriously hinders the penetration and enrichment of drugs/genes into cartilage tissue. In this study, hexachlorocyclotriphosphonitrile is used as the core to prepare self‐polymerized phosphorus dendrimers with inflammatory reaction through substitution and condensation reaction. The vector can achieve efficient penetration of the damaged articular cartilage (slightly acidic condition) and effective anchoring of cartilage matrix (normal physiological condition) through the size effect under inflammatory response. Meanwhile, as a gene “delivery library,” G1‐NC5.HCl@siRNA is gradually released with microspheres degrading; the long‐term silencing of specific genes is realized. Further, G1‐NC5.HCl@siRNA is loaded into the hydrogel microspheres by ionic bond coordination and microfluidic techniques to improve the residency effect of G1‐NC5.HCl@siRNA in the joint cavity. The results of cartilage in vitro and in vivo experiments show that the gene complex has a better penetration effect at pH = 6.6, and the cartilage penetration effect decreases at pH = 7.6, which can effectively anchor in the cartilage matrix site for continuous drug delivery. Further, the composite hydrogel microspheres significantly improve the degeneration of osteoarthritis (OA) cartilage and promote cartilage regeneration. Therefore, the self‐polymerized hydrogel microsphere delivery system with inflammatory response is a promising penetrant/anchoring carrier system for OA treatment.

Influence of Chitosan Concentration on Characteristic of Microspheres Delivery System Prepared from Eleutherine palmifolia (L.) Merr. Extract

Background: Eleutherine palmifolia (L.) Merr. (E.palmifolia) is a medicinal plant containing naphthoquinone, isoliquiritigenin, and oxyresveratrol compound. This study aims to formulate and characterize the E. palmifolia microspheres delivery system using chitosan variation as the polymer. Methods: The preparation method was the solvent evaporation method. The microspheres delivery system was performed by variation of chitosan concentration in each formulation 0.637% (F1), 1.275% (F2), and 1.912% (F3). The physical and chemical characterizations include Entrapment Efficiency (EE), yield percentage, particle size, particle morphology, FTIR analysis, X-Ray Diffraction (XRD) analysis, and Differential Thermal Analysis (DTA) had been evaluated. Results: The results showed that chitosan concentration variation affected the microsphere's physical and chemical characteristics. Variations in the concentration of chitosan polymer (0.637%, 1.275% and 1.912%) had an effect on the physical characteristics of the microspheres of the resulting Dayak onion bulb extract. The higher the concentration of chitosan used, the higher the entrapment efficiency and the yield yield will increase. Meanwhile, in observing the particle size, the higher the concentration of chitosan used, the smaller the particle size produced. The optimal concentration of chitosan as a polymer at concentration variations of 0.637%, 1.275% and 1.912% to provide good physical characteristics of the Dayak onion bulb extract microspheres was shown in formula 3 with a chitosan concentration of 1.912%. Conclusion: The better characteristic was obtained upon higher chitosan concentration. The best physical characteristics of E.palmifolia extract microspheres were obtained from chitosan concentration at 1.912% (F3).

PREPARATION AND EVALUATION OF ONCE-DAILY FLOATING GMO-ALGINATE MICROSPHERES CONTAINING FAMOTIDINE

Objective: In this work, a gastro-retentive floating microsphere delivery system composed of Drug/Glyceryl mono-oleate (GMO) embedded in a Ca-alginate gas-generated matrix was designed to improve the bioavailability of a slightly-soluble model drug Famotidine. Methods: The water/Oil emulsion method was used to prepare Famotidine floatable microspheres, and formulation variables such as Alginate: GMO ratio, gas-generated bicarbonates concentration, and loading drug concentration were investigated. Conventional techniques, including DSC, XRD and FTIR were performed to confirm Famotidine compatibility with GMO and Alginate polymers. Real-Time X-ray Radiography was used for in vivo imaging of Famotidine floatable microspheres using rabbits as an animal model. HPLC spectroscopic technique was used to determine Famotidine plasma concentration after oral administration of Alginate-GMO loaded microspheres. Results: Floating Famotidine Alginate-GMO microspheres (0.75:1:0.25) w/w/w showed a remarkable entrapment efficiency (>98%), good buoyancy (>84) and prolonged in vitro drug release properties (>24 hours). DSC, XRD, and FTIR techniques showed no evidence of interaction between Famotidine and Alginate or GMO. In vivo Imaging of Famotidine floatable microspheres showed that capsules containing Famotidine-Alginate microspheres were not detected after 3 h of administration, while capsules containing Famotidine-GMO-Alginate microspheres can be detected for more than 12 h, indicating superior gastric retention properties. The pharmacokinetic parameters were calculated for Famotidine: GMO-Alginate, and Famotidine: alginate and compared with the plain drug over 24 h period. Famotidine: GMO-Alginate microspheres exhibited controlled and prolonged absorption Tmax of 6.0 vs. 3.0 and 2.0 h; Cmax of 124.9±0.9 vs. 323.7±0.4and 458.6±0.5 ng/ml; AUC0-24 of 2153.025±6.7 vs. 1650.4±1.9 and 1110.725±2.1 ng/ml for Famotidine: alginate and plain drug, respectively, reflecting the increase in the bioavailability of the drug in the floating formulations compared to the free drug. Conclusion: Prolonged gastric retention time and sustained release properties of floating GMO-alginate microsphere suggest that it could provide a valuable sustained release dosage form of slightly-soluble drugs.

New Hope for Treating Intervertebral Disc Degeneration: Microsphere-Based Delivery System.

Intervertebral disc (IVD) degeneration (IVDD) has been considered the dominant factor in low back pain (LBP), and its etiological mechanisms are complex and not yet fully elucidated. To date, the treatment of IVDD has mainly focused on relieving clinical symptoms and cannot fundamentally solve the problem. Recently, a novel microsphere-based therapeutic strategy has held promise for IVD regeneration and has yielded encouraging results with in vitro experiments and animal models. With excellent injectability, biocompatibility, and biodegradability, this microsphere carrier allows for targeted delivery and controlled release of drugs, gene regulatory sequences, and other bioactive substances and supports cell implantation and directed differentiation, aiming to improve the disease state of IVD at the source. This review discusses the possible mechanisms of IVDD and the limitations of current therapies, focusing on the application of microsphere delivery systems in IVDD, including targeted delivery of active substances and drugs, cellular therapy, and gene therapy, and attempts to provide a new understanding for the treatment of IVDD.

Dual sustained-release PTMC/PCL porous microspheres for lipid-soluble drugs

It is still a considerable research challenge to design biodegradable drug delivery systems that efficiently transport lipid-soluble drugs with controlled release. In the present study, a microsphere delivery system, γ-cyclodextrin (γ-CD)/glutathione (GSH)-atorvastatin (AT) fibrous nanoparticles (γ-CD/GSH-AT FNs) loaded polytrimethylene carbonate (PTMC)/polycaprolactone (PCL) microspheres (PTMC/PCL/γ-CD/GSH-AT MPs), was constructed through an exquisite method. The results show that a large number of γ-CD/GSH-AT FNs can be encapsulated during the formation of microspheres and released in a controllable manner. Notably, the high dispersibility and drug loading of FNs can load with lipid-soluble drugs and protect the drugs from the solvent during microsphere preparation. FNs and MPs can achieve dual release. First, with the degradation of the microspheres, the encapsulated FNs were gradually released into the local microenvironment. Subsequently, the FNs began to dissolve and release the loaded AT over a period of more than 3 days. Therefore, the dual sustained-release drug delivery system can maintain the blood drug concentration for a longer time and reduce the number of administrations and the side effects of the drug. This study provides new ideas for the on-demand manufacture of controllable degradable drug delivery platforms to treat diseases.

Development and Evaluation of Artemether-loaded Microspheres Delivery System for Oral Application in Malaria Treatment

a peer-reviewed, open access online international journal which publishes original research papers. The journal welcomes submission from scholars and experts for possible publication from all over the world. The scope of the journal includes: Pharmaceutical research, chemistry and biochemistry of naturally occurring compounds, biological evaluation of crude extracts, ethnomedicine, traditional and complementary medicine, ethnopharmacology, biomedical research, Biotechnology, Evaluation of natural substances of land and sea and of plants, microbes and animals, pharmacognosy, bioavailability, clinical, pharmacological, toxicological studies and pharmacokinetics of phytochemicals, Isolation and characterization of compounds, structure elucidation, synthesis and experimental biosynthesis of natural Product as well as developments of methods in these areas are welcomed in the journal.

Novel optimized drug delivery systems for enhancing spinal cord injury repair in rats

Effective and accurate delivery of drugs to tissue with spinal cord injury (SCI) is the key to rehabilitating neurological deficits. Sustained-release microspheres (MS) have excellent degradability and can aid in the long-term release of drugs. However, the burst release phenomenon can cause unexpected side effects. Herein, we developed and optimized an injectable poly(lactic-co-glycolic acid) (PLGA) MS loaded with melatonin(Mel), which were mixed further with Laponite hydrogels (Lap/MS@Mel, a micro-gel compound) in order to reduce the burst release of MS. Thus, these MS were able to achieve stable and prolonged Mel release, as well as synergistic Lap hydrogel in order to repair neural function in SCI by in situ injection. In clinical practice, patients with SCI have complicated conditions and significant inter-individual differences, which means that a single route of administration does not meet actual clinical needs. Thus, the nanospheres are synthesized and subsequently coated with platelet membrane (PM) in order to form PM/MS@Mel (nano-PM compound) for sustained and precision-targeted delivery of Mel intravenously in the SCI. Notably, optimized microsphere delivery systems have improved Mel regulation polarization of spinal microglial/macrophages, which can reduce loss of biomaterials due to macrophage-induced immune response during implantation of spinal cord tissue. These two new delivery systems that are based on MS provide references for the clinical treatment of SCI, according to different requirements.

Effect of inner pH on peptide acylation within PLGA microspheres

Polymer degradation within the controlled-release depots comprising of lactide and glycolide (PLGA) forms an acidic microenvironment, in which severe acylation of the peptide by the polymer degradation products takes place. The aim of this study was to make out the role of the inner μpH on peptide acylation within the microspheres and how could it influence the reaction. The effects of pH on the acylation reaction within microspheres were composed of two aspects. Firstly, the inherent effect of pH on the acylation reaction itself was figured out: with the pH environment going up from acid to neutral, a model peptide (octreotide acetate) acylation became more and more serious. Then, the multivariate effect of pH on the dynamic microsphere delivery system especially the state of the acylation substrates (drug and oligomer) was investigated. When the inner pH was neutralized by Ca(OH)2 to varying degrees, polymer degradation rate, drug release rate, polymer degradation mechanism and oligomer accumulation state within the microspheres all changed. These changes highly affected the mass transfer of the acylation substrates to the external release medium. Neutralization of the μpH prolonged the retention time of drug and oligomer within the microspheres. Water absorption and single microsphere swelling experiments all showed a higher retention amount of acylation substrates during the critical period for peptide acylation. Generally, when the inner μpH was neutralized, except that the neutral environment itself promoted acylation reaction, the effects of pH on the dynamic system were also highly responsible for the serious acylation within the microspheres.

Effect of recombinant human bone morphogenetic protein delivered by chitosan microspheres on ectopic osteogenesis in rats.

In the present study, the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered by chitosan (CS) microspheres on ectopic osteogenesis was investigated in a rat model. rhBMP-2-loaded CS microspheres and blank CS microspheres were prepared. A total of 24 male Sprague Dawley rats were divided into 4 groups with 6 rats in each group: The CS/rhBMP-2 group, the rhBMP-2 group, in which rhBMP-2 was directly implanted (rhBMP-2 dose in either group, 1 mg), the CS blank group and the control group. X-ray was performed at 4 weeks after ectopic osteogenesis surgery and micro-computed tomography (CT) examination was scheduled at 1, 2, 3 and 4 weeks after the surgery to determine ectopic osteogenesis in the different groups. Histological analysis, and determination of alkaline phosphatase (ALP) activity and calcium content were also performed. The mean diameter of the osteoid tissues was 1.1±0.3 cm (range, 0.8–1.4 cm) in the CS/rhBMP-2 group, which was significantly bigger than that in the rhBMP-2 group (0.3±0.1 cm; range, 0.1–0.4 cm) at 4 weeks after the surgery. X-ray analysis and micro-CT scan indicated that the area of high-density tissues and the radionuclide intensity, as well as bone volume in the 3-dimensional reconstruction were greatest in the CS/rhBMP-2 group, followed by those in the rhBMP-2 group. All parameters, including bone mineral density, tissue mineral density, tissue mineral content and bone volume fraction, were significantly higher in the CS/rhBMP-2 group at 3 and 4 weeks after the surgery, compared with those in the rhBMP-2 group. The histological analysis, ALP activity analysis and determination of calcium content revealed that the CS/rhBMP-2 system had the greatest ability to induce osteoblast differentiation. In conclusion, the CS/rhBMP-2 microsphere delivery system significantly enhanced the induction and promotion effects of rhBMP-2 regarding ectopic osteogenesis. The present study enhances the basic data available for future application of the CS/rhBMP-2 microspheres delivery system and provides a deeper understanding of the role of BMP-2 in bone regeneration.

Design, optimization and characterization of glutathione loaded-alginate microspheres for topical antiaging

Context: Glutathione in the reduced form (GSH) is the predominant intracellular form, which acts as a strong antioxidant. However, it has low skin permeability due to the high hydrophilicity. Hence, the objective of this study was to prepare GSH by using microspheres delivery system and adding surfactant to overcome the barrier function of the skin. Aims: To investigate the effect of polymer and surfactant on the characteristics and release profile of GSH–alginate microspheres. Methods: GSH-alginate microspheres were prepared using ionotropic gelation method by aerosolisation. A randomized full factorial design was applied to prepare four different formulations of glutathione loaded alginate microspheres. Design was applied for all formulations to study about effect of independent variables of polymer and crosslinker on the entrapment efficiency (EE), drug loading (DL), particle size, yield, and in vitro drug release profile. For release study, microspheres formulas were also compared to microspheres, which applied into gel base. Results: The GSH-alginate microspheres had a high EE ranging from 34.74 ± 0.07% to 56.63 ± 0.36%, with small particle sizes ranging from 1.89 ± 0.03 µm to 2.42 ± 0.08 µm, and drug loading ranging from 5.72 ± 0.05% to 6.23 ± 0.02%. The kinetic analysis of all release profiles was found to follow Higuchi’s diffusion model. EE, DL, particle size, and yield variables had a significant effect on the dependent variables (p<0.05), and flux had no significant effect on the dependent variables (p>0.05). Conclusions: All formulas produced high yield and encapsulation efficiency and small size particles. From the 22 randomized full factorial design, there was showed that the combination of the use of surfactant and polymer concentration significantly affected DL and EE.

Stereoselectivity evaluation of chiral chitosan microspheres delivery system containing rac-KET in vitro and in vivo

The influence of chiral excipient D-chitosan (CS) on the stereoselective release of racemic ketoprofen (rac-KET) microspheres has been investigated in comparison to those microspheres containing individual enantiomers in vitro and in vivo. Stereoselectivity was observed in vitro release test, with R-KET release slightly higher than that of S-KET, especially in 3% rac-KET loading microspheres. Stereoselectivity is dependent on the content of chiral excipient and pH of release medium. A molecular docking study between CS and KET enantiomers further revealed that S-KET has a stronger interaction with CS compared to R-KET. Moreover, the plasma concentration of KET enantiomers in rats shows substantial differences, as the plasma levels of S-KET were higher than those of R-KET. Plasma levels of enantiomers from the R-KET microspheres had similar stereoselectivity as rac-KET microspheres. The S/R ratio of rac-KET microspheres was significantly lower than that of rac-KET suspension (regular-release formulation) (p<.05), and the differences is 3–5 fold. Besides, rates of R-KET converted to S-KET exhibited differences between rac-KET microspheres and suspension. Similar results were also found between R-KET microspheres and suspension. All investigations suggest that the chitosan interacting preferentially with S-KET to R-KET significantly affect the stereoselective pharmacokinetics of rac-KET from chitosan microspheres in rats.

Compound pesticide controlled release system based on the mixture of poly(butylene succinate) and PLA

Controlled release system has been widely developed and utilised in agriculture to optimise efficacy and minimise environmental pollution. Here, the azoxystrobin and difenoconazole compound pesticide microsphere was constructed by the solvent evaporation method. Blending poly (butylene succinate) (PBS) and poly (lactic acid) (PLA) as shells, in order to increase its entrapment efficiency and match the goal of complex synergism. The resulting microsphere processes high entrapment efficiency with a mean diameter of 7.2 μm. Acute toxicity suggested microsphere on zebrafish was moderate toxicity. Comparative studies revealed that the microsphere had a longer period of sustained release than difenoconazole–azoxystrobin (5:8) 32.5% w/v suspension concentrate (SC). In addition, the concentration ratio of active ingredients closed to the optimum compound stoichiometry, which can achieve the objective of improving the efficacy of the pesticides. These results demonstrated that such a compound pesticide microsphere delivery system may be a considerable potential for further exploration.

Precisely controlled delivery of magnesium ions thru sponge-like monodisperse PLGA/nano-MgO-alginate core-shell microsphere device to enable in-situ bone regeneration

A range of magnesium ions (Mg2+) used has demonstrated osteogenic tendency in vitro. Hence, we propose to actualize this concept by designing a new system to precisely control the Mg2+ delivery at a particular concentration in vivo in order to effectively stimulate in-situ bone regeneration. To achieve this objective, a monodisperse core-shell microsphere delivery system comprising of poly (lactic-co-glycolic acid) (PLGA) biopolymer, alginate hydrogel, and magnesium oxide nano-particles has been designed by using customized microfluidic capillary device. The PLGA-MgO sponge-like spherical core works as a reservoir of Mg2+ while the alginate shell serves as physical barrier to control the outflow of Mg2+ at ∼50 ppm accurately for 2 weeks via its adjustable surface micro-porous network. With the aid of controlled release of Mg2+, the new core-shell microsphere system can effectively enhance osteoblastic activity in vitro and stimulate in-situ bone regeneration in vivo in terms of total bone volume, bone mineral density (BMD), and trabecular thickness after operation. Interestingly, the Young's moduli of formed bone on the core-shell microsphere group have been restored to ∼96% of that of the surrounding matured bone. These findings indicate that the concept of precisely controlled release of Mg2+ may potentially apply for in-situ bone regeneration clinically.

Efficient delivery of recombinant human bone morphogenetic protein (rhBMP-2) with dextran sulfate-chitosan microspheres.

Bone morphogenetic protein-2 (BMP-2) serves an important role in the development of bone and cartilage. However, administration of BMP-2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP-2 by carriers has been proven necessary to improve the osteogenesis effect of BMP-2. The present study constructed a novel drug delivery system using dextran sulfate (DS)-chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP-2). The microsphere morphology, optimal ratio of DS/CS/rhBMP-2, and drug loading rate and entrapment efficiency of rhBMP-2 CS nanoparticles were determined. L929 cells were used to evaluate the cytotoxicity and effect of DS/CS/rhBMP-2 microspheres on cell proliferation. Differentiation study was conducted using bone marrow mesenchymal stem cells (BMSCs-C57) cells treated with DS/CS/rhBMP-2 microspheres or the control microspheres. The DS/CS/rhBMP-2 microspheres delivery system was successfully established. Subsequent complexation of rhBMP-2-bound DS with polycations afforded well defined microspheres with a diameter of ~250 nm. High protein entrapment efficiency (85.6%) and loading ratio (47.245) µg/mg were achieved. Release of rhBMP-2 from resultant microspheres persisted for over 20 days as determined by ELISA assay. The bioactivity of rhBMP-2 encapsulated in the CS/DS microsphere was observed to be well preserved as evidenced by the alkaline phosphatase activity assay and calcium nodule formation of BMSCs-C57 incubated with rhBMP-2-loaded microspheres. The results demonstrated that microspheres based on CS-DS polyion complexes were a highly efficient vehicle for delivery of rhBMP-2 protein. The present study may provide novel orientation for bone tissue engineering for repairing and regenerating bone defects.

Reconstruction of Large-scale Defects with a Novel Hybrid Scaffold Made from Poly(L-lactic acid)/Nanohydroxyapatite/Alendronate-loaded Chitosan Microsphere: in vitro and in vivo Studies

A chitosan-based microsphere delivery system has been fabricated for controlled release of alendronate (AL). The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. The characteristics of CM-ALs scaffolds containing 10% and 20% CH/nHA-AL were evaluated in vitro, including surface morphology and porosity, mechanical properties, drug release, degradation, and osteogenic differentiation. The in vivo bone repair for large segmental radius defects (1.5 cm) in a rabbit model was evaluated by radiography and histology. In vitro study showed more sustained drug release of CM-AL-containing scaffolds than these of CM/nHA-AL and PLLA/nHA/AL scaffolds, and the mechanical and degradation properties of CM-ALs (10%) scaffolds were comparable to that of PLLA/nHA control. The osteogenic differentiation of adipose-derived stem cells (ASCs) was significantly enhanced as indicated by increased alkaline phosphates (ALP) activity and calcium deposition. In vivo study further showed better performance of CM-ALs (10%) scaffolds with complete repair of large-sized bone defects within 8 weeks. A microspheres-scaffold-based release system containing AL-encapsulated chitosan microspheres was successfully fabricated in this study. Our results suggested the promising application of CM-ALs (10%) scaffolds for drug delivery and bone tissue engineering.