Combination of adsorption by porous CaCO3 microparticles and encapsulation by polyelectrolyte multilayer films for sustained drug delivery

Combination of adsorption by porous CaCO(3) microparticles and encapsulation by polyelectrolyte multilayers via the layer-by-layer (LbL) self-assembly was proposed for sustained drug release. Firstly, porous calcium carbonate microparticles with an average diameter of 5 microm were prepared for loading a model drug, ibuprofen (IBU). Adsorption of IBU into the pores was characterized by ultraviolet (UV), infrared (IR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) experiment and X-ray diffraction (XRD). The adsorbed IBU amount Gamma was 45.1mg/g for one-time adsorption and increased with increasing adsorption times. Finally, multilayer films of protamine sulfate (PRO) and sodium poly(styrene sulfonate) (PSS) were formed on the IBU-loaded CaCO(3) microparticles by the layer-by-layer self-assembly. Amorphous IBU loaded in the pores of the CaCO(3) microparticles had a rapider release in the gastric fluid and a slower release in the intestinal fluid, compared with the bare IBU crystals. Polyelectrolyte multilayers assembled on the drug-loaded particles by the LbL reduced the release rate in both fluids. In this work, polymer/inorganic hybrid core-shell microcapsules were fabricated for controlled release of poorly water-soluble drugs. The porous inorganic particles are useful to load drugs in amorphous state and the polyelectrolyte multilayer films coated on the particle assuage the initial burst release.     

Nanoporous multilayer poly(L-glutamic acid)/chitosan microcapsules for drug delivery

Nanoporous poly(L-glutamic acid)/chitosan (PLGA/CS) multilayer microcapsules were fabricated by layer-by-layer (LbL) assembly using the porous silica particles as sacrificial templates. The LbL assembled nanoporous PLGA/CS microcapsules were characterized by Zeta-potential analyzer, FTIR, TGA, SEM, TEM and CLSM. 5-Fluorouracil (5-FU) was chosen as model drug. The drug loading content of PLGA/CS microcapsules depends on loading time, loading temperature, pH value and NaCl concentration. High loading capacity of microcapsules can be achieved by simply adjusting pH value and salt concentration. Moreover, 5-Fu loaded microcapsules take on a sustained release behavior, especially in an acid solution, in contrast to burst release of bare 5-Fu. The kinetics of 5-Fu release from PLGA/CS microcapsules conforms to Korsmeyer-Peppas and Baker-Lonsdale models, the mechanism of which can be ascribed to priority of drug diffusion and subordination of polymer degradation. The MTT cytotoxicity assay in vitro reveals the satisfactory anticancer activity of the drug-loaded PLGA/CS microcapsules. Therefore, the novel nanoporous PLGA/CS microcapsules is expected to find application in drug delivery systems.     

Small-molecule release from poly(D,L-lactide)/poly(D,L-lactide-co-glycolide) composite microparticles

Addition of biodegradable polymer shells surrounding polymeric, drug-loaded microparticles offers the opportunity to control drug release rates. A novel fabrication method was used to produce microparticles with precise control of particle diameter and the thickness of the polymer shell. The effect of shell thickness on release of a model drug, piroxicam, has been clearly shown for 2- to 15-microm thick shells of poly(D,L-lactide) (PDLL) surrounding a poly(D,L-lactide-co-glycolide) (PLG) core and compared to pure PLG microspheres loaded with piroxicam. Furthermore, the core-shell microparticles are compared to microspheres containing blended polymers in the same mass ratios to demonstrate the importance of the core-shell morphology. Combining PDLL(PLG) microcapsules of different shell thicknesses allows nearly constant release rates to be attained for a period of 6 weeks.     

Formulation and cytotoxicity of doxorubicin loaded in self-assembled bio-polyelectrolyte microshells

A bio-polyelectrolyte microshell composed of alginate sodium (ALG) and chitosan (CHI) was fabricated by electrostatic layer-by-layer (LbL) self-assembly technique. The resulting ALG-CHI microshells were found to be able to effectively load anti-cancer drug doxorubicin (DOX) in the interior of the shells under modest conditions without addition of other reagents, as demonstrated by confocal laser scanning microscopy (CLSM). The mass of DOX loaded in one capsule of four alginate/chitosan layers (i.e. the volume V=2.5x10(-10) cm3) is calculated as ca. 1.4x10(-13) g, which corresponds to 1.5x10(8) DOX molecules. Also, the release of DOX in the shells is dependent on the number of assembled layers of the shells. Colorimetric XTT cell viability assay results showed that the DOX-loaded microshells at high concentrations tested could kill cancer cells more efficiently than free-DOX alone.     

Preparation, characterization and in vitro cytotoxicity of indomethacin-loaded PLLA/PLGA microparticles using supercritical CO(2) technique.

In this work, indomethacin-loaded poly(l-lactic acid)/poly(lactide-co-glycolide) (IDMC-PLLA/PLGA) microparticles were prepared using solution-enhanced dispersion by supercritical fluids (SEDS) technique in an effort to obtain alternative IDMC formulation for drug delivery system. Surface morphology, particle size and particle size distribution, drug encapsulation efficiency, drug release kinetics, in vitro cytotoxicity and the cellular uptake of drug-loaded microparticles were investigated. The drug-loaded microparticles exhibited sphere-like shape and small particle size with narrow particle size distribution. IDMC was amorphously dispersed within the PLLA/PLGA matrix after the SEDS process. In vitro release studies revealed that the drug-loaded microparticles substantially enhanced the dissolution rate of IDMC compared to the free IDMC, and demonstrated a biphasic drug release profile. In vitro cytotoxicity assays indicated that drug-loaded microparticles possessed longer sustained inhibition activity on proliferation of the non-small-cell lung cancer A549 cell lines than did free IDMC. Fluorescence microscopy and transmission electron microscopy identified the phagocytosis of drug-loaded microparticles into the A549 cells and characteristic morphology of cell apoptosis such as the nuclear aberrations, condensation of chromatin, and swelling damage in mitochondria. These results collectively suggested that IDMC-PLLA/PLGA microparticles prepared using SEDS would have potentials in anti-tumor applications as a controlled drug release dosage form without harmful organic solvent residue.     

Encapsulation of ketoprofen for controlled drug release.

Ketoprofen particles were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 6 microm drug microcrystals through layer-by-layer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin/PSS bilayers with corresponding capsule wall thicknesses ranging from 41 to 111 nm. The release of Ketoprofen from the coated microparticles was measured in aqueous solutions of pH 1.4, 4.1, and 7.4. The release rate has changed at these different pH values. At pH 7.4 the release rate of Ketoprofen from the encapsulated particles was less by 107 times compared to uncoated Ketoprofen. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug crystals.     

Hyperbranched Polymers as Drug Carriers: Microencapsulation and Release Kinetics

The aim of this work was to study the feasibility of hyperbranched polymers as drug carriers by employing different microparticle formation methods and the influence of loading methods on release kinetics. Commercially available hyperbranched polyester (Perstorp) and three polyesteramides (DSM) were loaded with the pharmaceutical acetaminophen. The gas antisolvent precipitation (GAS), the coacervation, and the particles from gas saturated solutions (PGSS) are among conventional processes that were used to prepare microparticles of drug-loaded hyperbranched polyesters for the first time. For preparing solid dispersions of drug-loaded hyperbranched polyesteramides the solvent method was applied. Infrared (IR) and differential thermal analysis (DTA) studies suggest that acetaminophen is partly dissolved in the polymer matrix and partly crystallized outside the polymer matrix. For acetaminophen-loaded polyesters prepared by the GAS method, the presence of free drugs is predominant when compared to microparticles prepared by the coacervation method. This event disappears for microparticles prepared by the PGSS method. Moreover, the release of drug from drug-loaded Bol-GAS is biphasic, where the initial burst (48%), indicating the presence of unincorporated drugs, is followed by a slow-release phase, suggesting the diffusion of drug through polymer matrices. The release of drugs from drug-loaded Bol-PGSS do not show this behavior since the drug is better dissolved or dispersed in polymer matrices. In the case of drug-loaded polyesteramides, coevaporates prepared from 3 hyperbranched structures (H1690, H1200, and H1500) using the solvent method result in different release kinetics. The hydrophobic characteristic of hyperbranched polyesteramide H1500 shows the biphasic release kinetic whereas the drug released from hydrophilic matrices H1690 and H1200 exhibits fast release comparable to that of pure drug.     

Hyperbranched polymers as drug carriers: microencapsulation and release kinetics

The aim of this work was to study the feasibility of hyperbranched polymers as drug carriers by employing different microparticle formation methods and the influence of loading methods on release kinetics. Commercially available hyperbranched polyester (Perstorp) and three polyesteramides (DSM) were loaded with the pharmaceutical acetaminophen. The gas antisolvent precipitation (GAS), the coacervation, and the particles from gas saturated solutions (PGSS) are among conventional processes that were used to prepare microparticles of drug-loaded hyperbranched polyesters for the first time. For preparing solid dispersions of drug-loaded hyperbranched polyesteramides the solvent method was applied. Infrared (IR) and differential thermal analysis (DTA) studies suggest that acetaminophen is partly dissolved in the polymer matrix and partly crystallized outside the polymer matrix. For acetaminophen-loaded polyesters prepared by the GAS method, the presence of free drugs is predominant when compared to microparticles prepared by the coacervation method. This event disappears for microparticles prepared by the PGSS method. Moreover, the release of drug from drug-loaded Bol-GAS is biphasic, where the initial burst (48%), indicating the presence of unincorporated drugs, is followed by a slow-release phase, suggesting the diffusion of drug through polymer matrices. The release of drugs from drug-loaded Bol-PGSS do not show this behavior since the drug is better dissolved or dispersed in polymer matrices. In the case of drug-loaded polyesteramides, coevaporates prepared from 3 hyperbranched structures (H1690, H1200, and H1500) using the solvent method result in different release kinetics. The hydrophobic characteristic of hyperbranched polyesteramide H1500 shows the biphasic release kinetic whereas the drug released from hydrophilic matrices H1690 and H1200 exhibits fast release comparable to that of pure drug.     

Preparation of preformed porous PLGA microparticles and antisense oligonucleotides loading

The objective of this study was to load preformed highly porous microparticles with drug. The microparticles were prepared by a modified multiple emulsion (w/o/w) solvent evaporation method with the addition of pore formers (NaCl into the internal aqueous phase or of glycerol monooleate to the poly(lactide-co-glycolide) (PLGA) polymer phase). The drug-free solidified microparticles were then washed with either water (for NaCl) or hexane (for glycerol monooleate) to extract the pore formers. The drug was then loaded into the preformed porous microparticles by incubation in aqueous drug solutions followed by air- or freeze-drying. The drug was strongly bound to the polymeric surface with air-dried microparticles. A biphasic drug release with an initial rapid release phase (burst effect) was followed by a slower release up to several weeks. The initial burst was dependent on the drug loading and could be significantly reduced by wet (non-aqueous) temperature curing.     

Reduction in burst release after coating poly(D,L-lactide-co-glycolide) (PLGA) microparticles with a drug-free PLGA layer

The high initial burst release of a highly water-soluble drug from poly (D,L-lactide-co-glycolide) (PLGA) microparticles prepared by the multiple emulsion (w/o/w) solvent extraction/evaporation method was reduced by coating with an additional polymeric PLGA layer. Coating with high encapsulation efficiency was performed by dispersing the core microparticles in peanut oil and subsequently in an organic polymer solution, followed by emulsification in the aqueous solution. Hardening of an additional polymeric layer occurred by oil/solvent extraction. Peanut oil was used to cover the surface of core microparticles and, therefore, reduced or prevented the rapid erosion of core microparticles surface. A low initial burst was obtained, accompanied by high encapsulation efficiency and continuous sustained release over several weeks. Reduction in burst release after coating was independent of the amount of oil. Either freshly prepared (wet) or dried (dry) core microparticles were used. A significant initial burst was reduced when ethyl acetate was used as a solvent instead of methylene chloride for polymer coating. Multiparticle encapsulation within the polymeric layer increased as the size of the core microparticles decreased (< 50 µm), resulting in lowest the initial burst. The initial burst could be controlled well by the coating level, which could be varied by varying the amount of polymer solution, used for coating.     

Fabrication of drug-loaded polymer microparticles with arbitrary geometries using a piezoelectric inkjet printing system

Carrier geometry is a key parameter of drug delivery systems and has significant impact on the drug release rate and interaction with cells and tissues. Here we present a piezoelectric inkjet printing system as a simple and convenient approach for fabrication of drug-loaded polymer microparticles with well-defined and controlled shapes. The physical properties of paclitaxel (PTX)-loaded poly(lactic-co-glycolic acid) (PLGA) inks, such as volatility, viscosity and surface tension, were optimized for piezoelectric inkjet printing, and PTX-loaded PLGA microparticles were fabricated with various geometries, such as circles, grids, honeycombs, and rings. The resulting microparticles with 10% (w/w) PTX exhibited a fairly homogeneous shape and size. The microparticle fabrication by piezoelectric inkjet printing was precise, reproducible, and highly favorable for mass production. The microparticles exhibited a biphasic release profile with an initial burst due to diffusion and a subsequent, slow second phase due to degradation of PLGA. The release rate was dependent on the geometry, mainly the surface area, with a descending rate order of honeycomb>grid, ring>circle. The PTX-loaded microparticles showed a comparable activity in inhibiting the growth of HeLa cells. Our results demonstrate that a piezoelectric inkjet printing system would provide a new approach for large-scale manufacturing of drug carriers with a desired geometry.     

Preparation and characterisation of multilayer films and microcapsules containing poly(N-isopropylacrylamide-co-sodium vinylsulphonate) and applicability on controlled release

The copolymers of N-isopropylacrylamide and sodium vinylsulphonate were synthesised by free radical polymerisation. The layer-by-layer self-assembly of the copolymers with poly(allylamine) hydrochloride was performed through assembling onto silicon wafer to form multilayer films and onto CaCO₃ microparticles doped with poly(styrene sulphonate) as well as deltamethrin microcrystals to form microcapsules. The multilayer films and microcapsules were characterised by atomic force microscopy, transmission electron microscopy and scanning electron microscopy. The release behaviour of deltamethrin in the microcapsules under different conditions was also investigated by high performance liquid chromatography. Results show that these deltamethrin microcapsules have good thermo-sensitive properties and deltamethrin release can be controlled via changing temperature or self-assembly layers.     

Microencapsulation of antibiotic rifampicin in poly(3-hydroxybutyrate-co-3-hydroxyvalerate)

The aim of this study was the preparation of microparticles containing rifampicin using a biodegradable polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) for oral administration produced by a bacteria. The poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microparticles with and without rifampicin were prepared by the emulsification and solvent evaporation method, in which chloroform and polyvinyl alcohol are used as the solvent and emulsifier, respectively. Microparticles were obtained within a size range of 20-60 μm by changing the initial poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polyvinyl alcohol and rifampicin concentrations. An encapsulation efficiency value of 14% was obtained. The optimized total yield of 60% of the poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/ rifampicin was obtained. A load of 0.035 mg/1 mg of PHBV was reached. Almost 90% of the drug loaded in the microparticles was released after 24 h. The size, encapsulation efficiency and ribampicin release of the microparticles varied as a function of the initial poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polyvinyl alcohol and rifampicin concentrations. It was demonstrated that the microencapsulated rifampicin, although was not totally available in the medium, exhibited a similar inhibition value as free rifampicin at 24 h of incubation with S. aureus. Cytotoxicity assays demonstrated a reduction of the toxicity when rifampicin was microencapsulated in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) while maintaining its antibacterial activity.     

超微粒制备系统制备利培酮长效注射微球

目的:制备利培酮长效注射微球并进行体外释药动力学考察。方法:选用聚乳酸-羟基乙酸共聚物[poly(D,L-lactic-co-glycolic acid),PLGA]为载体,采用新型超微粒制备系统制备利培酮PLGA微球。以转碟上聚合物析出量、丝状物的形成和微粒表面形态为考察指标单因素实验优化制备工艺参数及处方;观察微球表面形态,测定其粒径、包封率、考察其体外释药动力学。结果:20%和30%载药量的微球表面均光滑圆整,分散性好;其包封率分别为94.7%和93.94%,中值粒径分别为31.65和28.13μm;持续释药时间均可达16 d,释放数据用释放动力学方程拟合符合一级和Higuchi方程。20%载药量微球1 h释药率仅为4.2%,突释率低,且其释放速率和释放时间与市售利醅酮微球(恒德)快速释放期基本一致而无延滞期。结论:超微粒制备系统(UPPS)可单步骤制备长效微球,工艺稳定,简单可行,有望成为一种适合工业微球制备技术。UPPS制备的20%载药量微球可开发为释放2周的制剂,由于无释放延滞期,将比市售品更具临床优势。     

Production of pH-Responsive Microparticles by Spray Drying: Investigation of Experimental Parameter Effects on Morphological and Release Properties

During spray drying, emphasis is placed on process optimisation to generate favourable particle morphological and flow properties. The effect of the initial feed solution composition on the drug release from the prepared microparticles (MPs) is rarely considered. We investigated the effects of solvent composition, feed solution concentration and drug-loading on sodium salicylate, hydrocortisone and triamcinolone release from spray-dried Eudragit L100 MPs. Eudragit L100 is a pH-responsive polymer whose dissolution threshold is pH 6 so dissolution testing of the prepared MPs at pH 5 and 1.2 illustrated non-polymer controlled burst release. Increasing the water content of the initial ethanolic feed solution significantly reduced hydrocortisone burst release at pH 5, as did reducing the feed solution concentration. These findings caution that changes in feed solution concentration or solvent composition not only affect particles' morphological characteristics but can also negatively alter their drug release properties. This work also illustrate that drug-free MPs can have different morphological properties to drug-loaded MPs. Therefore, process optimisation needs to be carried out using drug-loaded systems. Depending on the physicochemical properties of the encapsulated active pharmaceutical ingredient (API), drug-loading can affect the polymer solubility in the initial feed solution with consequent impact on MPs morphological and release properties.     

Encapsulation of water-soluble drugs by an o/o/o-solvent extraction microencapsulation method

A new o/o/o-solvent extraction microencapsulation method based on less toxic solvents is presented in this study. The drug is dissolved/dispersed into a poly(D,L-lactide)/or poly (D,L-lactide-co-glycolide) (PLGA) solution in a water-miscible organic solvent (e.g., dimethylsulfoxide or 2-pyrrolidone) (o(1)), followed by emulsification into an oil phase (o(2)) (e.g., peanut oil). This emulsion is added to the external phase (o(3)) to solidify the drug-containing polymer droplets. The polymer solvent and the oil are extracted in an external phase (o(3)) (e.g., ethanol), which is a nonsolvent for the polymer and miscible with both the polymer solvent and the oil. One major advantage of this method is the reduced amount of solvent/nonsolvent volumes. In addition, very high encapsulation efficiencies were achieved at polymer concentration of 20%, w/w for all investigated polymers and o(1)/o(2) phase ratios with ethanol as the external (o(3)) phase. The encapsulation efficiency was very low (<20%) with water as external phase. The particle size of the microparticles increased with increasing polymer concentration and o(1)/o(2) phase ratio and larger microparticles were obtained with 2-pyrrolidone compared to dimethylsulfoxide as polymer solvent (o(1)). After an initial burst, in vitro drug release from the microparticles increased for the investigated polymer as follows: Resomer(?) RG 506>RG 756>R 206. A third more rapid release phase was observed after 6 weeks with Resomer(?) RG 506 due to polymer degradation. Similar drug release patterns were obtained with the o/o/o and w/o/w multiple emulsion methods because of similar porous structures. This new method has the advantages of less toxic solvents, much lower preparation volume and solvent consumption and high encapsulation efficiencies when compared to the classical w/o/w method.     

Effect of poly(lactide-co-glycolide) molecular weight on the release of dexamethasone sodium phosphate from microparticles

The objective of this study was to investigate the effect of poly(lactide-co-glycolide) (PLGA) molecular weight (Resomer RG 502H, RG 503H, and RG 504H) on the release behavior of dexamethasone sodium phosphate-loaded microparticles. The microparticles were prepared by three modifications of the solvent evaporation method (O/W-cosolvent, O/W-dispersion, and W/O/W-methods). The encapsulation efficiency of microparticles prepared by the cosolvent- and W/O/W-methods increased from approximately 50% to >90% upon addition of NaCl to the external aqueous phase, while the dispersion method resulted in lower encapsulation efficiencies. The release of dexamethasone sodium phosphate from PLGA microparticles (>50 microm) was biphasic. The initial burst release correlated well with the porosity of the microparticles, both of which increased with increasing polymer molecular weight (RG 504H > 503H > 502H). The burst was also dependent on the method of preparation and was in the order of dispersion method > WOW method > consolvent method. In contrast to the higher molecular weight PLGA microparticles, the release from RG 502H microparticles prepared by cosolvent method was not affected by volume of organic solvent (1.5-3.0 ml) and drug loading (4-13%). An initial burst of approximately 10% followed by a 5-week sustained release phase was obtained. Microparticles with a size <50 microm released in a triphasic manner; an initial burst was followed by a slow release phase and then by a second burst.     

Preparation of sustained release microparticles with improved initial release property

The objective of this study was to investigate the potential of various formulation strategies to achieve sustained release of the peptide, from injectable poly(D,L-lactide-co-glycolide) (PLGA) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) microparticles. The microparticles were prepared by a solvent evaporation method. Peptide loaded PLGA microparticles exhibited a pronounced initial burst release (22.3% in 1 day) and lag phase in phosphate buffer of pH 7.0. In contrast, blending of 5.0% TPGS (8.6% release in 1 day) or 10.0% TPGS (5.5% release in 1 day) in PLGA microparticles reduced initial burst release and the lag-phase time. Incorporation of TPGS in PLGA microparticles further increased drug release, attributable to improved drug encapsulation, increased particle size, and exempt of pores. PLGA+ 10.0% TPGS composite microparticles exhibited the most desirable drug release among all the formulations tested, and demonstrated triphasic release after minimal initial burst.     

A novel in situ forming drug delivery system for controlled parenteral drug delivery

The objective of this study was to investigate the in vitro drug (diltiazem hydrochloride and buserelin acetate) release from different in situ forming biodegradable drug delivery systems, namely polymer solutions (in situ implants) and in situ microparticle (ISM) systems. The drug release from ISM systems [poly(d,l-lactide) (PLA) or poly(d,l-lactide-co-glycolide) (PLGA)-solution dispersed into an external oil phase] was investigated as a function of the type of solvent and polymer, polymer concentration and internal polymer phase:external oil phase ratio and was compared to the drug release from in situ implant systems and microparticles prepared by conventional methods (solvent evaporation or film grinding). Upon contact with the release medium, the internal polymer phase of the ISM system solidified and formed microparticles. The initial drug release from ISM systems decreased with increasing polymer concentration and decreasing polymer phase:external oil phase ratio. The type of biocompatible solvent also affected the drug release. It decreased in the rank order DMSO>NMP>2-pyrrolidone. In contrast to the release of the low molecular weight diltiazem hydrochloride, the peptide release (buserelin acetate) was strongly dependent on the polymer degradation/erosion. One advantage of the ISM system when compared to in situ implant systems was the significantly reduced burst effect because of the presence of an external oil phase. ISM systems resulted in drug release profiles comparable to the drug release of microparticles prepared by the solvent evaporation method. Therefore, the ISM systems are an attractive alternative to existing complicated microencapsulation methods.     

In vitro and in vivo evaluation of anti-inflammatory agents using nanoengineered alginate carriers: towards localized implant inflammation suppression

The aim of this research was to develop nanoengineered alginate microspheres for localized delivery of anti-inflammatory drugs (dexamethasone and diclofenac sodium) for implantable "Smart tattoo" glucose biosensor used for continuous glucose monitoring. The formulation was prepared and characterized for in vitro drug release from uncoated and polyelectrolyte-coated microparticles. Biocompatibility was then tested using L929 cell-line; pilot in vivo studies with Sprague-Dawley (SD) rat subjects were performed to test the suppression of inflammation and fibrosis associated with implantation and was analyzed using standard hematoxylin and eosin staining method. The drug-loaded microspheres were able to deliver the drug for 30 days at a controlled rate with zero-order kinetics. The layer-by-layer self-assembly technique was used to effectively limit the burst release of drug from the matrix. Cell culture studies prove that the material are not cytotoxic and showed acceptable >80% cell viability in all the tested samples. In vivo studies show that both drugs were successful in controlling the implant/tissue interface by suppressing inflammation at the implant site. It was clearly evident that the combined approach of drug loaded carriers along with implanted biosensor shows promise in improving sensor biocompatibility and functionality. Thus, suggesting potential application of alginate microspheres as "smart-tattoo" glucose sensors.