Microsphere Drug Delivery Systems Research Articles

Nanomicrosphere sustained-release urokinase systems with antioxidant properties for deep vein thrombosis therapy.

Deep vein thrombosis (DVT) is a venous return disorder caused by abnormal clotting of blood in deep veins. After thrombosis, most of the thrombus will spread to the deep vein trunk throughout the limb. If DVT is not treated in time, most of them will develop into thrombosis sequelae and even threaten life. Intravenous thrombolytic drugs are the most promising strategy for treating DVT, but current drugs used for thrombolysis suffer from short half-lives and narrow therapeutic indexes. To effectively manage DVT, it is necessary to develop a novel multifunctional drug-loading system to effectively prolong the treatment time and improve the therapeutic efficacy. In this study, a urokinase-loaded protocatechuic aldehyde-modified chitosan microsphere drug-loading platform was constructed for the treatment of DVT. This microsphere adsorbed urokinase well through electrostatic interaction, and the introduction of bovine serum albumin conferred stability to the microspheres. Therefore, the microsphere drug delivery system could achieve slow drug release to effectively dissolve blood fibrin. In addition, chitosan grafted with protocatechuic aldehyde imparted excellent antioxidant activity to the system to reduce free radicals in the blood vessels. Effective management of oxidative stress could avoid abnormal platelet activation and new thrombus formation. The experimental results showed that this microsphere had good biocompatibility, anti-inflammatory properties, and considerable thrombolytic activity. In conclusion, this study provided a new direction and developed a novel multi-functional nano microsphere drug delivery platform for the treatment of DVT.

Recent advances in polymeric microparticle-based drug delivery systems for knee osteoarthritis treatment.

Due to the poor bioavailability and high joint clearance of drugs, sustained delivery of therapeutic agents has proven difficult in the treatment of osteoarthritis (OA). Intra-articular (IA) drug delivery strategy is an attractive option for enhancing OA patients' prognosis, for which various polymer materials have been used as drug carriers due to their attractive delivery properties, to slow or even reverse the progress of OA by prolonging the duration of therapeutic agent residence in the joint. This article focuses on the recent developments in natural and synthetic polymer-based microsphere drug delivery systems for treating knee osteoarthritis. It evaluates the translational potential of some novel formulations for clinical application.

Immunized Microspheres Engineered Hydrogel Membrane for Reprogramming Macrophage and Mucosal Repair.

The "double-edged sword" effect of macrophages under the influence of different microenvironments determines the outcome and prognosis of tissue injury. Accurate and stable reprogramming macrophages (Mφ) are the key to rapid wound healing. In this study, an immunized microsphere-engineered GelMA hydrogel membrane is constructed for oral mucosa treatment. The nanoporous poly(lactide-co-glycolide) (PLGA) microsphere drug delivery system combined with the photo-cross-linkable hydrogel is used to release the soybean lecithin (SL)and IL-4 complexes (SL/IL-4) sustainedly. In this way, it is realized effective wound fit, improvement of drug encapsulation, and stable triphasic release of interleukin-4 (IL-4). In both in vivo and in vitro experiments, it is demonstrated that the hydrogel membrane can reprogram macrophages in the microenvironment into M2Mφ anti-inflammatory types, thereby inhibiting the local excessive inflammatory response. Meanwhile, high levels of platelet-derived growth factor (PDGF) secreted by M2Mφ macrophages enhanced neovascular maturation by 5.7-fold, which assisted in achieving rapid healing of oral mucosa. These findings suggest that the immuno-engineered hydrogel membrane system can re-modulating the biological effects of Mφ, and potentiating the maturation of neovascularization, ultimately achieving the rapid repair of mucosal tissue. This new strategy is expected to be a safe and promising immunomodulatory biomimetic material for clinical translation.

A Review on Microsphere

The microsphere is having free-flowing powder properties that are incorporate proteins and synthetic or natural polymer. This polymer is biodegradable in nature and particle size having less than 200 µm. Advanced drug delivery system has various advantages over the mainstream multi dose therapy. The microsphere's drug delivery systems are acceptable for attained delay or sustained release formulation with minimum risk of dose repeatability and small gastric habitation time. The present review provides a complete discussion of therapeutic aspects of the microsphere drug delivery system into deliberation of the required area for microparticulate, types of polymers used, method of preparation, type of microspheres in detail, parameters & targeting of microspheres & practical aspects of microspheres.
 Keywords: Microspheres, bioavailability, types, classification, ideal properties, evaluation, etc.

Microsphere: A Unique and Useful Drug Delivery System

Microsphere is one the novel technology that is used to deliver the drug to it targeted site. Microsphere they are micro particle in size. They are of natural and synthetic one. There are various approaches in delivering a therapeutic substance to the target site in a sustained controlled release fashion. For preparation of microsphere protein physiochemical property to be optimized this include optimal pH, protein stochiometry and protein concentration. Some of the important microsphere technology includes Ceformin microsphere technology Ceformin EI, Ceformin TI, Ceformin EA/CR, Silk microsphere and gelatin microsphere. Microsphere drug delivery system has gained enormous attention due to its wide range of application as it covers targeting the drug to particular site to imaging and helping the diagnostic features. Microsphere is excellent polymer used for buccal delivery. It is also used to deliver pacilitaxel at the tumor site. In the present study valuable and selective information on microsphere is enlightened with its important applications which will be beneficial for further newer drug development.

Microsphere: A Unique and Useful Drug Delivery System

Microsphere is one the novel technology that is used to deliver the drug to it targeted site. Microsphere they are micro particle in size. They are of natural and synthetic one. There are various approaches in delivering a therapeutic substance to the target site in a sustained controlled release fashion. For preparation of microsphere protein physiochemical property to be optimized this include optimal pH, protein stochiometry and protein concentration. Some of the important microsphere technology includes Ceformin microsphere technology Ceformin EI, Ceformin TI, Ceformin EA/CR, Silk microsphere and gelatin microsphere. Microsphere drug delivery system has gained enormous attention due to its wide range of application as it covers targeting the drug to particular site to imaging and helping the diagnostic features. Microsphere is excellent polymer used for buccal delivery. It is also used to deliver pacilitaxel at the tumor site. In the present study valuable and selective information on microsphere is enlightened with its important applications which will be beneficial for further newer drug development.

Abstract 1325: Oral delivery of drug-loaded microspheres for cancer

Abstract The oral route remains the preferred method of administering drugs; however, this delivery mode faces many challenges, including low bioavailability of the administered drug, generalized toxicity and drug decomposition. Microsphere drug delivery systems have evolved to improve patient compliance, reduce toxicity, and increase efficacy. Additionally, the use of microspheres to deliver drugs has many other advantages, such as control-release of the active drug, increase bioavailability and target delivery of the drug to the desired tissue/cell. Our research explored the utility of encapsulating vorinostat in biodegradable microsphere delivery system, to be delivered orally via a capsule, to attain effective therapeutic effect. The strategy is to develop an oral, biodegradable albumin-based microsphere delivery system containing vorinostat that would elicit targeted inhibitory effect on cancer to enhance therapeutic efficacy. Vorinostat-loaded microspheres were prepared by a microencapsulation method through spray drying. The parameters for spray drying were optimized to find the best formulation for enhanced uptake and efficacy in vitro in cultured HEPG2 cells. Microspheres were loaded into capsules. Microspheres and capsule formulations were assessed for particle size, particle size distribution, surface morphology and properties and Zeta potential measurements. Drug release characteristics were quantified using dissolution studies. Chemical and thermal stability of the encapsulated drug and microsphere formulations were evaluated using FTIR and DSC, respectively. The uptake and cellular internalization of the microspheres were evaluated using co-cultures of Caco-2 cells and Raji cells. In vitro cytotoxicity was evaluated using MTT and clonogenic assays. Histone deacetylase (HDAC) activity levels in cells from treatment of free vorinostat and microparticle formulation were compared. Global histone modifications in HEPG2 cancer cells due to vorinostat-loaded microsphere treatment were also analyzed. Our data indicated that vorinostat microspheres were 1-2 microns in size and possessed spherical morphology. Zeta potential measurements show values of -30 mV, which indicated colloidal stability of the microsphere dispersion. Uptake studies indicated that more than 50% of the microspheres were internalized inside the cells within 12 hours. Additionally, dissolution studies showed that within 24 hours, 80% of the drug is sustained-release from the microsphere formulations. HDAC activity levels were shown to be decreased in cultured cells when vorinostat microspheres were used. Our in vitro studies showed that drug-loaded microsphere formulations exert cytotoxic effects on cultured cells. In summary, microspheres were shown to be a potential effective oral delivery system to administer anticancer drugs, with enhanced efficacy due to their controlled-release manner. Citation Format: Duc P. Do. Oral delivery of drug-loaded microspheres for cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1325.

Preparation and drug release properties of norisoboldine-loaded chitosan microspheres

This study aimed to develop injectable norisoboldine (NOR) chitosan microspheres formulated through the emulsion cross-linking method. The formulation was optimized using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The morphology, size, physicochemical characterization and in vitro release behavior of the optimized formulation were evaluated. Scanning electron micrographs (SEM) indicated that the microspheres were spherical with a smooth surface. The encapsulation efficiency and drug loading content of the microspheres were 38.89%±1.72% and 4.25%±0.15%, respectively, with an average size of 105μm. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed the absence of a drug-polymer interaction and the amorphous nature of an entrapped drug. Analysis results of drug release in vitro show the burst release of the microsphere in 2h and a slow progression afterward. In vivo studies using Sprague-Dawley rats revealed that the NOR-loaded chitosan microspheres were biocompatible. This study suggests that the BBD with desired formulation could provide a suitable drug delivery system of chitosan microspheres.

Enhanced Degradation of Lactide-co-Glycolide Polymer with Basic Nucleophilic Drugs

The purpose of this study was to examine the degradative effect of weakly basic nucleophilic drugs on a lactide-co-glycolide (PLGA) polymer in a microsphere formulation. Biodegradable PLGA microspheres of two second-generation atypical antipsychotics, Risperidone and Olanzapine, were manufactured using a solvent extraction/evaporation technique. The effect of drug content, buffer pH and temperature on polymer molecular weight and degradation, were examined via a series of experiments and compared against a control (Placebo PLGA microspheres). In comparison to Placebo microspheres, significant polymer molecular weight reduction was observed upon encapsulation of varying levels of either Risperidone or Olanzapine. There was excellent correlation between the extent of molecular weight reduction during manufacture and the amount of encapsulated drug in the microspheres. Subsequent studies on polymer degradation showed: the following (a) the Placebo and Olanzapine microspheres followed pseudo first order kinetics, (b) Risperidone microspheres exhibited biphasic degradation profiles, and (c) polymer degradation was dependent on temperature, not pH. The findings of these studies show that encapsulation of weakly basic nucleophile type drugs into PLGA can accelerate the biodegradation of the PLGA and have major implications on the design of polymeric microsphere drug delivery systems.

Porous microspheres of amorphous calcium phosphate: Block copolymer templated microwave-assisted hydrothermal synthesis and application in drug delivery

Amorphous calcium phosphate (ACP) microspheres with a porous and hollow structure have been prepared using an aqueous solution containing CaCl2 as a calcium source, adenosine triphosphate disodium salt (Na2ATP) as a phosphorus source in the presence of a block copolymer methoxyl poly(ethylene glycol)-block-poly(d,l-lactide) (mPEG-PLA) by the microwave-assisted hydrothermal method. The effects of microwave hydrothermal temperature and the concentrations of CaCl2 and Na2ATP on the crystal phase and morphology of the product are investigated. The as-prepared ACP porous hollow microspheres have a relatively high specific surface area of 232.9m2g−1 and an average pore size of 9.9nm. A typical anticancer drug, docetaxel, is used to evaluate the drug loading ability and drug release behavior of ACP porous hollow microspheres in phosphate buffered saline (PBS) with different pH values of 4.5 and 7.4. The experiments reveal that the ACP porous hollow microspheres have a high drug loading capacity and favorable pH-responsive drug release property, and the ACP porous hollow microsphere drug delivery system shows a high ability to damage tumor cells. It is expected that the as-prepared ACP porous hollow microspheres are promising for the applications in various biomedical fields such as drug delivery.

Formulation Development and In vitro Evaluation of Oral Extended release Capsules Containing Biodegradable Microspheres

Oral extended-release delivery of Biopharmaceutics Classification System (BCS) class II and III compounds is desirable in order to decrease dosing frequency and potential adverse effects. Maintaining an extended-release profile of the drug is ideal to minimize fluctuations in plasma concentrations. The main objective of this research was to formulate a polymeric microsphere drug delivery system that will effectively provide extended-release characteristics via an orally administered capsule. Using acetaminophen and ibuprofen as model drugs, this drug delivery system was shown to provide extended-release characteristics of the drug for enhanced efficacy. The biodegradable polymeric matrix was formulated using bovine serum albumin (BSA) with glutaraldehyde as the crosslinker. The drug of interest was then encapsulated into the polymeric matrix and spray-dried into microspheres. Once prepared, the drug-loaded microsphere powder was placed into hard gelatin capsules. The physicochemical properties of the microsphere formulations were characterized. Additionally, differential scanning calorimetry was utilized to examine the thermal stability of the encapsulated drug. Release studies were conducted in vitro to examine the release profile of the drug. Cell uptake studies were carried out to examine the internalization capability of microsphere formulations. Drugloaded microspheres were found to be approximately 2 microns in size and exhibited a uniform size distribution. Zeta potential measurements were shown to be approximately -30 mV, which indicated that the microspheres are stable in dispersions. Release data showed a constant release of the drug from the microsphere and capsule formulations for at least 16 hours. Formulated microspheres were able to be internalized into human intestinal Caco-2 cells. These data provided evidence for the role of the microsphere delivery system in the extended-release delivery of BCS Class II and III drug substances.

Formulation development and evaluation of colonic drug delivery system of budesonide microspheres by using spray drying technique

AimPresent work mainly deals with the formulation of colon targeting dosage form of budesonide, using natural polysaccharides as polymer by utilizing spray drying technique. Budesonide is locally acting corticosteroid utilized for the treatment of inflammatory bowel disease. Budesonide is having high glucocorticoid and low mineralocorticoid effect. MethodsChemical modification of chitosan was carried out by using glutaraldehyde which causes crosslinking between chitosan molecules rendering them water insoluble. Drug, polymer and crosslinking agent were spray dried to form microparticles. 2 ml of 25% glutaraldehyde was found to be necessary for required crosslinking of 1% chitosan in acetic acid. ResultsFormed microparticles showed 20% drug release in initial 5 h and 80% drug release in rat fecal content media which also suggested that specific degradability of chitosan by colonic bacteria remains after crosslinking also. Formed microparticles were then evaluated for various parameters like morphology, particle size distribution, % yield, % entrapment, % of loading and drug release. ConclusionSpray drying produces narrow and small size microparticles of budesonide.

Formulation and evaluation of drug-loaded targeted magnetic microspheres for cancer therapy

Enhanced and targeted drug delivery using biodegradable microspheres is emerging as a promising approach for cancer therapy. The main objective of the present research was to formulate, characterize, and evaluate iron oxide (magnetic) containing a bovine serum albumin-based microsphere drug delivery system, capable of efficiently delivering sulforaphane, a histone deacetylase inhibitor, for an extended period of time in vivo. Magnetic microspheres were prepared by spray-drying and characterized for their physicochemical properties and dissolution profile. Further, they were evaluated for therapeutic efficacy in in vitro and in vivo systems. In vitro studies in B16 melanoma cells revealed that there was about 13%–16% more inhibition of cell viability when either 30 μM or 50 μM of sulforaphane was used with iron oxide in the polymeric carrier. Data from in vivo studies in C57BL/6 mice revealed that the magnetic microspheres (localized to the tumor site with the help of a strong magnet) inhibited 18% more tumor growth as compared with sulforaphane in solution. In addition, there was a 40% reduction in histone deacetylation levels in mice treated with iron oxide microspheres containing sulforaphane. Thus, magnetic microspheres are shown to be an effective drug delivery system for anticancer drugs.

Effect of Dexamethasone-Loaded Poly(Lactic-Co-Glycolic Acid) Microsphere/Poly(Vinyl Alcohol) Hydrogel Composite Coatings on the Basic Characteristics of Implantable Glucose Sensors

Hydrogels alone and in combination with microsphere drug delivery systems are being considered as biocompatible coatings for implantable glucose biosensors to prevent/minimize the foreign body response. Previously, our group has demonstrated that continuous release of dexamethasone from poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composites can successfully prevent foreign body response at the implantation site. The objective of this study was to investigate the effect of this composite coating on sensor functionality. The PLGA microsphere/PVA hydrogel coatings were prepared and applied to glucose biosensors. The swelling properties of the composite coatings and their diffusivity to glucose were evaluated as a function of microsphere loading. Sensor linearity, response time, and sensitivity were also evaluated as a function of coating composition. The PLGA microsphere/PVA hydrogel composite coating did not compromise sensor linearity (sensors were linear up to 30 mM), which is well beyond the physiological glucose range (2 to 22 mM). The sensor response time did increase in the presence of the coating (from 10 to 19 s); however, this response time was still less than the average reported values. Although the sensitivity of the sensors decreased from 73 to 62 nA/mM glucose when the PLGA microsphere loading in the PVA hydrogel changed from 0 to 100 mg/ml, this reduced sensitivity is acceptable for sensor functionality. The changes in sensor response time and sensitivity were due to changes in glucose permeability as a result of the coatings. The embedded PLGA microspheres reduced the fraction of bulk water present in the hydrogel matrix and consequently reduced glucose diffusion. This study demonstrates that the PLGA microsphere/PVA hydrogel composite coatings allow sufficient glucose diffusion and sensor functionality and therefore may be utilized as a smart coating for implantable glucose biosensors to enhance their in vivo functionality.

Gastroretentive drug delivery system of acyclovir-loaded alginate mucoadhesive microspheres: Formulation and evaluation

In the present study, mucoadhesive alginate microspheres of acyclovir were prepared to prolong the gastric residence time using a simple emulsification phase separation technique. The particle size of drug-loaded formulations was measured by SEM and the particle size distribution was determined using an optical microscope and mastersizer. The release profile of acyclovir from microspheres was examined in simulated gastric fluid (SGF pH 1.2). The particles were found to be discreet and spherical with the maximum particles of an average size (70.60 ± 2.44 µm). The results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and decreased with increase in stirring speed. The entrapment efficiency was found to be in the range of 51.42−80.46%. The concentration of the calcium chloride (% w/v) of 10% and drug–polymer ratio of 1:4 resulted in an increase in the entrapment efficiency and the extent of drug release. The optimized alginate microspheres were found to possess good mucoadhesion (66.42 ± 1.01%). The best fit model with the highest regression coefficient values (R2) was predicted by Peppas model (0.9813). In Gamma scintigraphy analysis, the section of GIT was critically analyzed and much differentiation was present at each time point after oral administration, which revealed that the optimized formulation demonstrated gastroretention in vivo for more than 4 h, which revealed that optimized formulation could be a good choice for gastroretentive systems.

Carbohydrate-Modified Siloxane Surfactants and Their Adsorption and Aggregation Behavior in Aqueous Solution

Four carbohydrate-modified siloxane surfactants, Si(n)N-GA and Si(n)N-LA (n = 3, 4), were designed and synthesized. Their surface activities, adsorption, and aggregation behavior in aqueous solution were investigated by surface tension measurements, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to the bulky siloxane moiety at the end of hydrophobic chains, the surfactant solutions displayed low critical aggregation concentration (cac) and low surface tension. Surface tension measurement for all three surfactants are under 22 mN x m(-1), much lower than those of ordinary hydrocarbon surfactants. Due to its poor solubility in water, surface tension of Si(4)N-GA could not be measured. DLS and TEM analysis of Si(3)N-GA, Si(3)N-LA, and Si(4)N-LA aqueous solutions revealed self-assembled spherical vesicles, indicating potential applications as microsphere drug delivery systems and as models of biomembranes.

Risperidone Long-Acting Injection

A long-acting intramuscular formulation of the atypical antipsychotic agent risperidone is now indicated for the maintenance treatment of patients with bipolar I disorder. The formulation utilizes a novel drug delivery system of biodegradable microspheres and is bioequivalent to the oral formulation of the drug. Moreover, fluctuations in plasma drug concentrations at steady state were 1.7-fold lower with long-acting than with oral risperidone. Maintenance treatment with risperidone long-acting injection, as monotherapy in adults with stabilized bipolar I disorder or as an adjunct to standard therapy in adults with stabilized, frequently relapsing bipolar I disorder, was effective in delaying relapse to symptoms in two well designed trials with maintenance phases of 1 or 2 years' duration. The time to relapse to any mood episode (primary endpoint) was significantly longer with risperidone long-acting injection than with placebo in both studies. Risperidone long-acting injection also significantly reduced the risk of relapse relative to placebo in these trials. Maintenance treatment with risperidone long-acting injection was generally well tolerated in patients with bipolar disorder, both as monotherapy and adjunctive therapy, with most adverse reactions being of mild to moderate severity.

Fabrication and drug release properties of poly(5-benzyloxy-trimethylene-co-glycolide) microspheres

Poly(5-benzyloxy-trimethylene carbonate-co-glycolide) random copolymers were synthesized through the ring-opening polymerization of 5-benzyloxy-trimethylene carbonate and glycolide (GA). The copolymers with different compositions, PBG-1 with 17% GA units and PBG-2 with 45% GA units, were obtained. Using these copolymers, microsphere drug delivery systems with submicron sizes were fabricated using an “ultrasonic assisted precipitation method.” The in-vitro drug release from these microspheres was investigated. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Prevention of local tumor growth with paclitaxel-loaded microspheres

Lung cancer is associated with a significant rate of locoregional recurrence after surgical resection, particularly when nonanatomic wedge resections are performed. The primary aim of this study was to assess the feasibility of a microsphere drug delivery system to locally deliver chemotherapy and prevent the establishment and growth of lung cancer cells and establish proof of concept for a potential future approach to target occult microscopic disease remaining at the surgical resection margin. Poly-(D,L-lactic-co-glycolic acid) (PLGA) microspheres loaded with the antineoplastic agent paclitaxel were prepared and tested for antitumor efficacy in an in vitro cell proliferation assay for tumor inhibition and induction of apoptosis. The in vivo prevention of Lewis lung carcinoma cell establishment and growth in subcutaneous tissues of mice was also assessed by comparing 4 treatment groups: Lewis lung carcinoma cells alone, Lewis lung carcinoma cells combined with 100 x 10(6) unloaded (carrier alone) PLGA microspheres, and Lewis lung carcinoma cells combined with 50 x 10(6) or 100 x 10(6) paclitaxel-loaded PLGA microspheres. After the coinjection of Lewis lung carcinoma cells with or without microspheres, in vivo tumor growth was monitored, and tumor weight was recorded on death. Paclitaxel-loaded PLGA microspheres were found to effectively prevent growth of tumor cells in culture through the induction of apoptosis. Similarly, paclitaxel-loaded PLGA microspheres significantly inhibited tumor growth in vivo at both the 50 x 10(6) and 100 x 10(6) microsphere dose (0.497 +/- 0.183 and 0.187 +/- 0.083 g total tumor weight, respectively) compared with 2.91 +/- 0.411 g for Lewis lung carcinoma cells with unloaded microspheres and 3.37 +/- 0.433 g for untreated tumor (P < .001). Toxicity was not clinically apparent in any animal treated with paclitaxel-loaded PLGA microspheres. Paclitaxel-loaded PLGA microspheres induce tumor apoptosis and inhibit the establishment and growth of lung cancer cells both in vitro and in vivo without obvious systemic toxicity. By using models consistent with localized microscopic tumor burdens, these results suggest that local delivery of paclitaxel through a microsphere system might lead to an effective future method of decreasing local tumor recurrence in non-small cell lung cancer when applied to the surgical margins at risk for microscopic tumor foci. Such an approach might be particularly efficacious after wedge resection in the setting of poor pulmonary reserve or significant comorbidity, where local recurrence rates are increased and acceptable alternative treatment options are limited.

Fabrication and in vitro drug release study of microsphere drug delivery systems based on amphiphilic poly-α,β-[ N-(2-hydroxyethyl)- l-aspartamide]- g-poly( l-lactide) graft copolymers

Biodegradable amphiphilic graft copolymers with different compositions were synthesized by grafting poly( l-lactide) (PLLA) sequences onto a water-soluble poly-α,β-[ N-(2-hydroxyethyl)- l-aspartamide] (PHEA) backbone. The critical micelle concentration (CMC) of the graft polymers was determined by fluorescence probe technique. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the graft polymers were proved to have low cytotoxicity. Based on the specific physicochemical property of the graft copolymers, submicron sized microsphere drug delivery systems were prepared by a very convenient “ultrasonic dispersion method”, which did not involve toxic organic solvents. The drug-loaded microspheres had a regular spherical shape with a narrow size distribution. A hydrophobic drug, prednisone acetate, was encapsulated into polymeric microspheres and the in vitro drug release was studied.