The effect of polyoxyethylene polymers on the transport of ranitidine in Caco-2 cell monolayers

The phenomenon of physical ageing or structural relaxation and its effect on the performance of dexamethasone loaded poly(lactide-co-glycolide) (PLGA) microspheres was evaluated. Microspheres were incubated at temperatures (-20 (control), 4 and 25°C) below their glass transition temperature for 12 months. Physical ageing occurred in microspheres incubated at 25°C due to structural relaxation of the polymer chains which occurs to achieve a lower equilibrium energy state. Significant physical ageing was not observed in microspheres incubated at 4°C due to the lower molecular mobility of PLGA. The rate of structural relaxation (at 25°C) was a function of free volume which decreased with time. The microspheres incubated at 25°C for 12 months resulted in a slower release profile after day 25 when compared to the control microspheres. This was speculated to be due to a reduction in free volume upon physical ageing which in turn may reduce water absorption and retention of acidic degradation products in the PLGA matrix, hence reducing the degradation rate of PLGA. Therefore, exposure to ambient temperature during storage, shipping or handling may cause physical ageing in PLGA microspheres and hence, their performance may be affected. Storage temperatures of 4°C or lower may be considered appropriate for PLGA microspheres.     

Effect of thermal history on the glassy state of indapamide

The effects of thermal history, e.g. cooling rate, annealing, etc., on the thermal behaviour of indapamide glass were determined by differential scanning calorimetry (DSC). The glass was prepared by heating indapamide crystals (m.p. 162 degrees C) to 180 degrees C, and then cooling the melt to room temperature. The glass transition temperature (Tg) of the material was 98 degrees C. An endotherm, due to thermal relaxation of the glass, was observed in the DSC thermogram when indapamide glass was prepared by slow cooling or was annealed isothermally at a temperature below Tg. Such enthalpy relaxation may be observed during ageing of pharmaceutical glasses and might influence their physico-chemical properties.     

Pharmaceutical and immunological evaluation of a single-shot hepatitis B vaccine formulated with PLGA microspheres

A single-shot Hepatitis B vaccine formulation using poly(d,l)-lactide-co-glycolide acid (PLGA) microspheres as a delivery system was examined using a variety of biophysical and biochemical techniques as well as immunological evaluation in C3H mice. PLGA microsphere encapsulation of the Hepatitis B surface antigen (HBsAg), a lipoprotein particle, resulted in good recoveries of protein mass, protein particle conformational integrity, and in vitro antigenicity. Some partial delipidation of the HBsAg, however, was observed. The loading and encapsulation efficiency of HBsAg into the PLGA microspheres were measured along with the morphology and size distribution of the vaccine-loaded PLGA microspheres. The in vitro release kinetics of HBsAg from the PLGA microspheres was evaluated and found to be affected by experimental conditions such as stirring rate. HBsAg showed enhanced storage stability at 37 degrees C in the slightly acidic pH range reported to be found inside PLGA microspheres; thus, the antigen is relatively stable under conditions of temperature and pH that may mimic in vivo conditions. The immunogenicity of the microsphere formulations of HBsAg was compared with conventional aluminum adjuvant formulated HBsAg vaccine in C3H mice. Comparisons were made between aluminum formulations (one and two injections), PLGA microsphere formulations (single injection), and a mixture of aluminum and PLGA microsphere formulations (single injection). The nine-month serum antibody titers indicate that a single injection of a mixture of aluminum and PLGA-formulated HBsAg results in equal or better immune responses than two injections of aluminum-formulated HBsAg vaccine. Based on these in vitro and in vivo studies, it is concluded that HBsAg can be successfully encapsulated and recovered from the PLGA microspheres and a mixture of aluminum-adjuvanted and PLGA-formulated HBsAg can auto-boost an immune response in manner comparable to multiple injections of an aluminum-formulated vaccine.     

Stability prediction of amorphous benzodiazepines by calculation of the mean relaxation time constant using the Williams-Watts decay function.

The enthalpic relaxation of three amorphous benzodiazepines, diazepam, temazepam and triazolam was studied using differential scanning calorimetry for ageing temperatures which were below the glass transition temperature, and ageing times up to 16 h. Experimental determination of the relaxation enthalpy and the heat capacity change, both accompanying the glass transition, enabled us to calculate the extent of relaxation of the amorphous drugs at specific ageing conditions. Fitting of the relaxation function to the Williams-Watts two parameter decay function led to calculation of the mean relaxation time constant tau and the molecular relaxation time distribution parameter beta. The mean relaxation time constants for the three drugs increased from approximately ten h at the glass transition temperature with more than eight orders of magnitude at 66 K below the glass transition temperature. It was found that the benzodiazepines exhibited significant molecular mobility until approximately 50 K below the glass transition temperature; below this temperature molecular mobility becomes unimportant with respect to the shelf life stability. Hence the presented procedure provides the formulation scientist with a tool to set storage conditions for amorphous drugs and glassy pharmaceutical products.     

Molecular Mobility of Amorphous Pharmaceutical Solids Below Their Glass Transition Temperatures

Purpose. To measure the molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures (Tg), using indomethacin, poly (vinyl pyrrolidone) (PVP) and sucrose as model compounds. Methods. Differential scanning calorimetry (DSC) was used to measure enthalpic relaxation of the amorphous samples after storage at temperatures 16-47 K below Tg for various time periods. The measured enthalpy changes were used to calculate molecular relaxation time parameters. Analogous changes in specimen dimensions were measured for PVP films using thermomechanical analysis. Results. For all the model materials it was necessary to cool to at least 50 K below the experimental Tg before the molecular motions detected by DSC could be considered to be negligible over the lifetime of a typical pharmaceutical product. In each case the temperature dependence of the molecular motions below Tg was less than that typically reported above Tg and was rapidly changing. Conclusions. In the temperature range studied the model amorphous solids were in a transition zone between regions of very high molecular mobility above Tg and very low molecular mobility much further below Tg. In general glassy pharmaceutical solids should be expected to experience significant molecular mobility at temperatures up to fifty degrees below their glass transition temperature.     

Influence of storage temperature and moisture on the performance of microsphere/hydrogel composites

The current study involved investigation of the effect of storage temperature and moisture on the performance of poly(lactide-co-glycolide) (PLGA) microsphere/poly(vinyl-alcohol) (PVA) hydrogel composites. Physical aging occurred in composites stored at 25 °C due to structural relaxation. The glass transition temperature (Tg) and enthalpy of relaxation of the composites increased leading to a slower cumulative % release. The Tg of composites incubated at 40 °C, 75% RH decreased significantly due to the plasticization effect of absorbed water, whereas no change was observed in the Tg of microspheres alone; indicating that the hydrogel component enhanced water absorption. PLGA degradation occurred leading to significantly faster dexamethasone release following incubation at 40 °C, 75% RH for 1 month. No significant change was observed in the in vitro release profiles of composites after 6 months storage at 25 °C, 60% RH, however, release was accelerated following 12 months storage. Accordingly, exposure of the composites to ambient temperature/moisture during storage, shipping or handling may cause physical aging, plasticization, and degradation and hence, their performance may be affected. The extent to which the performance of the composite is affected by storage temperature and moisture is a net effect of physical aging and moisture induced plasticization/hydrolytic degradation.     

A novel approach to stabilization of protein drugs in poly(lactic-co-glycolic acid) microspheres using agarose hydrogel

A novel approach has been taken to stabilize protein drugs in poly(lactic-co-glycolic acid) (PLGA) microspheres. This approach creates a new protein drug delivery system, which is based on the combination of agarose hydrogel particles and PLGA microspheres. This combination produces a heterogeneously structured polymeric composite. The protein drug molecules are encapsulated in the agarose hydrogel particles and the drug-containing agarose hydrogel particles are further dispersed in the PLGA microspheres. One PLGA microsphere may contain many agarose hydrogel particles to form a PLGA–agarose composite microsphere. The PLGA–agarose composite microspheres have spherical shape and a smooth surface. They possess a normal or Gaussian size distribution and an average diameter of 150 μm. The PLGA–agarose composite microspheres have higher protein loading efficiency than that of the conventional PLGA microspheres. The hydration of the PLGA–agarose composite microsphere matrix is faster than that of the conventional PLGA microspheres. Protein drugs can be slowly released from the PLGA–agarose composite microspheres. The agarose hydrogel particles can stabilize protein drugs in the PLGA matrix, which is the major advantage of this novel protein drug delivery system over the conventional PLGA microspheres.     

Conformational stability of a model protein (bovine serum albumin) during primary emulsification process of PLGA microspheres synthesis

The goal of this study was to investigate the conformational stability of a model protein, bovine serum albumin (BSA), during the primary emulsification process of poly(D,L-lactide-co-glycolide) (PLGA) microspheres preparation. Differential scanning calorimeter (DSC) was utilized to assess the conformational structure of BSA during primary emulsification in the presence and absence of PLGA. Three excipients [i.e. mannitol, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sodium dodecyl sulfate (SDS)] were investigated for their stabilizing effect on BSA during emulsification process. The DSC profile of intact BSA was best fitted by a non-2-state model with two peaks, which have midpoint temperatures (T(m1), 60.9 +/- 0.4 degrees C and T(m2), 66.4 +/- 1.0 degrees C), respectively, and a total calorimetric enthalpy Delta H(tot) of 599 +/- 42 kJ/mol. After emulsifying BSA aqueous solution with methylene chloride, an additional apparent peak at a higher temperature was observed. The T(m) of this peak was 77.4 +/- 0.8 degrees C. HP-beta-CD was able to suppress the occurrence of an additional peak, whereas mannitol failed. SDS increased the thermal stability of BSA dramatically. Furthermore, HP-beta-CD increased BSA recovery from 72 +/- 8% to 89 +/- 7% after extraction from w/o in the presence of PLGA. These results provided evidence that HP-beta-CD could be a promising excipient for conformational stability of BSA during synthesis of PLGA microspheres.     

Influence of irradiation sterilization on poly(lactide-co-glycolide) microspheres containing anti-inflammatory drugs

Gamma-irradiation is finding increasing use in the sterilization of pharmaceutical products. However, irradiation might also affect the performance of drug delivery systems. In this study, the influence of gamma-irradiation on the physicochemical properties of two commonly used non-steroidal anti-inflammatory drugs (NSAIDs) [naproxen sodium (NS) and diclofenac sodium (DS)] was investigated. The drugs were incorporated in poly(lactide-co-glycolide) (PLGA, 50:50; molecular weight 34000 or 88000 Da) microspheres. The biodegradable microspheres were irradiated at doses of 5, 15, 25 kGy using a 60Co source. Drug loading of irradiated and non-irradiated microspheres with both 34000 and 88000 Da polymers were essentially the same. A significant difference was noticed in the particle sizes of the irradiated as compared to the non-irradiated formulations. Notably, in release studies, the amount of active substance released from PLGA microspheres showed an increase with increasing irradiation dose. In DSC, the glass transition temperatures (Tg) of microspheres exhibited a slow increase with irradiation dose.     

The effect of different grades of PLGA on characteristics of microspheres encapsulated with cyclosporine A

The aim of this study was to evaluate the effect of different grades of poly D, L lactide-co-glycolide (PLGA) on the properties of microspheres encapsulated with Cyclosporine A (CyA). Microspheres were prepared by solvent evaporation method using three grades of PLGA. Various characteristics of microspheres such as morphology, size distribution, encapsulation efficiency and release profile were evaluated. Complementary studies were also carried out by Infrared (IR) spectroscopy and Differential scanning calorimetry (DSC) to evaluate possible drug-polymer interactions. Scanning electron microscopy (SEM) studies showed microspheres as spherical particles with CyA deposited as islands on the surface of spheres. Particle size range was 1-25 microm for microspheres made of PLGA (50:50) which showed the minimum size. Encapsulation efficiency was found to vary from 75% to 92% in various formulations. The profile of release was biphasic, showing an initial rapid phase followed by a continuous and slower rate thereafter. Microspheres made of grades 50:50 and 85:15 showed the highest and lowest amount of drug release, respectively. IR spectra for drug, polymer and microspheres did not indicate any chemical interaction between the components of microsphere and DSC thermograms revealed that CyA was present in its amorphous state within microspheres. In conclusion, the effect of polymer characteristics should be considered in microsphere formulations. In this study, suitable microspheres especially with PLGA (50:50) were prepared which allow the controlled release of CyA over a prolonged period of time.     

Direct Observation of the Enthalpy Relaxation and the Recovery Processes of Maltose-Based Amorphous Formulation by Isothermal Microcalorimetry

Purpose. The applicability of isothermal microcalorimetry (IMC) for evaluating enthalpy relaxation and recovery processes of amorphous material was assessed. Methods. A maltose-based formulation was prepared by freeze-dry method. Differential scanning calorimetry (DSC) was used to investigate its glass transition and relaxation behaviors. IMC was applied to quantitatively analyze the relaxation and the recovery processes. The IMC data were analyzed using a derivative of the Kohlrausch-Williams-Watts equation. Results. The glass transition temperature of the formulation and its fictive temperature stored at 15°C for 1 year were 62 and 32°C, respectively. DSC study showed that annealing below the fictive temperature increased the enthalpy recovery, but it was decreased by annealing at higher temperatures. IMC enabled direct observation of the heat flow during both the relaxation and the recovery processes. The decay constant for the recovery process (recovery time) was much smaller and less sensitive to the temperature than that for the relaxation process (relaxation time). Conclusions. IMC was successfully used to obtain quantitative information on both relaxation and recovery processes of amorphous material. The relaxation parameters obtained by this method could explain the thermodynamic behavior of the formulation.     

Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers

Microspheres were prepared from poly(L-lactic acid) polymers having molecular weights between 500 and 50k g/mol. The polymers were synthesized using two initiator molecules, L-lactic acid oligomer (PLLA-LA) or stearyl alcohol (PLLA-SA). For both PLLA-LA and PLLA-SA polymers, glass (Tg) and melting (Tm) transition temperatures and enthalpy of melting all increased as the polymer molecular weight increased. PLLA-SA showed the greatest change in Tg (-13 to 54 degrees C) as molecular weight increased from 500 to 10k x g/mol, compared to 25 to 55 degrees C for PLLA-LA polymers. Changes in Tm and enthalpy of melting with increasing molecular weight were similar for both PLLA-LA and PLLA-SA. Paclitaxel release from 30% paclitaxel loaded microspheres in the size range of 50-90 microm was affected by these changes in polymer properties as molecular weight increased. As the molecular weight increased from 2k to 50k x g/mol the amount of drug released from microspheres over 14 days decreased from 76 to 11% of the initial drug load. The release profiles were consistent with a diffusion controlled mechanism provided a two-compartment model was employed. According to this model, the total amount of 'available' drug (compartment 1) was released by diffusion in 14 days while the remainder (compartment 2) was confined within the polymeric matrix and could not diffuse out at a measurable rate. Following the in vitro release study, microsphere made from 2k-10k g/mol polymers showed significant signs of disintegration whereas 50k x g/mol polymer microspheres remained intact.     

PLGA-PEG microspheres of teverelix: influence of polymer type on microsphere characteristics and on teverelix in vitro release

Teverelix microspheres were produced by coacervation using a new type of poly(ester-carbonates) made of block copolymers of poly(lactic-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Five different PLGA-PEG copolymers and one PLGA were used. The 'stability window' has been determined for all polymers. It varied depending on the molecular weight and the weight percentage of PEG. With increasing core loading (from 9.4 to 34.2%), the microparticle size increased from 10-50 to 5-1000 micrometer. The core loading did not have any influence on encapsulation yield, which remained above 80%. The influence of polymer type on microsphere characteristics was studied at two different core loadings: 9.4 and 28%. At a low core loading, the nature of the polymer had no influence on microsphere characteristics whereas at 28%, only PLGA-PEG copolymers gave acceptable microparticles in term of particle size. At 28%, the glass transition temperature (T(g)) of loaded particles was 1-8 degrees C higher than the T(g) of the corresponding polymer. Increasing the core loading increased teverelix release whereas polymer degradation was decreased. All microparticles made of PLGA-PEG copolymers showed a faster release of teverelix than PLGA-based microspheres, whatever the core loading. One PLGA-PEG was selected on the basis of in vitro release rate for further in vivo investigations.     

Relationship between the crystallization rates of amorphous nifedipine, phenobarbital, and flopropione, and their molecular mobility as measured by their enthalpy relaxation and (1)H NMR relaxation times

Isothermal crystallization of amorphous nifedipine, phenobarbital, and flopropione was studied at temperatures above and below their glass transition temperatures (T(g)). A sharp decrease in the crystallization rate with decreasing temperature was observed for phenobarbital and flopropione, such that no crystallization was observed at temperatures 20-30 degrees C lower than their T(g) within ordinary experimental time periods. In contrast, the crystallization rate of nifedipine decreased moderately with decreasing temperature, and considerable crystallization was observed at 40 degrees C below its T(g) within 4 months. The molecular mobility of these amorphous drugs was assessed by enthalpy relaxation and (1)H-NMR relaxation measurements. The enthalpy relaxation time of nifedipine was smaller than that of phenobarbital or flopropinone at the same T - T(g) values, suggesting higher molecular mobility of nifedipine. The spin-lattice relaxation time in the rotating frame (T(1rho)) decreased markedly at temperature above T(g). The slope of the Arrhenius type plot of the T(1rho) for nifedipine protons changed at about 10 degrees C below the T(g), whereas the slope for phenobarbital protons became discontinuous at about 10 degrees C above the T(g). Even at temperatures below its T(g), the spin-spin relaxation process of nifedipine could be described by the sum of its Gaussian relaxation, which is characteristic of solid protons, and its Lorentzian relaxation, which is characteristic of protons with higher mobility. In contrast, no Lorentzian relaxation was observed for phenobarbital or flopropione at temperatures below their T(g). These results also suggest that nifedipine has higher molecular mobility than phenobarbital and flopropione at temperatures below T(g). The faster crystallization of nifedipine than that of phenobarbital or flopropione observed at temperatures below its T(g) may be partly ascribed to its higher molecular mobility at these temperatures.     

The characterization of paclitaxel-loaded microspheres manufactured from blends of poly(lactic-co-glycolic acid) (PLGA) and low molecular weight diblock copolymers

Paclitaxel-loaded biodegradable drug delivery systems manufactured from poly(lactic-co-glycolic acid) (PLGA) are known to release the drug at extremely slow rates. The objective of this study was to characterize paclitaxel-loaded microspheres composed of blends of PLGA with low molecular weight ampipathic diblock copolymers. The encapsulation and release of a series of poly(epsilon-caprolactone) (PCL)- or poly(D,L-lactic acid) (PDLLA)-co-methoxypolyethylene glycol (MePEG) diblock copolymers was measured using quantitative gel permeation chromatography. Polymeric miscibility was determined by glass transition temperature measurements using differential scanning calorimetry and paclitaxel release was measured using HPLC methods. The PCL- and PDLLA-based diblock copolymers encapsulated at high efficiency and were miscible in PLGA microspheres (30-120m microm size range). The burst phase of paclitaxel release was increased up to 20-fold by the inclusion of diblock copolymers in PLGA microspheres. Approximately 10% of the more hydrophobic PCL-based copolymers released from the microspheres in a short burst over 3 days followed by very slow release over the following 10 weeks. Only the PDLLA-based copolymer released from the PLGA microspheres in a controlled manner over 10 weeks. All microspheres containing PEG were found to have more hydrophilic surfaces (as measured by contact angle) with improved biocompatibility (reduced neutrophil activation) compared to PLGA only microspheres. These results indicate that low molecular weight polyester-based diblock copolymers may be effectively encapsulated in PLGA microspheres to increase paclitaxel release (probably through a micellization process) and improve biocompatibility.     

A short-term (accelerated release) approach to evaluate peptide release from PLGA depot formulations

An accelerated method to evaluate peptide release from poly(dl-lactide-co-glycolide) (PLGA) depot formulations in short time is described. Peptide-loaded microspheres were made from hydrophilic 50∶50 PLGA by a dispersionsolyent extraction technique, and peptide release was studied at 37°C and at higher temperatures in various media. For all accelerated conditions, release was faster at temperatures above the glass transition, Tg, of the host polymer. Complete release of peptide from 8600 MW PLGA was achieved in 35 hours at 50°C in buffered and nonbuffered media containing 0.5% polyvinyl alcohol (PVA). Type of release media and concentration of PVA influenced the release profiles. A PVA concentration of 0.1 to 0.5% was found to prevent aggregation of microspheres at higher temperatures, with an increase in release at the higher PVA concentration. Peptide release was associated with a reduction of pH of the releasing media and increased mass loss. Complete peptide release at pH 4 from 8.6 kd and 28 kd PLGA at 50 and 60°C occurred within 30–40 hours and correlated well with the real-time release at 37°C and pH 7.0. At the higher molecular weight, a slightly longer accelerated release time and higher temperature were required to correlate with the real-time release. The data suggest that by optimization of release conditions such as temperature, surfactant concentration, buffer component, and pH, an accelerated study could be employed to evaluate depot formulations for a given polymer type.     

Characterization of ciclosporin A loaded poly (D,L lactide-co-glycolide) microspheres using modulated temperature differential scanning calorimetry

The aim of this study was to investigate the physical structure of poly (D,L lactide-co-glycolide) (PLGA) microspheres loaded with ciclosporin A in terms of the amorphous properties of the individual components and the phase separation characteristics of the binary systems. Microspheres were prepared using a standard oil-in-water emulsion technique. The thermal properties of the PLGA, ciclosporin A and loaded spheres were investigated using modulated temperature differential scanning calorimetry (MTDSC) using a TA Instruments MTDSC 2920, with scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and high-performance liquid chromatography used as supportive techniques. MTDSC indicated a glass transition for ciclosporin A in the reversing heat flow signal at 107 degrees C, supported by temperature cycling studies, while XRD showed clear evidence for diffraction peaks, thereby indicating that the material as received is semi-crystalline. The unloaded PLGA spheres showed a glass transition (Tg) at 43 degrees C, with no reduction in Tg being observed on loading the peptide up to 50%, w/w. Similarly, no evidence for diffraction peaks were seen for the drug-loaded systems, although the glass transition corresponding to the peptide was observed for the loaded microspheres, suggesting that the drug is present as a separate amorphous phase. Similarly, SEM studies showed the appearance of distinct "islands" on the surface of the spheres that are suggested to correspond to the drug phase, with the size of the islands increasing with drug loading. Evidence is therefore presented that ciclosporin A may exist in a range of solid states, with the degree of crystallinity being altered by processing. In addition, there appears to be little or no miscibility between the drug and PLGA using the manufacturing protocol employed here. These findings may have implications for the choice of manufacturing protocol, the release of peptide drugs from PLGA microspheres and the chemical and physical stability of such drugs.     

Effect of PLGA hydrophilia on the drug release and the hypoglucemic activity of different insulin-loaded PLGA microspheres

The effects of viscosity and hydrophilic characteristics of different PLGA polymers on the microencapsulation of insulin have been studied in?vitro and in?vivo after subcutaneous administration to hyperglycemic rats. Hydrophilic PLGA polymers produced a higher burst effect than the hydrophobic ones. Moreover, an incomplete insulin release was observed with the hydrophilic PLGA polymers in comparison with the hydrophobic ones. An explanation for that incomplete release can be the development of polymer-insulin interactions associated to the polymer hydrophilic/hydrophobic character, as detected by DSC analysis. Differences in the release rate of microsphere formulations lead to differences in the hypoglycemic action and the weight of animals. Hydrophobic PLGA was able to prolong the hypoglycemic action up to 4 weeks which is at least double than that obtained with hydrophilic PLGA of a similar viscosity. Comparing insulin microspheres with an immediate release formulation, microspheres can increase insulin relative bioavailability up to four times.     

Preparation of polysulfone hollow microspheres encapsulating DNA and their functional utilization

Polysulfone hollow microspheres encapsulating DNA were prepared using a liquid-liquid phase separation technique. The microspheres were then used to absorb a DNA-binding intercalating material--ethidium bromide. The amount of DNA encapsulated in the microspheres depended on the concentration of the DNA solution used to prepare the microspheres, and the microsphere morphology depended on both the polymer concentration and the preparation conditions. The amount of ethidium bromide in the microspheres depended mainly on the amount of encapsulated DNA, and the microsphere morphology also affected the removal of the ethidium bromide. The new method of DNA encapsulation is proposed, and the microspheres encapsulating the DNA have the potential to be used in environmental applications.     

聚乳酸-羟基乙酸共聚物载药微球性质及缓释行为的影响因素

聚乳酸-羟基乙酸共聚物（PLGA）包裹药物制成缓释微球是药物缓释方向的研究热点,PLGA微球作为载体,具有良好的生物相容性和降解性,但载药微球的性质和释药性能易受很多因素影响,如PLGA相对分子质量,LA/GA比例,微球制备工艺等,这些因素对载药体系在生物医学领域的应用造成一定限制。结合国内外相关文献,本文综述了PLGA微球在制备及释药过程中,影响其理化性质和重要性能的因素,包括载药量,包封率,突释问题等方面,为PLGA微球进一步研究和优化提供思路。