Sequential Release of Paclitaxel and Imatinib from Core–Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core–shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core–shell microparticles were of spherical appearance, with an average size of 14.65 μm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core–shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.     

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.     

Sustained release of dexamethasone from drug‐loading PLGA scaffolds with specific pore structure fabricated by supercritical CO2 foaming

Inducing differentiation of bone marrow stem cells to generate new bone tissue is highly desirable by controlling the release of some osteoinductive or osteoconductive factors from porous scaffolds. In this study, dexamethasone was selected as a representative of small molecule drugs and dexamethasone‐loading porous poly(lactide‐co‐glycolide) (PLGA) scaffolds were successfully fabricated by supercritical CO₂ foaming. Scanning electron microscopy images showed that scaffolds had rough and relatively interconnected pores facilitating cells adhesion and growth. Specially, dexamethasone which was incorporated into PLGA matrix in a molecularly dispersed state could serve as a nucleation agent to be helpful for the formation of interconnected pores. Dexamethasone‐loading porous PLGA scaffolds exhibited sustained release profile, and the delivery of dexamethasone from porous scaffolds could last for up to 2 months. The cumulative released amount of dexamethasone was relevant with drug loading capacity (1.66%–2.95%) and pore structure of scaffolds; while the release behavior was anomalous (non‐Fickian) transport by fitting with the simple exponential equation, which had a diffusional exponent n higher than 0.5. It is feasible to fabricate drug‐loading porous scaffolds by supercritical CO₂ foaming with specific pore structure and sustained release profile, which can be well applied in bone tissue engineering. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46207.     

Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery

The aim of the present study was to develop the PLGA/HP55 nanoparticles with improved hypoglycemic effect for oral insulin delivery. The insulin-loaded PLGA/HP55 nanoparticles were produced by a modified multiple emulsion solvent evaporation method. The physicochemical characteristics, in vitro release of insulin, and in vivo efficacy in diabetic rats of the nanoparticles were evaluated. The insulin encapsulation efficiency was up to 94%, and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. When administered orally (50 IU/kg) to diabetic rats, the nanoparticles can decrease rapidly the blood glucose level with a maximal effect between 1 and 8 h. The relative bioavailability compared with subcutaneous injection (5 IU/kg) in diabetic rats was 11.3% ± 1.05%. This effect may be explained by the fast release of insulin in the upper intestine, where it is better absorbed by the high gradient concentration of insulin than other regions. These results show that the PLGA/HP55 nanoparticles developed in the study might be employed as a potential method for oral insulin delivery.     

Functionalized silver doped hydroxyapatite scaffolds for controlled simultaneous silver ion and drug delivery

Bacterial infections are a major problem in bone tissue regeneration, thus it is essential to incorporate antibacterial properties within the bone scaffolds. Silver compounds are frequently used as antibacterial agents to prevent bacterial infections and numerous studies have shown that silver ions can be incorporated within the biocompatible and osteoconductive biomaterial hydroxyapatite (HAp) structure, but, so far, no study has thoroughly evaluated silver ion release rates in long term. Therefore, we have established a novel carrier system for local drug delivery based on functionalized silver doped hydroxyapatite with determined long term silver ion release rates. Silver ions from prepared scaffolds were released with a rate of 0.001±0.0005 wt%/h taking into account the incorporated silver amount. Moreover, lidocaine hydrochloride was incorporated in the prepared scaffolds, to provide local anesthetic effect. These scaffolds were functionalized with sodium alginate and chitosan and in vitro drug release rate in simulated body fluid was evaluated. The results suggested that the developed novel composite scaffolds possess the antibacterial activity up to one year as well as controlled anesthetic drug delivery up to two weeks.     

Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment

A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment.     

In vitro release of complexed pDNA from biodegradable polymer films

The controlled delivery of low‐molecular weight drugs and proteins from biodegradable polymers has received considerable attention. However, controlled release studies of pDNA from such polymers have not been reported to date. In this study, a plasmid DNA was complexed with the cationic polymer called polyethylenimine (PEI). This gene vector has been shown to be very effective in transfecting cells. The complexed DNA were then incorporated into different types of poly‐lactic‐co‐glycolic acid (PLGA) film; PLGA 53/47 (M_w 90 kDa), 50/50 (M_w 11 kDa, end group is lauryl ester) and 75/25 (M_w 120 kDa). Their release profiles from a buffer solution were studied. An initial (small) burst release of PEI‐DNA from film was observed in PLGA 53/47 and 50/50, followed by a plateau phase and finally a rapid erosion‐controlled release. For PLGA 50/50, the rapid release started after 14 days; erosion‐controlled release for PLGA 53/47 started after 9 days; for PLGA 75/25, the release rate was governed by an initial burst release (10%) followed by a slow release controlled by diffusion. No obvious erosion‐controlled release rate was observed for this polymer up to 27 days. Thus, the controlled release of complexed DNA follows the general features exhibited by lower‐ M_w drugs. This is of significance in designing gene vector matrices that offer the promise of more lasting gene therapy compared with particulate formulations. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Biosurfactant-and-Bioemulsifier Produced by a Promising Cunninghamella echinulata Isolated from Caatinga Soil in the Northeast of Brazil

A Mucoralean fungus was isolated from Caatinga soil of Pernambuco, Northeast of Brazil, and was identified as Cunninghamella echinulata by morphological, physiological, and biochemical tests. This strain was evaluated for biosurfactant/bioemulsifier production using soybean oil waste (SOW) and corn steep liquor (CSL) as substrates, added to basic saline solution, by measuring surface tension and emulsifier index and activity. The best results showed the surface water tension was reduced from 72 to 36 mN/m, and an emulsification index (E₂₄) of 80% was obtained using engine oil and burnt engine oil, respectively. A new molecule of biosurfactant showed an anionic charge and a polymeric chemical composition consisting of lipids (40.0% w/w), carbohydrates (35.2% w/w) and protein (20.3% w/w). In addition, the biosurfactant solution (1%) demonstrated its ability for an oil displacement area (ODA) of 37.36 cm², which is quite similar to that for Triton X-100 (38.46 cm²). The stability of the reduction in the surface water tension as well as of the emulsifier index proved to be stable over a wide range of temperatures, in pH, and in salt concentration (4%–6% w/v). The biosurfactant showed an ability to reduce and increase the viscosity of hydrophobic substrates and their molecules, suggesting that it is a suitable candidate for mediated enhanced oil recovery. At the same time, these studies indicate that renewable, relatively inexpensive and easily available resources can be used for important biotechnological processes.     

Optimization of protein encapsulation in PLGA nanoparticles

Influences of process parameters were investigated on the efficiency of encapsulation of bovine serum albumin (BSA) in poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles produced by w₁/o/w₂ (water-in-oil-in-water) double emulsion-solvent evaporation method. According to a 5-factorial 3-level Box-Behnken type experimental design aqueous solution of BSA was emulsified in an immiscible organic phase composed of dichloromethane and various quantities of dissolved PLGA to get water-in-oil (w₁/o) emulsion. This latter was then dispersed in a second aqueous phase (w₂) containing poly-vinyl-alcohol (PVA) surfactant as an emulsifier/stabilising agent. PLGA nanoparticles with encapsulated BSA were obtained by evaporating the dichloromethane from the w₁/o droplets. Encapsulation efficiency was determined as the weight ratio of BSA remained in the PLGA nanoparticles relative to the total weight of BSA used in the process. By statistical evaluation of the experimental results an equation was proposed to predict the encapsulation efficiency as a function of five process variables. Two optimization procedures were carried out to increase the efficiency of encapsulation, with and without constraints referring to the required mean particle size. Correlation was found between the latter and the achievable maximal encapsulation efficiency under optimal process conditions.     

Fabrication and characterization of dual drug-loaded poly (lactic-co-glycolic acid) fiber-microsphere composite scaffolds

The purpose of this work is to develop dual drug-loaded poly (lactic-co-glycolic acid) (PLGA) fiber-microsphere composite scaffolds with desired morphologies and dual drug loading properties, and to investigate the release kinetics of the dual drugs, both hydrophobic and hydrophilic, from the composite scaffolds. In this study, simvastatin (SIM) and bovine serum albumin (BSA) were used as model drugs, which were incorporated into the composite scaffolds by performing electrospinning and emulsion electrospraying simultaneously. The optimum condition for electrospraying (solution concentration: 0.06?g/mL; applied voltage: 15?kV; and flow rate: 0.6?mL/h) has been obtained to prepare PLGA microspheres. The release rate of SIM and BSA from the composite scaffolds fit the first order kinetics and the Higuchi model, respectively. The results indicated that fiber-microsphere composite scaffolds had the ability to load two types of drug, suggesting the scaffolds have great potential in the field of tissue engineering and combined therapies.     

Systematic approach to treat chronic osteomyelitis through ceftriaxone-sulbactam impregnated porous β-tri calcium phosphate localized delivery system

Present investigation deals with in vitro and in vivo experimentation to treat chronic osteomyelitis, using pure β-tri calcium phosphate porous scaffolds. A novel approach was given to treat such infections using the scaffolds and drug combinations consisting of ideal antibiotics. In vitro studies include variation of porosity with interconnectivity, pore-drug interfacial studies by SEM-EDAX and drug elution studies both in contact with PBS and SBF at ca. 37 °C. In vivo trials were based on experimental osteomyelitis in rabbit model in tibia by Staphylococcus aureus. Characterizations included histopathology, radiology and estimation of drug in both bone and serum for 42 days by HPLC and subsequent bone-biomaterial interface by SEM. Samples having 60-65% porosity with average pore size ca. 55 μm and higher interconnectivity (22-113 μm), high adsorption efficiency (ca. 79%) of drug showed prolonged, sustained release of the drugs considered being sufficient to treat chronic osteomyelitis with desirable bone formation.     

Dual Delivery of BMP-2 and bFGF from a New Nano-Composite Scaffold,Loaded with Vascular Stents for Large-Size Mandibular Defect Regeneration

The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs), bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA). AlamarBlue assay and alkaline phosphatase (ALP) activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01). In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large bone defects in bone tissue engineering.     

Toxicological Assessment of Inhaled Nanoparticles: Role of in Vivo,ex Vivo,in Vitro,and in Silico Studies

The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced in vitro models, not only in vivo, but also cellular studies can be used for toxicological testing. Advanced in vitro studies use combinations of cells cultured in the air-liquid interface. These cultures are useful for particle uptake and mechanistic studies. Whole-body, nose-only, and lung-only exposures of animals could help to determine retention of NPs in the body. Both approaches also have their limitations; cellular studies cannot mimic the entire organism and data obtained by inhalation exposure of rodents have limitations due to differences in the respiratory system from that of humans. Simulation programs for lung deposition in humans could help to determine the relevance of the biological findings. Combination of biological data generated in different biological models and in silico modeling appears suitable for a realistic estimation of potential risks by inhalation exposure to NPs.     

In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.     

Development of Biodegradable Nanocarriers Loaded with a Monoclonal Antibody

Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid) (PLGA) nanoparticles using a water/oil/water double emulsion solvent evaporation technique. This method can be used to prepare protective polymeric nanoparticles for transporting functional antibodies to the cytoplasmic compartment of cancer cells. Nanoparticles were formulated and then characterized using a number of physical and biological parameters. The average nanoparticle size ranged from 221 to 252 nm with a low polydispersity index. Encapsulation efficiency of 16%–22% and antibody loading of 0.3%–1.12% were observed. The antibody molecules were released from the nanoparticles in a sustained manner and upon release maintained functionality. Our studies achieved successful formulation of antibody loaded polymeric nanoparticles, thus indicating that a PLGA-based antibody nanoformulation is a promising intracellular delivery vehicle for a large number of new intracellular antibody targets in cancer cells.     

Production and evaluation of vildagliptin-loaded poly(dl-lactide) and poly(dl-lactide-glycolide) micro-/nanoparticles: Response surface methodology approach

A laboratory scale spray dryer was used to encapsulate vildagliptin (VLG), an antihyperglycemic drug, into different polymers such as poly(dl-lactide) (PDLA), poly(dl-lactide-glycolide)-50:50 (PLGA 50:50), and poly(dl-lactide-glycolide)-75:25 (PLGA 75:25). Response surface methodology (RSM) was employed to evaluate the effects of process and formulation factors on the encapsulation efficiency (EE). The physicochemical properties of the drug-loaded micro-/nanoparticles, mainly the drug loading (DL), particle size distribution, surface morphology, drug–polymer compatibility, and release rate were investigated. % EE of drug-loaded micro-/nanoparticles were in the range of 57.10% to 76.44%. PLGA50:50 micro-/nanoparticles showed highest EE as compared to PDLA and PLGA75:25 micro-/nanoparticles. The mean particle size of the micro-/nanoparticles containing PLGA 50:50, PLGA 75:25, and PDLA polymers were 428?nm, 640?nm, and 1.22 µm, respectively. Surface morphology study revealed smooth, spherical and nonporous surface structures of the micro-/nanoparticles. Fourier transform infrared spectroscopy studies confirmed the drug–polymer compatibility. Powder X-ray diffraction analysis of micro-/nanoparticles revealed that VLG was present in the amorphous form within the micro-/nanoparticles formulations. In vitro release study demonstrated that VLG is slowly released from micro-/nanoparticles for 12?h and the drug release rate was influenced by type and viscosity of polymers used. This work suggests that PDLA, PLGA 50:50, and PLGA75:25 polymers are able to sustain the VLG release rates from micro-/nanoparticles.     

The Evaluation of the Possibilities of Using PLGA Co-Polymer and Its Composites with Carbon Fibers or Hydroxyapatite in the Bone Tissue Regeneration Process �C in Vitro and in Vivo Examinations

Synthetic polymers belonging to the aliphatic polyester group have become highly promising biomaterials for reconstructive medicine. The purpose of the present work is a biological evaluation of lactide-glycolide co-polymer (PLGA) and its composites with carbon fibers (PLGA+CF) or hydroxyapatite (PLGA+HA). The cytotoxicity of the evaluated materials towards hFOB 1.19 human osteoblast-like cells was assessed. Moreover, during the one-year contact of the assessed materials with living osseous tissue, the progress of bone formation was analyzed and the accompanying process of the materials’ degradation was evaluated. The materials under evaluation proved to be biocompatible.     

In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.     

Preparation and drug release behaviors of 5‐fluorouracil loaded poly(glycolide‐co‐lactide‐co‐caprolactone) nanoparticles

5‐Fluorouracil (5‐Fu) loaded poly(glycolide‐co‐lactide‐co‐caprolactone) (PGLC) nanoparticles were prepared by modified spontaneous emulsification solvent diffusion method (modified‐SESD method) and characterized by dynamic light scattering, scanning electron microscopy and ¹H NMR determination. It was found that the obtained nanoparticles showed near spherical shape and was controllable with the radius range of 30–100 nm. Compared with the nanoparticles prepared by polylactide and poly (lactide‐co‐glycolide) (PLGA) under the similar preparation condition, yield of PGLC nanoparticles was the highest, which reached to about 100%. On the other hand, drug entrapment efficiency of PGLC nanoparticles was also higher than that of PLGA and PLLA nanoparticles. 5‐Fu release behavior of PGLC nanoparticles in vitro showed that 5‐Fu release of PGLC nanoparticles showed a near zero‐order release profile, and 5‐Fu release rate of PGLC nanoparticles was faster than that of PLLA and PLGA nanoparticles. According to degradation behavior of PGLC nanoparticles, it could be proposed that the kinetic of degradation controlled release played an important role in the release process of PGLC nanoparticles. It revealed that the PGLC nanoparticles could be a promising drug carrier. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Impact of PLGA molecular behavior in the feed solution on the drug release kinetics of spray dried microparticles

The purpose of this study was to understand the impact of the poly (lactic-co-glycolic acid) (PLGA) molecular behavior in the feed solution on the drug release kinetics of PLGA microparticles prepared via spray drying. The PLGA molecular behavior in the feed solutions were characterized by using tube viscometry, which provides information about the polymer coil radius (R_coil), the Martin constant (K_m), and the overlap concentration (c*). The particle size and the drug surface enrichment were investigated by using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively. The drug release profiles were characterized by using the USP paddle method and analyzed by using the Crank's diffusion model to calculate the kinetic parameters. Multivariate data analysis using principal component analysis (PCA) was employed to display the relationship between the PLGA molecular behavior, particle properties and the drug release kinetics from the spray dried PLGA microparticles. Rheological studies suggested that an increased molar ratio of a poor solvent (methanol) in the solvent system resulted in a decreased R_coil, the increase in K_m and c*. The higher effective diffusion coefficient of drug calculated by using the Crank's diffusion model was observed in the polymer matrix prepared at an acetone-to-methanol molar ratio of 69:31. The PCA models indicated that the drug surface enrichment and the K_m were directly proportional to the drug burst release, while the entanglement index was inversely correlated. Further, the particle size had a less significant impact on the drug burst release. This study implies that the polymer molecular behavior would influence the microscopic connectivity and diffusivity of polymer matrix, which eventually affects the drug release kinetics.