Improved bioavailability of orally delivered insulin using Eudragit-L30D coated PLGA microparticles

Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62 +/- 1.8% and 17.5 +/- 1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29 +/- 1.01% and 88.30 +/- 1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37 degrees C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3 +/- 11% and 62.7 +/- 3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.     

Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets

The effects of alginate coated on tetracycline (Tc) loaded poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres fabricated by double emulsion solvent evaporation technique for local delivery to periodontal pocket were investigated. Alginate coated PLGA microspheres showed smoother surface but enlarged their particle sizes compared with those of uncoated ones. In addition, alginate coated microspheres enhanced Tc encapsulation efficiency (E.E.) from 11.5?±?0.5% of uncoated ones to 17.9?±?0.5%. Moreover, all of the coated PLGA microspheres even fabricated at different conditions could prolong Tc release from 9–12 days with 50% or higher in cumulative release of Tc compared with those of uncoated ones. The swelling ratios of PLGA microspheres for alginate coated or uncoated ones, one of the possible mechanisms for enhancing Tc release for the coated ones, were measured. The results showed that 20% or higher in swelling ratio for the coated microspheres at the earlier stage of hydration (e.g.?≤?24?h) could be an important factor to result in high Tc release compared to the uncoated ones. In conclusion, alginate coated Tc loaded PLGA microspheres could enhance Tc delivery to periodontal pocket by enhancing drug encapsulated efficiency, released quantities and sustained release period compared with uncoated ones.     

Influence of an enteric polymer on drug release rates of theophylline from pellets coated with Eudragit RS 30D

The purpose of this research study was to investigate the influence of an enteric polymer on the drug release properties of theophylline pellets coated with Eudragit RS 30D. Theophylline pellets were coated with aqueous colloidal dispersions of Eudragit RS 30D containing various amounts of Eudragit L 100-55. The effect of storage conditions on the release of drug from coated pellets was determined as a function of the pH of the dissolution medium. The results from the dissolution study showed significant changes in the dissolution rate of theophylline from pellets coated with Eudragit RS 30D when cured at 40 degrees C for 4 days. No change in the drug release rate was observed when Eudragit L100-55 was present in the Eudragit RS 30D dispersion. Increasing the ratio of Eudragit L100-55 to Eudragit RS 30D resulted in faster drug release rates from the coated pellets. An increase in the pH of the dissolution medium was found to enhance drug release from the pellets coated with Eudragit RS 30D containing Eudragit L 100-55. Theophylline pellets when coated with Eudragit RS 30D containing the enteric polymer Eudragit L100-55 demonstrated no aging effects when stored at elevated temperatures. The overcoating of the pellets with Eudragit RD 100 did not affect the drug release profiles and prevented the particles from agglomerating during curing and storage.     

Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon

A microparticulate system consisting of non-enzymatically degrading poly(dl-lactide-co-glycolide) (PLGA) core and delivering budesonide site specifically to distal ileum and colon was developed. Budesonide-loaded microparticles were fabricated using solvent evaporation technique and formulation variables studied included different molecular weight grades of PLGA polymer as well as concentration of polymer, surfactant and drug. Eudragit S-100, an enteric polymer, was then used to form a coating on the surface of budesonide-loaded PLGA microparticles for site specific delivery to the distal ileum and colon. Budesonide-loaded PLGA microparticles prepared from various formulation parameters showed mean encapsulation efficiencies ranging between 50% and 85% and mean particle size ranging between 10 and 35mum. In vitro release kinetics studies showed a biphasic release pattern with an initial higher release followed by a slower drug release. Increasing polymer and surfactant concentrations exhibited sharply contrasting drug release profiles, with increasing polymer concentrations resulting in a lower drug release and vice versa. The budesonide-loaded PLGA microparticles coated with Eudragit S-100 coating showed a decrease in entrapment efficiency with an accelerated in vitro drug release. Moreover, complete retardation of drug release in an acidic pH, and, once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microparticles were observed. From the results of this investigation, the application of double microencapsulation technique employing PLGA matrix and Eudragit S-100 coating shows promise for site specific and controlled delivery of budesonide in Crohn's disease.     

Controlled release behaviour of protein-loaded microparticles prepared via coaxial or emulsion electrospray

Biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles are an effective way to achieve sustained drug release. In this study, we investigated a sustained release model of PLGA microparticles with incorporated protein via either emulsion or coaxial electrospray techniques. PLGA (75:25) was used as the carrier, and bovine serum albumin as a model protein. Coaxial electrospray resulted in a type of core–shell structure with mean diameters of 2.41?±?0.60?µm and a centralised protein distribution within the core. Emulsion electrospray formed bigger microparticles with mean diameters of 22.75?±?8.05?µm and a heterogeneous protein distribution throughout the microparticles. The coaxial electrospray microparticles presented a much slighter burst release than the emulsion electrospray microparticles. Loading efficiency was significantly higher (p?<?0.05) in the coaxial group than emulsion group. This indicated that both emulsion and coaxial electrospray could produce protein-loaded microparticles with sustained release behaviour, but the former revealed a superior approach for drug delivery.     

磷酸川芎嗪丙烯酸树脂水分散体包衣小丸的体外释放研究

目的：研究磷酸川芎嗪丙烯酸树脂水分散体包衣缓释小丸的体外释药。方法：采用丙烯酸树脂RS30D和丙烯酸树脂RL30D混合液包衣制备磷酸川芎嗪缓释小丸，并考察包衣混合液中两种丙烯酸树脂水分散体比例、包衣增重、溶出介质pH对磷酸川芎嗪包衣制剂体外释药的影响。结果：随着包衣液中丙烯酸树脂RL30D/丙烯酸树脂RS30D比例增大、包衣增重降低、溶出介质pH增大，释药速率加快。结论：包衣液中丙烯酸树脂RL30D/丙烯酸树脂RS30D比例、包衣增重、溶出介质pH均显著影响制剂药物释放。     

Preparation and characterization of biodegradable urea-loaded microparticles as an approach for transdermal delivery

This work describes the formulation and characterization of urea-loaded microspheres prepared using various polymers such as ethyl cellulose (EC), cellulose acetate phthalate (CAP) and poly (D,L-lactic-co-glycolic acid) (PLGA), along with the utilization of a solvent evaporation technique. The effect of various formulation parameters (i.e. polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, drug/polymer ratio, homogenizer and stirrer speed, sonication time and speed, type of washing solution, drying and separation method) on the characteristics of microspheres was also evaluated. Results obtained indicated that, in the presence of urea, highest rate of EC microsphere production could be obtained at a drug/polymer ratio of 1:2 and a polymer solution/vehicle volume ratio of 1:50. In some cases, crystallization of urea was observed during the encapsulation process using cellulose derivative polymers. CAP microparticles showed a rough and tortuous surface while EC microparticles had a wider range of particle size. However, with the PLGA polymer, much better desired microparticles with a smaller size range of 1–3?µm were obtained. In general, PLGA microspheres were spherical in shape and possessed smooth surfaces with less pores in comparison with those obtained by the other polymers. The yield of particle production and the extent of urea encapsulation in PLGA particles were measured to be 68.87%?±?5.3 and 40.5%?±?3.4, respectively. The release study from PLGA microspheres revealed that up to 70% of the drug was released within a few days, through a four-stage release pattern.     

Controlled release from coated polymer microparticles embedded in tissue-engineered scaffolds

The controlled release of proteins in tissue-engineered implants is being examined with the potential application to improve vascularization and hasten tissue growth. Bovine serum albumin (BSA), was encapsulated within poly(D,L-lactic-co-glycolic acid) [PLGA] microparticles. The microparticles were coated with poly(vinyl alcohol) and incorporated into PLGA tissue-engineered scaffolds during fabrication. The release of BSA from PLGA microparticles, coated PLGA microparticles, and microparticles embedded in a porous PLGA scaffold was measured. We have developed a novel approach that will permit incorporation of coated polymeric microparticles during PLGA scaffold fabrication. Growth factors or drugs could be incorporated into the microparticles resulting in a long-term, controlled release.     

Effect of substitution of plasticizer dibutyl phthalate with dibutyl sebacate on Eudragit® RS30D drug release rate control

In the current study, the influence of type of plasticizer used with Eudragit^® RS 30D on the drug release was investigated in solid dosage form extrusion/spheronization, and film coating. The drug pellets were coated for controlling drug release with Eudragit^® RS 30D containing dibutyl phthalate and compared with dibutyl sebacate as an alternative plasticizer. To study the influence of pH of the dissolution medium on the drug release profile, capsules are tested for drug release profile at pH 1.2, 4.4, and 6.3. Additionally, the aging effect on the curing of Eudragit^® RS 30D is evaluated by exposing the capsules dosage form to room temperature (25?°C?±?2?°C/60%?±?5% RH) for time 0, 3, 6, and 9?months, accelerated temperature (40?°C?±?2?°C/75%?±?5% RH) for time 0, 3, and 6?months, and intermediate temperature (30?°C?±?2?°C/65%?±?5% RH) for time 0, 6, and 9?months. The replacement of dibutyl phthalate, with dibutyl sebacate for polymer coating system in similar concentration is comparable with respect to plasticization effect. The coalescence of the polymer particles is not changed and requires no additional processing parameter control or additional curing time.     

Controlled Release from Coated Polymer Microparticles Embedded in Tissue-engineered Scaffolds

The controlled release of proteins in tissue-engineered implants is being examined with the potential application to improve vascularization and hasten tissue growth. Bovine serum albumin (BSA), was encapsulated within poly(D,L-lactic-co-glycolic acid) [PLGA] microparticles. The microparticles were coated with poly(vinyl alcohol) and incorporated into PLGA tissue-engineered scaffolds during fabrication. The release of BSA from PLGA microparticles, coated PLGA microparticles, and microparticles embedded in a porous PLGA scaffold was measured. We have developed a novel approach that will permit incorporation of coated polymeric microparticles during PLGA scaffold fabrication. Growth factors or drugs could be incorporated into the microparticles resulting in a long-term, controlled release.     

Enteric coated HPMC capsules designed to achieve intestinal targeting.

The enteric coating of HPMC capsules containing paracetamol was investigated. Two enteric polymers, Eudragit L 30 D-55 and Eudragit FS 30 D were studied, which are designed to achieve enteric properties and colonic release, respectively. The capsules were coated in an Accela Cota 10, and, as shown by optical microscopy, resulted in capsules with a uniform coating. Scanning electron microscopy of the surface of the capsules illustrate that, in contrast to gelatin, HPMC has a rough surface, which provides for good adhesion to the coating. Dissolution studies demonstrated that capsules coated with Eudragit L 30 D-55 were gastro resistant for 2 h at pH 1.2 and capsules coated with Eudragit FS 30 D were resistant for a further 1 h at pH 6.8. The product visualisation technique of gamma scintigraphy was used to establish the in vivo disintegration properties of capsules coated with 8 mg cm(-2) Eudragit L 30 D-55 and 6 mg cm(-2) Eudragit FS 30 D. For HPMC units coated with Eudragit L 30 D-55, complete disintegration occurred predominately in the small bowel in an average time of 2.4 h post dose. For HPMC capsules coated with Eudragit FS 30 D, complete disintegration did not occur until the distal small intestine and proximal colon in an average time of 6.9 h post dose.     

Insulin-loaded PLGA microspheres for glucose-responsive release

Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N–vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83?±?0.15 and 82.6?±?5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.     

Evaluation of Mucoadhesive PLGA Microparticles for Nasal Immunization

In this study, hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared and coated with chitosan and trimethyl chitosan (TMC) to evaluate the effect of coating material for nasal vaccine delivery. The developed formulations were characterized for size, zeta potential, entrapment efficiency, and mucin adsorption ability. Plain PLGA microparticles demonstrated negative zeta potential. However, coated microparticles showed higher positive zeta potential. Results indicated that TMC microparticles demonstrated substantially higher mucin adsorption when compared to chitosan-coated microparticles and plain PLGA microparticles. The coated and uncoated microparticles showed deposition in nasal-associated lymphoid tissue under fluorescence microscopy. The coated and uncoated microparticles were then administered intranasally to mice. Immune-adjuvant effect was determined on the basis of specific antibody titer observed in serum and secretions using enzyme-linked immunosorbent assay. It was observed that coated particles showed a markedly increased anti-HBsAg titer as compared to plain PLGA microparticles, but the results were more pronounced with the TMC-coated PLGA microparticles.     

In vitro release and in vivo absorption in beagle dogs of meloxicam from Eudragit FS 30 D-coated pellets

The objective of this study was to develop meloxicam-loaded colon-specific pellets coated with Eudragit FS 30 D and further evaluate their in vitro release and in vivo absorption in beagle dogs. Meloxicam-loaded cores (drug loading, 4.8%, w/w) were prepared by layering drug-binder (HPMC)-solubilizer (beta-cyclodextrin) solution onto nonpareils (710-850 microm) and then coated with a copolymer of methyl acrylate, methyl methacrylate and methacrylic acid (Eudragit FS 30 D). The obtained pellets with 15% (w/w) coating level had a spherical form and a smooth surface with coating thickness approximately 28 microm. The in vitro drug release from the pellets was pH-dependent with sufficient gastric resistance (pH 1.2: no release; pH 6.8: 6%; pH 7.0: 52%; pH 7.2: 100%; pH 7.4: 100%, after 3 h incubation). In vivo study was carried out using pentagastrin-pretreated beagle dogs. The onset of meloxicam absorption from the coated pellets with 15% (w/w) Eudragit FS 30 D (3.0+/-0.8 h) was significantly delayed (p<0.05) compared to that from the uncoated drug-layered cores (0.6+/-0.3 h). The area under the meloxicam plasma concentration-time curve (AUC(0-->96)(h) was not significantly different between the two preparations (p>0.05), although AUC(0-->96)(h) obtained after oral administration of coated pellets (142.5+/-59.6 microg h/ml) was lower than that obtained after administration of uncoated drug-layered cores (180.8+/-61.9 microg h/ml). These results suggested that meloxicam could be delivered to the colon with 15% (w/w) coating level of Eudragit FS 30 D and this polymer coating had no significant influence on the relative bioavailability of meloxicam of the pellets.     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg^?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h^?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.     

Design of taste masked enteric orodispersible tablets of diclofenac sodium by applying fluid bed coating technology

Diclofenac sodium (DS) a non-steroidal anti-inflammatory drug has a bitter taste and is a local stomach irritant. The aim of this study was to formulate taste masked DS orally dispersible tablets (ODTs) with targeted drug release in the intestine. Pellets of DS were designed using sugar sphere cores layered with DS followed by an enteric coat of Eudragit L100 and a second coat of Eudragit E100 for taste masking. The produced pellets had a high loading efficiency of 99.52% with diameters ranging from 493.7 to 638.9?µm. The prepared pellets were spherical with smooth surfaces on scanning electron microscopy examination. Pellets with the 12% enteric coat Eudragit L100 followed by 5% Eudragit E 100 resulted in 1.4?±?0.5% DS release in simulated gastric fluid (SGF) and complete dissolution in simulated intestinal fluid (SIF). The pellets were then used to formulate ODTs. In vitro disintegration time of ODTs ranged from 20?±?0.26 to 46?±?0.27?s in simulated saliva fluid (SSF). Dissolution was less than 10% in SGF while complete drug release occurred in SIF. The release rate was higher for the optimized formulation (F12) in SIF than for the marketed product Voltaren® 25?mg tablets. The optimized ODTs formulation had a palatable highly acceptable taste.     

Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets

The effects of alginate coated on tetracycline (Tc) loaded poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres fabricated by double emulsion solvent evaporation technique for local delivery to periodontal pocket were investigated. Alginate coated PLGA microspheres showed smoother surface but enlarged their particle sizes compared with those of uncoated ones. In addition, alginate coated microspheres enhanced Tc encapsulation efficiency (E.E.) from 11.5 +/- 0.5% of uncoated ones to 17.9 +/- 0.5%. Moreover, all of the coated PLGA microspheres even fabricated at different conditions could prolong Tc release from 9-12 days with 50% or higher in cumulative release of Tc compared with those of uncoated ones. The swelling ratios of PLGA microspheres for alginate coated or uncoated ones, one of the possible mechanisms for enhancing Tc release for the coated ones, were measured. The results showed that 20% or higher in swelling ratio for the coated microspheres at the earlier stage of hydration (e.g. < or = 24 h) could be an important factor to result in high Tc release compared to the uncoated ones. In conclusion, alginate coated Tc loaded PLGA microspheres could enhance Tc delivery to periodontal pocket by enhancing drug encapsulated efficiency, released quantities and sustained release period compared with uncoated ones.     

Release optimization of epidermal growth factor from PLGA microparticles

Abstract

The objective of this study was to prepare poly lactic-co-glycolic acid (PLGA)-based microparticles as potential carriers for recombinant human epidermal growth factor (rhEGF). In order to optimize characteristic parameters of protein-loaded microspheres, bovine serum albumin (BSA) was selected as the model protein. To reduce burst release as a common problem of microspheres, a proper alteration in the particle composition was used, such as addition of poly vinyl alcohol and changes in initial drug loading. The effects of these parameters on particle size, encapsulation efficiency and in vitro release kinetics of BSA in PLGA microspheres were investigated using a Box–Behnken response surface methodology. The biological activity of the released rhEGF was assessed using human skin fibroblasts cell proliferation assay. The prepared rhEGF-loaded microspheres had an average size of 6.44?±?2.45?µm, encapsulation efficiency of 97.04?±?1.13%, burst release of 13.06?±?1.35% and cumulative release of 22.56?±?2.41%. The proliferation of human skin fibroblast cells cultivated with rhEGF releasate of microspheres was similar to that of pure rhEGF, indicating the biological activity of released protein confirming the stability of rhEGF during microsphere preparation. These results are in agreement with the purpose of our study to prepare rhEGF-entrapped PLGA microparticles with optimized characteristics.     

Stability and release characteristics of poly(D,L-lactide-co-glycolide) encapsulated CaPi-DNA coprecipitation

The aims of this work were to determine the stability of DNA-calcium-phosphate coprecipitation (CaPi-DNA) against various conditions during double emulsification microencapsulation and assess the release and physicochemical characteristics of poly(D,L-lactide-co-glycolide) (PLGA) microparticles loading CaPi-DNA. CaPi-DNA prepared at pH 6.5 showed a good stability with over 60% CaPi-DNA remained after emulsification, but no more than 40% at pH 8.0. Polyvinyl alcohol (PVA, 1-5%) could make over 80% CaPi-DNA (pH 7.0) preserved after homogenization. The dichloromethane (DCM), mixture of DCM and ethyl acetate, ether and n-hexane (1:1) exhibited neglectable influence on CaPi-DNA under homogenization. PLGA had influenced on CaPi-DNA without any additional stabilizer, in particular, PLGA (75:25, 4%, w/v) demonstrated a profound damage with only about 10% of the original CaPi-DNA remained. PLGA microparticles loading CaPi-DNA were spherical in shape with size range of 2.0-5.0microm, and entrapment efficiency 30-50%. CaPi-DNA was found to increase the stability of pDNA in PLGA microparticles without losing its structure integrity. The release of CaPi-DNA from microparticles showed a low burst release (<7.5%) within 24h and following sustained release process. The amount of cumulated CaPi-DNA release over 30 days was: 17.6% for PLGA (lactide:glycolide=50:50), 27.3% for PLGA (65:35) and 44.8% for PLGA (75:25) microparticles, respectively. The encapsulation of CaPi-DNA in microparticles could significantly protect CaPi-DNA from degradation of nuclease with average over 80% of total DNA recovery. These results suggested that the encapsulation of CaPi-DNA in PLGA microparticles could improve stability of pDNA.     

Long circulating PEGylated PLGA nanoparticles of cytarabine for targeting leukemia

The present investigation was aimed at developing PEGylated PLGA nanoparticles of cytarabine. PLGA Nanoparticles were prepared by modified nanoprecipitation method, optimized for mean particle size (152?±?6?nm) and entrapment efficiency (41.1?±?0.8%) by a 3² factorial design. The PEGylated PLGA nanoparticles of cytarabine had a zeta potential of ?7.5?±?1.3?mV and sustained the release of cytarabine for 48?h by Fickian diffusion. The IC₅₀ values for L1210 cells were 6.5, 5.3, and 2.2?µM for cytarabine, cytarabine loaded PLGA nanoparticles and cytarabine loaded PLGA-mPEG nanoparticles respectively. Confocal microscopy and flow cytometry showed that the nanoparticles were internalized by the L1210 cells and not simply bound to their surface. Biodistribution studies showed that the PEGylated nanoparticles of cytarabine were present in significantly higher concentrations in blood circulation as well as in brain and bones and avoided RES uptake as compared to the free drug.