Microcapsule Formulations Research Articles

Preparation and application of pyraclostrobin microcapsule formulations

In this paper, pyraclostrobin-loaded polyurea microcapsules were prepared through interfacial polymerization reaction between isocyanates and amines. The microcapsules had size distribution ranging from 0.815 μm to 8.674 μm, nearly spherical shapes, and excellent encapsulation efficiency (EE > 90%). The release of pyraclostrobin from microcapsules was controlled by diffusion and erosion. The results of acute toxicity to zebrafish, spreadability on rice blades, and control effect on rice blast showed that the microcapsule formulations had significantly decreased toxicity to zebrafish (lower by 8–9-fold than that of emulsifiable concentrate), high spreadability on rice leaves, and satisfactory control efficacy against rice panicle blast (85.03%). This novel microencapsulation technology helps promote the environmental safety and control efficacy of pyraclostrobin.

Using Modified Starch/Maltodextrin Microparticles for Enhancing the Shelf Life of Ascorbic Acid by the Spray‐Drying Method

Chayotextle (Sechiumedule Sw.) starch is modified by acid hydrolysis for 3 h (MChS‐3h) or 6 h (MChS‐6h) and blended with 50 or 25% gum Arabic (GA). MChS‐3h, MChS‐6h, MChs‐3h‐GA, MChS‐6h‐GA, and GA formulations are used for microencapsulation of ascorbic acid (AA) by the spray‐drying method. The particle size, surface AA%, AA% retention, AA stability, X‐ray diffraction, and morphology of the microcapsules are considered to characterize the different microcapsule formulations. The amylose content decreases with hydrolysis time. Microcapsules made with MChS‐6h and MChS‐6h‐GA (75:25) show reduced values of median diameter (D [v, 0.5]) compared with microcapsules made with MChS‐3h and MChS‐3h‐GA (75:25). The concentration of GA has a positive effect on the particle size of microcapsules, a characteristic that is also observed in microscopy images. The percentage of retained AA is slightly greater for microcapsules made with MChS‐6h and MChS‐6h‐GA. The surface AA% shows similar values for all of the microcapsule formulations. However, the stability of AA over 12 weeks of storage exhibits some differences among the examined microcapsule formulations. Microcapsules made with MChS‐3h and MChS‐3h‐GA show a lower percentage of AA loss than microcapsules made with MChS‐6h and MChS‐6h‐GA. X‐Ray diffraction (XRD) analysis shows that AA is dispersed at the molecular level in the MChS and GA matrices of microcapsules. These results indicate that hydrolysis time plays a central role in the retention percentage and stability of AA.

POTENTIAL ANTITUMOR ACTIVITY OF CURCUMIN WITH RETINYLESTER MICRO-CAPSULED FORMULA

Background: The Bioavailabilty, efficacy and disease resistance of chemotherapy are the limitations of cancer treatment. This study was designed to formulate a microcapsules containing curcumin and retinylester as core material and tested the anti-cancer activity against different cancer cell lines. 
 Materials and methods: This study involved the design and formulation of microcapsules containing curcumin and retinylester as (core materials) embedded in dextrin/gelatin as wall materials. It was examined by Fourier-transform infrared spectroscopy FTIR and tested against HeLa and HepG2 cancer cell lines. 
 Results: Analysis of microcapsule by FTIR showed the characteristic band (2000cm-1~ 3800cm-1) that is indicated mainly from OH-, – CH3 and double bond. These bond stretching showed spectral bands peak 2975cm-1and 2670cm-1, 2836cm-1 respectively. The anticancer activity of these microcapsules on HeLA and HepG2 showed inhibition percent 87% and 85% respectively and non-toxic effect on normal cells. 
 Conclusion: Micro capsulated form of curcumin-retinylester showed an efficient medicinal mixture displayed a significant effect to HeLa and HepG2 cells which is very promising effective in the treatment of cancer.

Chitosan-carboxymethylcellulose based microcapsules formulation for controlled release of active ingredients from cosmeto textile

Chitosan-based emulsions were prepared at pH from 4.0 to 6.0. The zeta potential and droplet size were monitored at different pH. Double emulsions (wateroil- water) were observed due to the stiff conformation of chitosan at pH 4.0. At pH 5.0, the emulsion droplets were the smallest (2.9 μm) of the experimental pH range. The emulsion droplets were well dispersed due to high surface charge of chitosan (for example, +50 mV at pH 5.5) in entire pH range. The emulsion was treated with carboxymethyl cellulose (CMC) for neutralizing the charged chitosan on the surface of emulsion droplets. Above 10×10−2 mg/ml of CMC, no change in zeta potential was observed indicating no more free chitosan existed after neutralization with CMC. The emulsion was then crosslinked with different amount of glutaraldehyde. Upon increasing the amount of glutaraldehyde, the amount of core content inside the microcapsule and encapsulation efficiency of shell materials decreased gradually. The Dynamic Scanning Calorimetry data confirmed no interaction between core and shell material in the microencapsulation process. The thermal degradation of the microcapsules was examined by thermogravimetric analysis and a gradual decrease in the degradation temperature upon increasing glutaraldehyde concentration was found. The tuning of CMC concentration can provide valuable information regarding stable emulsion and efficient microcapsule formulation via coacervation.

Optimization of microcapsules shell structure to preserve labile compounds: A comparison between microfluidics and conventional homogenization method

A new technique is presented to optimize the formulation of microcapsules loaded with labile compounds. Fish oil was loaded into the microcapsule core and protected with a shell composed of whey protein microgel/beet pectin complexes. The microcapsules were formed using two different methods: microfluidics and homogenization. The microcapsules were further classified into three sub-groups. The first group was the microcapsules cross-linked with laccase (MCL), the second group was the microcapsules cross-linked with divalent cationic CaCl2 salt (MCS), and the third group consisted of control microcapsules (CM), with no cross-linking. The microfluidics method enabled tracking of the effect of the shell cross-linking ability of laccase, or CaCl2, on microcapsules. It was demonstrated that MCL obtained by microfluidics are more physicochemically stable than those produced via a homogenizer. The effect of cross-linking agents on the microcapsules were more significant when the microcapsules were produced by microfluidics.

DEVELOPMENT AND EVALUATION OF ALBENDAZOLE MICROCAPSULE FOR COLONIC DRUG DELIVERY SYSTEM

Objective: Albendazole is a benzimidazole carbamate broad spectrum oral anthelmetic drug. It is poorly water soluble and it undergoes extensive metabolism in the intestine and liver. Objective of present study was to prepare and evaluate microcapsule of Albendazole for colonic delivery. Methods: Six batches of Albendazole microcapsules were prepared using different concentration of polymers like Eudragit RS-100, chitosan, HPMC by solvent evaporation method. The microcapsules were then evaluated for micromeritic properties, percentage yield, incorporation efficiency, drug content. In vitro dissolution profile of each formulation was determined by employing USP XXIII rotating basket method. Results: The drug content was found to be very high in all formulations, incorporation efficiency was found to be good in all formulations. Highest incorporation efficiency 96.48 % was found in batch of MC6. Maximum drug release was shown by microcapsules formulation of batch MC6 (90.18%) Conclusion: Study concludes that Albendazole microcapsules may prove to be potential candidate for safe and effective sustained drug delivery. Peer Review History: Received 2 April 2017; Revised 6 May; Accepted 10 May, Available online 15 May 2017 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 3.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Mohamed Salama, Modern University for Technology & Information, Egypt, salama47@yahoo.com Dr. Hasniza Zaman Huri, University of Malaya Medical Centre, Kuala Lumpur, hasnizazh@ummc.edu.my Similar Articles: COLON SPECIFIC DRUG DELIVERY SYSTEMS: CURRENT TRENDS AND APPROACHES FORMULATION AND EVALUATION OF COLON TARGETED MATRIX TABLETS CONTAINING EXTRACT OF SOLENOSTEMMA ARGEL (HARGEL)

Development of a Chlorantraniliprole Microcapsule Formulation with a High Loading Content and Controlled-Release Property

Microcapsule formulations have been widely developed and used in agriculture to improve pesticide utilization and reduce environmental pollution. However, commercial formulations of chlorantraniliprole (CAP) are only traditional formulations due to poor solubility of CAP in organic solvents. Here, adopting a solid in oil in water (S/O/W) double-emulsion method combined with premix membrane emulsion, we successfully constructed CAP microcapsule formulations with a high loading content. The microcapsule formulations with good light and thermal stability showed a significantly sustained release for a long period, which could be optimally regulated by tuning the surface porosity and size of the porous microcapsules. Bioassay studies showed that control efficacy of the porous microcapsule formulations against Plutella xylostella was superior to that of the commercial formulation. These results demonstrated that such a porous microcapsule delivery system should have great potential for further exploration as a commercial CAP formulation.

Mixed extracts of green tea and orange peel encapsulated and impregnated on black tea bag paper to be used as a functional drink

SummaryHerbal drinks have been considered among the known groups of functional drinks. The aim of this study was to encapsulate green tea and orange peel extracts using double emulsion followed by complex coacervation to be used in the preparation of a functional drink. All of the microcapsule formulations were spherically prepared without cracks in the walls and their sizes increased by decreasing the ratio of the core to the wall. Microcapsules under the best conditions of this study were used to coat the paper of a bag containing black tea. The results showed that theaflavin and its ratio to thearubigin as the quality indices for black tea have increased in comparison with the sample without encapsulation. This study resulted in the production of encapsulated mixed extracts of green tea and orange peel that can be used later for the preparation of a functional drink.

Development of a sustained-release microcapsule for delivery of metoprolol succinate.

Sustained-release (SR) formulations of metoprolol succinate (MS) may minimize fluctuations in plasma concentration and decrease the resulting adverse events. The aim of the present study was to optimize the loading capacity of microcapsules and the SR of MS. A uniform design method was applied to optimize the formulation of SR microcapsules, composed of ethyl cellulose and polyethylene glycol 6,000, in one step via emulsion-solvent diffusion. In vitro release was studied, and the in vivo bioavailability of MS following dosing with novel microcapsules was compared with a commercially available MS formulation in beagle dogs. The present methodology achieved an entrapment efficiency of 83.2%, with 96.1% of drug released in vitro in 18 h, and the release was close to linear over a 12-h period. Pharmacokinetic studies of MS microcapsules in beagle dogs demonstrated a superior SR profile compared with conventional SR tablets. MS microcapsules were developed with high encapsulation efficiency, which had desirable SR properties in vitro and in vivo.

Survival of probiotics in pea protein-alginate microcapsules with or without chitosan coating during storage and in a simulated gastrointestinal environment.

Pea protein-alginate microcapsules with or without a chitosan coating and containing Lactobacillus rhamnosus R0011 and L. helveticus R0052 were produced by extrusion and tested for survivability during storage and in an in vitro gastrointestinal environment. Both microcapsule formulations provided significant protection for cells incubated in synthetic stomach juice at 37°C for 2 h, followed by 3 h in simulated intestinal fluid, relative to non-encapsulated bacteria. However, evaluation of cell viability during 9 weeks of storage at room temperature revealed that chitosan coating significantly improved microcapsule performance compared to non-coated microcapsules. Refrigerated storage had no negative impact on the microcapsule protection ability of both types of microcapsules. Notably, chitosan-containing microcapsules showed much higher bacterial survival counts during challenge tests even after storage. Moreover, the addition of chitosan to the microcapsule formulation did not increase the microcapsule size.

Layer-by-layer assembled magnetic prednisolone microcapsules (MPC) for controlled and targeted drug release at rheumatoid arthritic joints

We report here in about the formulation and evaluation of Magnetic Prednisolone Microcapsules (MPC) developed in order to improve the therapeutic efficacy relatively at a low dose than the conventional dosage formulations by means of magnetic drug targeting and thus enhancing bioavailability at the arthritic joints. Prednisolone was loaded to poly (sodium 4-styrenesulfonate) (PSS) doped calcium carbonate microspheres confirmed by the decrease in surface area from 97.48m2/g to 12.05 of m2/g by BET analysis. Adsorption with oppositely charged polyelectrolytes incorporated with iron oxide nanoparticles was confirmed through zeta analysis. Removal of calcium carbonate core yielded MPC with particle size of ~3.48µm, zeta potential of +29.7mV was evaluated for its magnetic properties. Functional integrity of MPC was confirmed through FT-IR spectrum. Stability studies were performed at 25°C±65% relative humidity for 60 days showed no considerable changes. Further the encapsulation efficiency of 63%, loading capacity of 18.2% and drug release of 88.3% for 36h and its kinetics were also reported. The observed results justify the suitability of MPC for possible applications in the magnetic drug targeting for efficient therapy of rheumatoid arthritis.

Controlled-release of Bacillus thurigiensis formulations encapsulated in light-resistant colloidosomal microcapsules for the management of lepidopteran pests of Brassica crops.

Bacillus thuringiensis (B. t.) based formulations have been widely used to control lepidopteran pests in agriculture and forestry. One of their weaknesses is their short residual activity when sprayed in the field. Using Pickering emulsions, mixtures of spores and crystals from three B. t. serovars were successfully encapsulated in colloïdosomal microparticles (50 μm) using innocuous chemicals (acrylic particles, sunflower oil, iron oxide nanoparticles, ethanol and water). A pH trigger mechanism was incorporated within the particles so that B. t. release occurred only at pH > 8.5 which corresponds to the midgut pH of the target pests. Laboratory assays performed on Trichoplusia ni (T. ni) larvae demonstrated that the microencapsulation process did not impair B. t. bioactivity. The best formulations were field-tested on three key lepidopteran pests that attack Brassica crops, i.e., the imported cabbageworm, the cabbage looper and the diamondback moth. After 12 days, the mean number of larvae was significantly lower in microencapsulated formulations than in a commercial B. t. formulation, and the effect of microencapsulated formulations was comparable to a chemical pesticide (lambda-cyhalothrin). Therefore, colloïdosomal microcapsule formulations successfully extend the bioactivity of B. t. for the management of lepidopteran pests of Brassica crops.

MICROENCAPSULACIÓN DE UN HIDROLIZADO PROTEÍNICO DE FRIJOL BAYO(Phaseolus vulgaris) CON ACTIVIDAD INHIBITORIA SOBRE LA ENZIMACONVERTIDORA DE ANGIOTENSINA-I MEDIANTE LIOFILIZACI ́ON

The aim of this study was to obtain microcapsules of a bayo bean protein hydrolysate (BBPH) with antihypertensive activity using Eudragit® L 30 D-55 as wall material (EGLD) through freeze-drying processing. The BBPH was obtained using sequential pepsin-pancreatin enzymatic system. The ACE-I inhibitory activity was measured using tripeptide hippurylhistidyl leucine (HHL) as model peptide. Three microcapsule formulations were prepared containing BBPH and EGLD at ratios of 1:20, 1:4 and 1:1, respectively. The physicochemical characteristics of microcapsules were evaluated by optical (OM) and scanning electronic microscopy (SEM), confocal laser scanning microscopy (CLSM), dierential scanning calorimetry (DSC), X-ray diraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). ACE-I inhibitory activity of BBPH was IC50=0.42 mg/mL. All microcapsules showed irregular shapes. The BBPH was distributed homogeneously in all formulations. The DSC and XRD analysis revealed a uniform dispersion of the BBPH and partially crystalline structures of EGLD and BBPH. The FT-IR confirmed the chemical stability of BBPH in the microcapsules. In conclusion, the EGLD microcapsules containing BBPH were prepared successfully by freeze-drying processing.

Formulation and characterization of Turkish oregano microcapsules prepared by spray-drying technology

The aim of this study was optimization of spray-drying process conditions for microencapsulation of Turkish oregano extract. Different concentrations of maltodextrin and gum arabic as encapsulating agents (wall material) as well as influence of selected processing variables were evaluated. The optimal conditions were maintained on the basis of the load of main bioactive compounds – ursolic, rosmarinic acids and carvacrol – in prepared microparticles after comparison of all significant response variables using desirability function. Physicomechanical properties of powders such as flowability, wettability, solubility, moisture content as well as product yield, encapsulation efficiency (EE), density, morphology and size distribution of prepared microparticles have been determined. The results demonstrated that the optimal conditions for spray-drying mixture consisted of two parts of wall material solution and one part of ethanolic oregano extract when the feed flow rate was 40 mL/min and air inlet temperature –170 °C. Optimal concentration of wall materials in solution was 20% while the ratio of maltodextrin and gum arabic was 8.74:1.26.

Construction of a controlled-release delivery system for pesticides using biodegradable PLA-based microcapsules

Conventional pesticides usually need to be used in more than recommended dosages due to their loss and degradation, which results in a large waste of resources and serious environmental pollution. Encapsulation of pesticides in biodegradable carriers is a feasible approach to develop environment-friendly and efficient controlled-release delivery system. In this work, we fabricated three kinds of polylactic acid (PLA) carriers including microspheres, microcapsules, and porous microcapsules for controlled delivery of Lambda–Cyhalothrin (LC) via premix membrane emulsification (PME). The microcapsule delivery system had better water dispersion than the other two systems. Various microcapsules with a high LC contents as much as 40% and tunable sizes from 0.68 to 4.6μm were constructed by manipulating the process parameters. Compared with LC technical and commercial microcapsule formulation, the microcapsule systems showed a significantly sustained release of LC for a longer period. The LC release triggered by LC diffusion and matrix degradation could be optimally regulated by tuning LC contents and particle sizes of the microcapsules. This multi-regulated release capability is of great significance to achieve the precisely controlled release of pesticides. A preliminary bioassay against plutella xylostella revealed that 0.68μm LC-loaded microcapsules with good UV and thermal stability exhibited an activity similar to a commercial microcapsule formulation. These results demonstrated such an aqueous microcapsule delivery system had a great potential to be further explored for developing an effective and environmentally friendly pesticide-release formulation.

Characterization of microcapsulated β-carotene formed by complex coacervation using casein and gum tragacanth

Complex coacervation in casein/gum tragacanth (CAS/GT) mixtures was studied as a function of pH, initial protein to polysaccharide mixing ratio (Pr:Ps), total biopolymer concentration, core material load and ionic strength. This study is aimed at understanding how these parameters influence the coacervation kinetics, the coacervate yield, and entrapment efficiency. At a Pr:Ps=2:1, an optimum pH of complex coacervation was found 4.35, at which the intensity of electrostatic interaction was maximum. At these conditions, the phase separation occurred the fastest and the final coacervate yield and entrapment efficiency were the largest. Moreover, the developed β-carotene loaded microcapsules formulation was found to have particle size 159.71±2.16μm, coacervates yield 82.51±0.412%, entrapment efficiency 79.36±0.541%. Varying the Pr:Ps shifted the value of optimum pH. Electrostatic interaction and formation of coacervates was confirmed by Fourier Transform Infra Red (FTIR) spectra. Size and surface properties of coacervates were studied using Scanning Electron Microscopy (SEM). Entrapment of core material within the coacervates was confirmed by Confocal Laser Scanning Microscope (CLSM). The resultant formulation was evaluated for release study and antioxidant activity. Stability of encapsulated β-carotene was evaluated under three levels of temperature (5, 25 and 40°C) for 3 months. Encapsulation strongly increased the stability of micronutrients. Our results advocate potential of microcapsules as a novel carrier for the safeguard and sustained release of micronutrient.

Formulation Design, Optimization, Characterization and In Vivo Pharmacodynamic Study of Enteric coated Mucoadhesive Microcapsules of Esomeprazole Magnesium

Background: The aim of the present study was to design and characterize the enteric coated mucoadhesive microcapsules of esomeprazole magnesium by solvent evaporation technique using drug, ethylcellulose and mucoadhesive polymer of 1:1:1 ratio for improving the mean gastric residence time and oral bioavailability of the drug. Methods: Characterization of the mucoadhesive microcapsules through FT-IR, and DSC studies showed lack of any significant interactions among drug and polymers, followed by complete encapsulation of the drug in the prepared formulation. Scanning electron microscopy indicated spherical morphology of the prepared formulation with intact nature of the outer coat. Results: This system remains in close contact with the absorption tissue and the mucous membrane, releasing the drug at the action site leading to enhancement in the oral bioavailability due to avoidance of hepatic first-pass metabolism. Physiological variables (i.e., mucin turnover from the mucus layer) plays major role in the estimation of mucoadhesive strength of formulation, by mucin turnover ensures significant amount of soluble mucin available for interaction with mucoadhesive polymer. Conclusion: The selected optimum formulation (F3c) identified from the current studies protected rat stomach ulcer induced by ethanol vis-à-vis the aqueous solution of the drug owing to optimum mucoadhesion, swelling and sustain drug release characteristics by prolonging the duration of action of the drug. Stability studies as per the ICH guidelines showed no significant alteration in drug content and release characteristics indicating stable nature of the optimized microcapsule formulation. Keywords: Gastric resistance, in vitro release profile, in vitro wash-off test, in vivo anti-ulcer activity, swelling index.

Optimasi Formula Mikroenkapsulasi Ekstrak Rimpang Temulawak (Curcuma xanthorrhiza Roxb.) dengan Penyalut Berbasis Air

Java turmeric (Curcuma xanthorrhiza Roxb. ) is a native plant of Indonesia which has been proved as anti-inflamation, antioxidant, antimicrobial, antitumor, hepatoprotective and antihyperlipidemic agent. The bitter taste with pungent aroma of java turmeric, improper storage that decreasing essential oil and curcuminoid level can be prevented by coating java turmeric as microcapsule. Recently, many microcapsule formulation is made based on organic solvent which have high risk on toxicity and also flammable. The study aimed to produce microcapsule using water based coating material from mixture of tapioca starch and carboxymethylceIlulose (CMC). There are 3 formulas of coating material that were used in this study, with proportion (w/v) of tapioca starch and CMC in formula I (3% : 1 %), formula II (2% : 2 %), and formula III (1% : 3%). The results showed that microcapsule with coating material made from formula III was the best, regarding to the measurements of physical parameter (recovery, water content, absorption efficiency, flow rate and particle size) and chemical parameter (curcumin content) compared to formula I and II. The higher CMC concentration on coating material compotition, the better microcapsule will be produced.

The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan–hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP ‘guarding’ effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.

PH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin.

This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin–sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit® FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery.