Sodium Alginate Microparticles Research Articles

Formulation and Evaluation of Insulin-Loaded Sodium-Alginate Microparticles for Oral Administration.

The development of oral insulin drug delivery systems is still an ongoing challenge for pharmaceutical technology researchers, as the formulation process has to overcome a number of obstacles due to the adverse characteristics of peptides. The aim of this study was to formulate different sodium-alginate microparticles as a possible method for oral insulin administration. In our previous studies, the method has been successfully optimized using a small model peptide. The incorporation of insulin into alginate carriers containing nonionic surfactants has not been described yet. In order to enhance the absorption of insulin through biological barriers, Labrasol ALF and Labrafil M 2125 CS were selected as permeation-enhancing excipients. They were applied at a concentration of 0.10% (v/v%), along with various combinations of the two, to increase oral bioavailability. Encapsulation efficiency showed sufficient drug incorporation, as it resulted in over 80% in each composition. In vitro dissolution and enzymatic stability test results proved that, as a pH-responsive polymer, alginate bead swelling and drug release occur at higher pH, thus protecting insulin against the harsh environment of the gastrointestinal tract. The remaining insulin content was 66% due to SIF degradation after 120 min. Permeability experiments revealed the impact of permeation enhancers and natural polymers on drug absorption, as they enhanced drug transport significantly through Caco-2 cells in the case of alginate microparticle formulations, as opposed to the control insulin solution. These results suggest that these formulations are able to improve the oral bioavailability of insulin.

Alginate-Based Patch for Middle Ear Delivery of Probiotics: A Preliminary Study Using Electrospray and Electrospinning

Antimicrobial resistance poses a growing challenge in respiratory tract diseases like otitis media, often necessitating surgical interventions due to pharmacological treatment limitations. Bacteriotherapy, involving probiotics and/or their bioproducts, emerges as a promising alternative in such a scenario. This study aims to pave the way to middle ear bacteriotherapy by developing an innovative sodium alginate (SA)-based probiotic delivery system using electrospinning and electrospray techniques. Electrospray enabled the precise production of probiotic-laden SA microparticles, demonstrating potential for targeted bacterial delivery. By overcoming challenges due to the SA molecular structure, we successfully electrospun SA-based fiber meshes with poly(ethylene oxide) (PEO) as a support polymer. The rheologic behavior of the probiotic/SA solutions and the morphology of the obtained microparticles and fibers was evaluated, along with the diameter variation over time. The cytocompatibility of the produced microparticles and fibers was assessed using human dermal keratinocytes and their antimicrobial activity was tested against E. coli. The incorporation of probiotic-laden SA microparticles within electrospun SA/PEO fiber meshes finally offered a patch-like structure to be applied on the tympanic membrane or on the outer auditory canal, which could be a versatile and ideally safe treatment strategy in chronic otitis media. This innovative approach holds promise for clinical applications dealing with inflammatory processes, infections and dysbiosis, thus possibly addressing the complex healing process of chronic upper respiratory diseases while mitigating antimicrobial resistance.

Soy Protein Isolate/Sodium Alginate Microparticles under Different pH Conditions: Formation Mechanism and Physicochemical Properties

The effects of sodium alginate (SA) and pH value on the formation, structural properties, microscopic morphology, and physicochemical properties of soybean protein isolate (SPI)/SA microparticles were investigated. The results of ζ-potential and free sulfhydryl (SH) content showed electrostatic interactions between SPI and SA, which promoted the conversion of free SH into disulfide bonds within the protein. The surface hydrophobicity, fluorescence spectra, and Fourier transform infrared spectroscopy data suggested that the secondary structure and microenvironment of the internal hydrophobic groups of the protein in the SPI/SA microparticles were changed. Compared with SPI microparticles, the surface of SPI/SA microparticles was smoother, the degree of collapse was reduced, and the thermal stability was improved. In addition, under the condition of pH 9.0, the average particle size of SPI/SA microparticles was only 15.92 ± 0.66 μm, and the distribution was uniform. Rheological tests indicated that SA significantly increased the apparent viscosity of SPI/SA microparticles at pH 9.0. The maximum protein solubility (67.32%), foaming ability (91.53 ± 1.12%), and emulsion activity (200.29 ± 3.38 m2/g) of SPI/SA microparticles occurred at pH 9.0. The application of SPI/SA microparticles as ingredients in high-protein foods is expected to be of great significance in the food industry.

Cover Image, Volume 138, Issue 44

The cover image created by Zheng Zhao and his colleagues shows an SEM micrography of sodium alginate (SA)/silk fibroin (SF) composite scaffolds with extracellular matrix (ECM)-like nanofibrous structures developed by supercritical CO2 technology. And the SA microparticles are embedded in the SF scaffolds. Increasing the SA content can improve the mechanical properties of the SF scaffolds and reduce the porosity of the SF scaffolds. Moreover, the SA microparticles can regulate the degradation rate of the SA/SF composite scaffolds. In addition, the SA/SF composite scaffolds exhibit higher L929 fibroblasts attachment and proliferation ability than the SF scaffolds. DOI: 10.1002/app.51421

Supercritical carbon dioxide assisted fabrication of biomimetic sodium alginate/silk fibroin nanofibrous scaffolds

AbstractIn this study, biomimetic sodium alginate (SA)/silk fibroin (SF) scaffolds were successfully fabricated by supercritical CO2technology. The SA/SF scaffolds exhibited an interconnected porous and extracellular matrix (ECM)‐like nanofibrous structures. Moreover, the SA microparticles were embedded in the SF scaffolds. Increasing the content of SA microparticles could improve tensile strength and compressive strength of the SF scaffolds and reduce the porosity of the SF scaffolds. The addition of the SA microparticles could also regulate the degradation rate of the SA/SF scaffolds. Furthermore, the results of in vitro biocompatibility evaluation, indicated that the SA/SF scaffolds exhibited no obvious cytotoxicity and higher cell adhesion ability and were more favorable for L929 fibroblasts proliferation than pure SF scaffolds. Therefore, the SA/SF scaffolds with ECM‐like nanofibrous and interconnected porous structure have potential application in skin tissue engineering.

Three fluid nozzle spray drying for co-encapsulation and controlled release of curcumin and resveratrol

This study reports the first time development of sodium alginate and carboxy methyl cellulose microparticles for co-delivery of curcumin and resveratrol through conventional two fluid nozzle (2FN) and three fluid nozzle (3FN) spray drying. More than 9% increase in loading capacity and encapsulation efficiency of bioactives was observed in microparticles formed through 3FN than from 2FN spray drying. Florescence imaging proved the formation of core-shell microparticles from 3FN spray drying. DSC and XRD pattern confirmed that encapsulation changes the crystallinity of bioactives to amorphous form. Controlled release of resveratrol encapsulated in the core of the microparticles produced from 3FN was evident in comparison with 2FN microparticles. Release kinetics of both bioactives best fit the Korsmeyer-Peppas model, explaining pseudo-Fickian diffusion mechanism for resveratrol from core and anomalous diffusion for curcumin from shell. Overall, results confirmed that the 3FN spray drying is a prospective commercially scalable approach for effective co-delivery of bioactive molecules.

Preparation and Evaluation of Sodium Alginate Microparticles using Pepsin

Aim: The main aim of this article is to prepare and evaluate sodium alginate microparticles and evaluate on the basis of their characterization. The drug is dissolved, encapsulated or attached to a microparticles matrix. Depending upon method of preparation microparticles were obtained. Microparticles were developed as a carrier for vaccines and other disease like rheumatoid arthritis, cancer etc. Microparticles were developed to increase the efficacy of active pharmaceutical ingredient to a specific targeted site.
 Material and Method: Microparticles of Sodium Alginate, Pepsin and Calcium Chloride were prepared in six batches (A-F) with different ratio of sodium alginate and calcium chloride respectively i.e. (0.25:2.5), (0.25:5), (0.25:7.5), (0.5:2.5), (0.5:5), (0.5:7.5) by using a homogenizing method. Microparticles were evaluated for particle size distribution, zeta potential and morphology.
 Result and Discussion: The normal particle size of each of the six batches were analyzed by Zeta Sizer (Delsa C Particle Analyzer) and it was found that the Batch B (0.25:5) delivered the best microparticles with size distribution of 1.2731 (µm). All batches were seen under Motic magnifying microscope by using the Sulforhodamine B (M.W. 479.02) color as staining dye. Microparticles was found to be semi spherical in shape.
 Conclusion: Results of all the six batches was contrasted based on particle size investigation, zeta potential and morphology. Batch B (0.25:5) was considered as the best formulation.
 Key words: Micro Particle, Pepsin, Sodium Alginate and Calcium Chloride, Sulforhodamine B, Zeta Sizer.

Spray-dried alginate microparticles for potential intranasal delivery of ropinirole hydrochloride: development, characterization and histopathological evaluation

Ropinirole hydrochloride (RH) is an anti-Parkinson drug with relativity low oral bioavailability owing to its extensive hepatic first pass metabolism. Spray-dried mucoadhesive alginate microspheres of RH were developed and characterized followed by histopathological evaluation using nasal tissue isolated from sheep. Spherical microparticles having high product yield (around 70%) were obtained when the inlet temperature of spray drying was 140 °C. Fourier Transform Infrared (FTIR) studies revealed the compatibility of the drug with the polymer, and scanning electron microscopy (SEM) showed that drug-loaded microparticles were spherical, and the apparent surface roughness was inversely related to the ratio of polymer to drug. Furthermore, size of the spray-dried particles were in the range of 2.5–4.37 µm, depending on formulation. All formulations had high drug encapsulation efficiencies (101–106%). Drug loaded into the polymeric particles was in the amorphous state and drug molecules were molecularly dispersed in the polymeric matrix of the microparticles which were revealed by X-ray diffraction and differential scanning calorimetry (DSC), respectively. The in vitro drug release was influenced by polymer concentration. Histopathological study demonstrated that RH-loaded sodium alginate microparticles was safe to nasal epithelium. In conclusion, spray drying of RH using sodium alginate polymer has produced microparticles of suitable characteristics for potential intranasal administration.

Composite material with nanoscale architecture based on bioapatite, sodium alginate and ZnO microparticles

A nanostructured composite material in the form of a hydrogel and beads based on hydroxyapatite (HA), sodium alginate (Alg) and ZnO microparticles was fabricated under the influence of microwave irradiation. An average crystallite size of the HA was 40 nm, while ZnO crystallites of the size 25 nm–11 µm were formed. The inorganic HA-ZnO phase of studied composite is distributed in the polysaccharide matrix of the alginate, which corresponds to the structures of natural bone nanocomposites. The introduction of ZnO into the composite increases its porosity up to 5 times and the degree of swelling in phosphate buffered saline up to 2 times, as well as provides weak antimicrobial activity. The effect of microwave and ultrasonic treatment on the structure of HA-ZnO and HA-Alg-ZnO composites’ microcrystals was studied. The mechanism of antimicrobial activity of ZnO crystals in the HA-Alg-ZnO composite was proposed. The in vitro biocompatibility and cytotoxicity of the synthesized materials was studied and it was found that addition of ZnO make insignificant effect on biocompatibility. Thus, the main goal of our work was fabrication of the bioactive material using microwave and ultrasonic treatment for additional enhancement of antibacterial properties.

The influence of new polymeric microbeads in peeling products on skin condition

The first aim of this work was to obtain the formula of peeling using sodium alginate microparticles and the second aim was to study the influence of this product on skin condition. Alginate microparticles were obtained by the extrusion method. The hydration, sebum, colour and skin's barrier quality were examined after application of peeling. The results showed that alginate microparticles doesn’t irritate the skin. After the application, redness of skin, itching and dryness didn’t appear and the dead skin cells were removed from the skin surface. Sodium alginate microparticles may be successfully used in cosmetic purposes as abrasive agent.

3D Porous Gelatin/PVA Hydrogel as Meniscus Substitute Using Alginate Micro-Particles as Porogens.

One of the current major challenges in orthopedic surgery is the treatment of meniscal lesions. Some of the main issues include mechanical consistency of meniscal implants, besides their fixation methods and integration with the host tissues. To tackle these aspects we realized a micro-porous, gelatin/polyvinyl alcohol (PVA)-based hydrogel to approach the high percentage of water present in the native meniscal tissue, recapitulating its biomechanical features, and, at the same time, realizing a porous implant, permissive to cell infiltration and tissue integration. In particular, we adopted aerodynamically-assisted jetting technology to realize sodium alginate micro-particles with controlled dimensions to be used as porogens. The porous hydrogels were realized through freezing-thawing cycles, followed by alginate particles leaching. Composite hydrogels showed a high porosity (74%) and an open porous structure, while preserving the elasticity behavior (E = 0.25 MPa) and high water content, typical of PVA-based hydrogels. The ex vivo animal model validation proved that the addition of gelatin, combined with the micro-porosity of the hydrogel, enhanced implant integration with the host tissue, allowing penetration of host cells within the construct boundaries. Altogether, these results show that the combined use of a water-insoluble micro-porogen and gelatin, as a bioactive agent, allowed the realization of a porous composite PVA-based hydrogel to be envisaged as a potential meniscal substitute.

Evaluation of eliciting activity of peptidil prolyl cys/trans isomerase from Pseudonomas fluorescens encapsulated in sodium alginate regarding plant resistance to viral and fungal pahogens.

Use of chemical pesticides poses a threat for environment and human health, so green technologies of crop protection are of high demand. Some microbial proteins able to activate plant defense mechanisms and prevent the development of resistance in plant pathogens, may be good alternative to chemicals, but practical use of such elicitors is limited due to need to protect them against adverse environment prior their delivery to target receptors of plant cells. In this study we examined a possibility to encapsulate heat resistant FKBP-type peptidyl prolyl cis-trans isomerase (PPIase) from Pseudomonas fluorescens, which possesses a significant eliciting activity in relation to a range of plant pathogens, in sodium alginate microparticles and evaluated the stability of resulted complex under long-term UV irradiation and in the presence of proteinase K, as well as its eliciting activity in three different “plant-pathogen” models comparing to that of free PPIase. The obtained PPIase-containing microparticles consisted of 70% of sodium alginate, 20% of bovine serum albumin, and 10% of PPIase. In contrast to free PPIase, which lost its eliciting properties after 8-h UV treatment, encapsulated PPIase kept its eliciting ability unchanged; after being exposed to proteinase K, its eliciting ability twice exceeded that of free PPIase. Using “tobacco-TMV”, “tobacco-Alternaria longipes”, and “wheat-Stagonospora nodorum” model systems, we showed that encapsulation process did not influence on the eliciting activity of PPIase. In the case of the “wheat-S. nodorum” model system, we also observed a significant eliciting activity of alginate-albumin complex and almost doubled activity of encapsulated PPIase as compared to the free PPIase. As far as we know, this is the first observation of a synergistic interaction between alginate and other compound possessing any bioactive properties. The results of the study show some prospects for a PPIase use in agriculture.

Ciprofloxacin-loaded sodium alginate/poly (lactic-co-glycolic acid) electrospun fibrous mats for wound healing

Wound dressings should ideally be able to maintain high humidity, remove excess wound exudate, permit thermal insulation, provide certain mechanical strength, and in some cases deliver antibiotics to prevent infections. Until now, none of the existing wound dressing products can meet all these requirements. To design a wound dressing with as many of the aforementioned features as possible, in this study, we attempted to prepare ciprofloxacin (CIP), an antibiotic, loaded electrospun hydrophobic poly (lactic-co-glycolic acid) (PLGA) fibrous mats modified with hydrophilic sodium alginate (ALG) microparticles. The results showed that ALG could improve the wettability, water absorption capacity, and enhance the release rate of ciprofloxacin from the PLGA fibrous mats. In addition, the addition of ALG reduced the stiffness of PLGA fibrous mats for better protection of the injured area as indicated by the Young’s modulus. Moreover, the burst release of CIP resulted from the addition of ALG seemed to provide an improved antimicrobial effect to the PLGA mats. This study demonstrated the potential of combining hydrophilic and hydrophobic polymers to design the desired wound dressings via the electrospinning process.

Polysaccharide hydrogel particles for enhanced delivery of hesperidin: Fabrication, characterization and in vitro evaluation

In the present contribution we focus on the fabrication and characterization of targeted delivery systems suitable for encapsulation of hesperidin (HESP) − a natural health-promoting flavonoid glycoside. We fabricated and extensively studied pH-responsive, biodegradable double-compartment hydrogel carriers composed of sodium carboxymethyl cellulose particles (ACP) filled with hesperidin-loaded sodium alginate microparticles (AMP). Additionally, hesperidin was encapsulated directly in sodium alginate or sodium carboxymethyl cellulose particles (AP or CP, respectively). The obtained carriers were characterized in respect to their morphology and size by using scanning electron microscopy (SEM). The cargo encapsulation was confirmed by spectroscopic analysis (FTIR), while the process efficacies were derived spectrophotometrically (UV–vis). The effect of different pH on the stability of the beads has been assessed. The in vitro release kinetics of the fabricated HESP-loaded particles was studied in simulated gastric and intestinal environments. The fabrication processes yielded stable particles of desired properties. Comparing the results obtained for both single- and double-compartment systems, makes it possible to conclude that the latter is superior in regard to prolonged delivery of hesperidin to the place of action under simulated intestinal conditions.

Ganoderma lucidum polysaccharide loaded sodium alginate micro-particles prepared via electrospraying in controlled deposition environments

Ganoderma lucidum polysaccharide (GLP) is a functional food source deployed in preventative medicine. However, applications utilizing GLP are limited due to oxidative and acidic environmental damage. Advances in preserving GLP structure (and therefore function), in situ, will diversify their applications within biomedical fields (drug and antibacterial active delivery via the enteral route). In this study, GLP loaded sodium alginate (NaAlg) micro-particles (size range 225–355μm) were generated using the electrospray (ES) process. The loading capacity and encapsulation efficiency of GLP for composite particles (collected at different temperatures) were ∼23% and 71%, respectively. The collection substrate (CaCl2, 1–20w/v%) concentration was explored and preliminary findings indicated a 10w/v% solution to be optimal. The process was further modified by manipulating the collection environment temperature (∼25 to 50°C). Based on this, NaAlg/GLP micro-particles were engineered with variable surface morphologies (porous and crinkled), without effecting the chemical composition of either material (GLP and NaAlg). In-vitro release studies demonstrated pH responsive release rates. Modest release of GLP from micro-particles in simulated gastric fluid (pH ∼1.7) was observed, while rapid release was exhibited under simulated intestinal conditions (pH ∼7.4). Release of GLP from NaAlg beads was the greatest from samples prepared at elevated environmental temperatures. These findings demonstrate a facile route to fabricate GLP-NaAlg loaded micro-particles with various shapes, surface topographies and release characteristics via a one-step ES process.

Immunization of rainbow trout (Oncorhynchus mykiss) with alginate microparticles containing inactivated Flavobacterium psychrophilum

In this study, survival rate of rainbow trout (Oncorhynchus mykiss), fed for 28 days with sodium alginate microparticles containing Flavobacterium psychrophilum inactivated with formalin, against diseases is determined. The fishes are divided into six groups in terms of feeding method; control group, sodium alginated group, fishmeals including 2.5 and 10 mg/g F. psychrophilum , fishmeals of 2.5 and 10 mg/g F. psychrophilum encapsulated with alginate microparticles. Following by oral immunization, experimental infection is created by bathing them in 3.2x107 CFU/ml F. psychrophilum for 1 hour at 53. and 87. days and relative percent survival (RPS) rates are determined. At fifth third day of immunization, while mortality rate of 79.2% is observed for control group, the highest RPS value of 62.1 is found for the group fed with 10 mg/g F. psychrophilum alginate microparticles. At eighty seventh day in infectious F. psychrophilum , while control group’s mortality rate is found 74.8, the rest of groups RPS rates are determined 30.48, 35.3, 40.10, 50.25 and 56.68 respectively. Based on these findings, it can be asserted that protectiveness of fishes, fed with fishmeal encapsulated with sodium alginate microparticles by using inactivated bacterial cells, is not achieved at a sufficient level. Keywords: Rainbow trout, Flavobacterium psychrophilum, sodium alginate microparticles, relative percent survival rates

Alginate microparticles loaded with lipopolysaccharide subunit antigen for mucosal vaccination against Klebsiella pneumoniae

Klebsiella pneumoniae (K. pneumoniae) is one of the commonest causes of nosocomial infections in human beings. Since K. pneumoniae infections are air borne type, controlling it by mucosal vaccination through nasal and pulmonary route could be a promising approach in order to simulate the natural infection. New vaccines such as subunit vaccines are safer than traditional vaccines, but they are less immunogenic. Therefore to enhance their immunogenicity, there is a need to develop potent and safe adjuvants and delivery systems. It has been established that micro-particles are one of the most potent adjuvants available for mucosal delivery of vaccines and they do so by improving uptake of encapsulated antigen by antigen presenting cells (APCs).Lipopolysaccharide (LPS), the antigenic fraction was extracted from K. pneumoniae by hot phenol extraction method. LPS loaded sodium alginate microparticles were prepared by emulsion ionic gelation method. Microparticles with particle size less than 5 μm were obtained. Loading efficiency of the LPS loaded microparticles ranged from 76 to 82 %. Comparative in vivo immunogenicity studies were carried for free LPS and encapsulated LPS, administered via intramuscular, intratracheal and intranasal routes in Swiss albino mice. The study revealed that LPS encapsulated microparticles exhibit greater efficacy when administered by intra-tracheal route as compared to free LPS vaccine.

Gastrointestinal transition and anti-diabetic effect of Isabgol husk microparticles containing gliclazide

Isabgol husk with sodium alginate was formulated into gliclazide loaded microparticles which were characterized for particle size, swelling index, entrapment efficiency, in vitro release, release kinetics, stability, hypoglycemic effect, surface morphology, and gastrointestinal transition. The particle size in different formulations varied from 752.83±0.630 to 872.03±0.293μm. It was analyzed by dissolution study that up to 98% of loaded gliclazide was released in simulated intestinal fluid (SIF, pH 7.4) within 8h. The formulations containing sodium alginate and Isabgol husk–sodium alginate showed bioequivalency with marketed sustained release tablets (Glizid MR 60®) in terms of release pattern. The drug maintained its integrity in terms of functional groups after fabrication in formulations as observed by FTIR analysis. The hypoglycemic effect of gliclazide loaded Isabgol husk–sodium alginate microparticles was found to be 37±6.356% in terms of changes of blood glucose level from base glucose level (100%) in diabetic condition after 24h of oral administration and it was more than marketed conventional tablets (95.5±3.286%). The retention of microparticles was observed in small intestine up to 10h during whole body X-ray imaging. The study revealed that microparticles composing of Isabgol husk may have the potential for regulating blood glucose level in diabetic animals with controlled release of gliclazide.

Induction of immune response in broiler chickens immunized with recombinant FliC and challenged by Salmonella Typhimurium

The study examined (1) the immune response in broiler chickens after oral immunization with recombinant flagellin (rFliC) from Salmonella Typhimurium conjugated with sodium alginate microparticles, and the immune response enhancement in association with recombinant cholera toxin B subunit protein (rCTB) and pool of Lactobacillus spp. (PL). The immune responses were evaluated by dosage of IgY serum and IgA from intestinal fluid and immunostaining of CD8+ T lymphocytes in the cecum. The immunized animals were challenged with Salmonella Typhimurium (ST) 21 days after treatment. In all immunized groups, a significant increase (p<0.05) was observed in IgA levels (μg/mL), especially three weeks after immunization. The serum IgY levels (μg/mL) were little affected by the treatments and differed significantly among groups only in the second post-immunization week (p<0.05). After the challenge, the number of CD8+ T cells differed significantly between the treatments and negative control. Retrieval of Salmonella Typhimurium was not detected at 48 hours after the challenge in T2 (rFliC+rCTb), T3 (rFliC+PL) and T4 (rFliC+rCTB PL). The rFliC administered orally with or without rCTB and Lactobacillus spp. produces significant induction of humoral immune response, and the immunized chickens were more effective in eliminating Salmonella after challenge.

Mucoadhesive microparticles as potential carriers in inhalation delivery of doxycycline hyclate: a comparative study

The present work compares and evaluates the suitability of different polymer-based microparticles for inhalation delivery of doxycycline hyclate. Mucoadhesive polymers, such as sodium carboxymethyl cellulose, sodium alginate, polyvinyl alcohol, polyvinylpyrrolidone, starch, and carbopol were selected as carriers for inhalation delivery. Microparticles were prepared by spray drying and evaluated in terms of yield, moisture content, morphology, tapped density, encapsulation efficiency, in vitro mucoadhesion, thermal properties and in vitro aerosolization performance. Additionally, the cytotoxicity of the microparticles on H1299 human alveolar cell line was examined. Smooth spherical to collapsed doughnut shaped particles were formed. They exhibited tap densities of 0.202–0.502g/cm3 and mass median aerodynamic diameter of 3.74–6.54μm. Mucoadhesion was highest in case of carbopol-based microparticles. Drug release from these microparticles exhibited biphasic Fickian type of diffusion. Only at the highest concentration of microparticles (1mg/mL) less than 90% cell viability was seen in DX loaded sodium alginate microparticles (DXSA, 87.2%), starch microparticles (DXST, 85.1%) and carbopol microparticles (DXCP, 82.7%) preparations after 48h of exposure to alveolar cells. The results clearly indicate that sodium carboxymethyl cellulose-based microparticles may serve as an ideal carrier for inhalation delivery of doxycycline hyclate.