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At least 469 records · Page 26Linked to original sources
PubMed2006

Study of the preparation of sustained-release microspheres containing zedoary turmeric oil by the emulsion-solvent-diffusion method and evaluation of the self-emulsification and bioavailability of the oil.

The purpose of this study was to design a sustained-release formulation of an oily drug. The sustained-release microspheres with self-emulsifying capability containing zedoary turmeric oil (ZTO) were prepared by the quasi-emulsion-solvent-diffusion method. The micromeritic properties, the efficiency of emulsification and the drug-release behavior of the resultant microspheres were investigated. The bioavailability of the microspheres was compared with conventional ZTO self-emulsifying formulations for oral administration using 12 healthy rabbits. An HPLC method was employed to determine the concentration of germacrone in plasma, which was used as an index of ZTO. Spherical and compacted microspheres with average diameters of 100-600 microm have been prepared, and their release behavior in distilled water containing 1.2% (w/v) of polysorbate-80 can be controlled by the ratio of polymer/Areosil200 in the microspheres. The resultant emulsions with mean droplet sizes of 200-500 nm are produced when the microspheres are immersed in phosphate buffer (pH 6.8) under gentle agitation. The stability and the droplet size of the resultant emulsions are also affected by the polymer/Areosil200 ratio in the formulation, while the amount of talc has a marked effect on the self-emulsifying rate. The plasma concentration-time profiles with improved sustained-release characteristics were achieved after oral administration of the microspheres with a bioavailability of 135.6% with respect to the conventional self-emulsifying formulation (a good strategy for improving the bioavailability of an oily drug). In conclusion, the sustained-release microspheres with self-emulsifying capability containing ZTO have an improved oral bioavailability. Our study offers an alternative method for designing sustained-release preparations of oily drugs.

Administration, Oral↗
PubMed2004

Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres.

The purpose of our study was to investigate the possibility to microencapsulate liposomes and meningococcal outer membrane vesicles (OMV), both containing neisserial pore protein A (PorA), in biodegradable dextran- and mannan-based microspheres and to study the immunogenicity of the encapsulated PorA formulations. PorA-liposomes and OMV were encapsulated in dextran- or mannan-based microspheres by using an aqueous two-phase system consisting of a polyethylene glycol solution and a methacrylated dextran or mannan solution. The formulations were characterized for size distribution, PorA structure and antigen recovery after release. Calcein-containing model liposomes were used to establish the encapsulation efficiency and release profiles from both types of microspheres. The immunogenicity of the PorA-containing formulations was determined in mice after subcutaneous immunization. Liposomes were encapsulated in dextran and mannan microspheres with a high efficiency (70-90%). Calcein liposomes, after a 5-day lag period, exhibited apparent zero-order release kinetics from both types of microspheres between Days 5 and 10 of incubation in vitro. The total release was 80 and 100% from mannan and dextran microspheres, respectively. The trimeric PorA conformation was preserved in the released liposomes and OMV and the antigen was partly recovered. The immunogenicity of PorA-liposomes and OMV encapsulated in dextran or mannan microspheres was preserved. In conclusion, PorA-liposomes and OMV could be encapsulated in dextran- and mannan-based microspheres with high efficiency. The immunogenicity of encapsulated antigen was preserved.

Animals↗
PubMed2004

Formulation and characterization of Paclitaxel, 5-FU and Paclitaxel + 5-FU microspheres.

The purpose of this study was to compare the combination (Paclitaxel + 5-FU microspheres) with a single drug chemotherapy (Paclitaxel and 5-FU microspheres) against metastatic breast cancer cell line (MDA-MB 435 S). The physicochemical characteristics of the microspheres (i.e. encapsulation efficiency, particle size distribution, in vitro release, thermal characteristics) were studied. The results demonstrated that the encapsulation efficiency of Paclitaxel was high (90%) when the drug was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microparticles with or without 5-fluorouracil (5-FU). However, the encapsulation efficiency of 5-FU was low (19%) and increased to 30% when the drug was encapsulated with Paclitaxel. The mean particle size of microspheres was 2.5microm and were spherical in shape. The in vitro release of both 5-FU and Paclitaxel from the microspheres was relatively fast initially followed by a slower and more controlled release. The cytotoxic activity of Paclitaxel microspheres was far greater compared to either the microspheres containing 5-FU + Paclitaxel or 5-FU alone. Overall results demonstrated that incorporation of Paclitaxel or 5-FU in microspheres enhances the cytotoxicity in more controlled manner compared to that of free drugs and also that careful consideration should be made when combining drugs acting in different phases of cell cycle.

Antineoplastic Agents↗
PubMed2005

Preparation of mucoadhesive microspheres containing antimicrobial agents for eradication of H. pylori.

Mucoadhesive microspheres containing either amoxicillin or clarithromycin were prepared via the interpolymer complexation of poly(acrylic acid) (PAA) with poly(vinyl pyrrolidone) (PVP) and solvent diffusion method. The complexation between the PAA and PVP in an ethanol/water mixture was confirmed by the change in the transmittance of the solution as a function of repeating PAA and PVP unit ratio. The loading efficiency of clarithromycin in the complex microspheres was higher than that of amoxicillin due to the stronger interaction of clarithromycin with the PAA. The microspheres had a spherical shape with a smooth surface and the inside of the microspheres was completely filled. The dissolution rate of the complex microspheres was significantly slower than that of the PVP microspheres, particularly at pH 2.0. Amoxicillin and clarithromycin degraded significantly during the release study at pH 2.0. Therefore, their release rates were corrected using first order degradation rate constants. The amoxicillin release rates were similar regardless of the pH of the medium, while those of clarithromycin differed depending on the pH. The release mechanism of amoxicillin was mainly by a diffusion process and that of clarithromycin was via a dissolution process. The drug release rate from the complex microspheres was significantly lower than that from the PVP microspheres.

Adhesives↗
PubMed2005

New drug salt formation in biodegradable microspheres.

PURPOSE: To investigate the effects of inorganic salts in the external phase of an oil-in-water (O/W) emulsion method during microsphere preparation. METHODS: An O/W emulsion method was used to prepare poly(D,L-lactic acid) microspheres containing quinidine sulfate. Different inorganic salts were used in the external phase during microsphere preparation. Microsphere drug loading was determined by UV and the drug salt anions inside the microspheres were determined by ion chromatography. RESULTS: New drug salts were formed during encapsulation in the microspheres when salts with non-common anions to the drug salt were used. Drug loading increased when NaClO4 or NaSCN were used. The fraction of drug as the new salt in microspheres increased non-linearly with the salt concentration in the external phase, however, the fraction of drug as the new encapsulated salt was linearly related to drug loading. Drug loading decreased and new salt fraction increased with increasing organic solvent volume or with decreasing cosolvent polarity. CONCLUSIONS: Introducing salts containing non-common anions to the drug salt employed in the external phase of O/W emulsion microsphere method leads to new salt formation. The extent of new drug salt formation is affected by salt levels added, cosolvent type and polymer concentration.

Anions↗
PubMed2005

Release of bioactive BMP from dextran-derived microspheres: a novel delivery concept.

Recent developments of biotechnology have produced a great variety of protein and bioactive drugs. For these drugs to be used therapeutically, suitable drug delivery systems have become increasingly essential. Dextran-derived biomaterials have been considered to be compatible matrices for protein and bioactive drugs because of their hydrophilic properties and ability to control drug dissolution and permeability. A novel class of dextran-glycidylmethacrylate (Dex-GMA)/poly(ethylene glycol) (PEG) microspheres were designed and synthesized by polymerization of Dex-GMA emulsified in an aqueous PEG solution. Dex-GMA was prepared by substituting the hydroxyl groups in Dex by GMA. The drug loading and in vitro drug release was evaluated by routine procedure and the biological activity of BMP-loaded microspheres was studied by experimental cytology methods. Recombinant human bone morphogenetic protein-2 (rhBMP-2) were entrapped in dextran-derived microspheres quantitatively and with full preservation of their biological activity. In vitro release kinetics indicated that dextran-derived microspheres could retain rhBMP-2 in a variable manner depending on the preparation and degradation of the microspheres. The release profiles of rhBMP-2 from microspheres as a function of time showed that rhBMP-2 releasing kinetics in vitro fitted to first-order and Higuchi equations. The release profile in vitro was in accord with two phases kinetics law and more than 60% drug were released during 20 days. Cytology studies showed rhBMP-2 microspheres have good biological effects on cultured periodontal ligament cells, and could achieve a longer action time than concentration of rhBMP-2 solution. These properties make those microspheres interesting osteo-conductive BMP carriers, allowing to decrease the amount of implanted factor required for tissue regeneration.

Alkaline Phosphatase↗
PubMed2006

Radiosterilisation of indomethacin PLGA/PEG-derivative microspheres: protective effects of low temperature during gamma-irradiation.

Currently, gamma-irradiation seems to be a good method for sterilising drug delivery systems made from biodegradable polymers. The gamma-irradiation of microspheres can cause several physicochemical changes in the polymeric matrix. These modifications are affected by the temperature, irradiation dose and nature of the encapsulated drug and additives. This study has aimed to evaluate the influence of temperature during the sterilisation process by gamma irradiation in indomethacin PLGA microspheres including a PEG-derivative. Microspheres were prepared by the solvent evaporation method from o/w emulsion and were then exposed to gamma-irradiation. A dose of 25 kGy was used to ensure effective sterilisation. Some microspheres were sterilised with dry ice protection that guaranteed a low temperature during the process whilst others were sterilised without such dry ice protection. The effects of gamma-irradiation on the characteristics of non-loaded PLGA/PEG-derivative and indomethacin loaded PLGA/PEG-derivative microspheres with and without protection were studied. Non-protected microspheres showed changes in their morphological surface, polymer glass transition temperature, molecular weight and release rate of indomethacin after sterilisation. However, microspheres sterilised with protection did not show significant differences after gamma-irradiation exposure. The sterilisation method was satisfactory when the indomethacin loaded microspheres including a PEG-derivative were exposed to gamma-irradiation at low temperature.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Induction of systemic and mucosal immune responses by intranasal administration of alginate microspheres encapsulated with tetanus toxoid and CpG-ODN.

In the induction of systemic and mucosal immunity, particulate antigens are more effective than soluble antigens; possibly because they are more efficiently endocytosed by mucosal-associated lymphoid tissue (MALT) M cells. In this study, we determined the systemic and mucosal immune responses in rabbits following intranasal immunization with encapsulated tetanus toxoid (TT) and CpG-ODN in alginate microspheres. The microspheres were less than 4 microm in diameter. Encapsulation efficiency of TT and CpG-ODN was determined as 47.7+/-6.6 and 34.2+/-7.4, respectively. Release of TT and CpG-ODN in a simulated model with nasal cavity was 14.2+/-3.06 and 36.7+/-2.4% after 4 h. Encapsulated TT preserved its intact structure, but its immunoreactivity was decreased to about 91+/-5%. The highest serum IgG and antitoxin, and nasal lavage IgA titers were observed in groups immunized with microsphere formulations. CpG-ODN as an adjuvant could increase the serum IgG and antitoxin titers when co-administered with TT solution, but its co-encapsulation with TT in alginate microspheres failed to potentiate the systemic immune response while induced high IgA titers in nasal lavages. No hemolysis was occurred on incubation of alginate microspheres and human RBCs. Also after nasal administration of plain microspheres to human volunteers, no local irritation was observed. Intranasal administration of microspheres encapsulated with vaccines showed to be an effective way for inducing a variety of immune responses and that a strong systemic IgG and mucosal IgA responses can be induced in rabbits with intranasal administration of alginate microspheres encapsulated with TT.

Adjuvants, Immunologic↗
PubMed2006

Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine.

This paper describes the synthesis of capecitabine-loaded semi-interpenetrating network hydrogel microspheres of chitosan-poly(ethylene oxide-g-acrylamide) by emulsion crosslinking using glutaraldehyde. Poly(ethylene oxide) was grafted with polyacrylamide by free radical polymerization using ceric ammonium nitrate as a redox initiator. Capecitabine, an anticancer drug, was successfully loaded into microspheres by changing experimental variables such as grafting ratio of the graft copolymer, ratio of the graft copolymer to chitosan, amount of crosslinking agent and percentage of drug loading in order to optimize process variables on drug encapsulation efficiency, release rates, size and morphology of the microspheres. A 2(4) full factorial design was employed to evaluate the combined effect of selected independent variables on percentage of drug release at 5h (response). Regression models were used for the response and data were compared statistically using the analysis of variance (ANOVA). Grafting, interpenetrating network formation and chemical stability of the capecitabine after encapsulation into microspheres was confirmed by Fourier infrared spectra (FTIR). Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) studies were made on drug-loaded microspheres to investigate the crystalline nature of drug after encapsulation. Results indicated amorphous dispersion of capecitabine in the polymer matrix. Scanning electron microscope (SEM) confirmed spherical shapes and smooth surface morphology of the microspheres. Mean particle size of the microspheres as measured by the laser light scattering technique ranged between 82 and 168microm. Capecitabine was successfully encapsulated into semi-IPN microspheres and percentage of encapsulation efficiency varied from 79 to 87. In vitro release studies were performed in simulated gastric fluid (pH 1.2) for the initial 2h, followed by simulated intestinal fluid (pH 7.4) until complete dissolution. The release of capecitabine was continued up to 10h. Release data were fitted to an empirical relationship to estimate the transport parameters. Dynamic swelling studies were performed in the simulated intestinal fluid and diffusion coefficients were calculated by considering the spherical geometry of the matrices.

Acrylic Resins↗
PubMed2006

Development of 5-fluorouracil loaded poly(acrylamide-co-methylmethacrylate) novel core-shell microspheres: in vitro release studies.

Novel poly(acrylamide-methylmethacrylate) copolymeric core-shell microspheres crosslinked with N,N'-methylene bisacrylamide have been prepared by free radical emulsion polymerization using varying amounts of acrylamide (AAm), methylmethacrylate (MMA) and N,N'-methylene bisacrylamide (NNMBA). 5-Fluorouracil was loaded into these microspheres during in situ polymerization (method-I) as well as by the absorption and adsorption technique (method-II). The core-shell microspheres have been characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (X-RD) to understand about the drug dispersion in microspheres. Scanning electron microscopy (SEM) was used to assess the surface morphology of particles prepared. In vitro release of 5-fluorouracil has been studied in terms of core-shell composition, amount of crosslinking agent and amount of 5-fluorouracil in the microspheres. Core-shell microspheres with different copolymer compositions have been prepared in yields ranging 80-85%. DSC and X-RD techniques indicated a uniform distribution of 5-fluorouracil particles in core-shell microspheres, whereas SEM suggested the formation of well-defined core-shell structures. The in vitro drug release indicated that particle size and release kinetics depend upon copolymer composition, amount of crosslinking agent used and amount of 5-fluorouracil present in the microspheres. Prolonged and controlled release of 5-fluorouracil was achieved when drug was loaded by method-I instead of method-II.

Absorption↗
PubMed2004

Localization of bovine serum albumin in double-walled microspheres.

Phase separation of binary blends of various combinations of poly (L-lactide) (PLA), and poly (D,L-lactide-co-glycolide) (PLGA), was investigated using differential scanning calorimetry (DSC). Based on this phase separation phenomenon, double-walled microspheres were fabricated. A model agent, bovine serum albumin (BSA) labeled with fluorescein isothiocyanate (FITC-BSA) was localized in each layer. Scanning electron microscopy (SEM) and fluorescence microscopy (FM) were used to assess the formation of double-walled microspheres and the localization of the drug, respectively. When a 1:1 polymer ratio was used, the FITC-BSA was localized in the outer layer. When the relative ratio of PLGA to PLA was increased to 3:1 using the same overall polymer concentration, the FITC-BSA was localized in the inner core. Release studies were carried out to evaluate the advantage of double-walled microspheres compared to single walled microspheres. Microspheres made with FITC-BSA localized in the inner core exhibited a significantly lower initial release rate compared to microspheres where the drug was located in the outer layer, or compared to microspheres made from PLA only. Hence microspheres with a double-walled morphology have the potential for therapeutic use where a high burst might be detrimental.

Animals↗
PubMed2005

Mapping neutral microclimate pH in PLGA microspheres.

A quantitative ratiometric method based on laser scanning confocal microscopic imaging was developed to create a pixel-by-pixel neutral microclimate pH (5.8-8.0) map inside poly(lactic-co-glycolic acid) (PLGA) microspheres. The method was accurate to within +/-0.2 pH units. PLGA microspheres with encapsulated bovine serum albumin and the pH-sensitive dye, SNARF-1(R) dextran (MW=10 kDa), were prepared by a water-in-oil-in-water solvent evaporation method. The imaging method was used to monitor the pH changes in PLGA microspheres with or without co-encapsulation of acid-neutralizing MgCO3, and for three different microsphere sizes (2.0+/-0.3, 40+/-10 and 137+/-32 microm) during incubation under physiological conditions. The pH of microspheres was significantly higher with co-encapsulated base compared to base-free microspheres, whose microclimate pH was predominantly below the dye detection limit of pH=5.8. The small microspheres displayed a more neutral pH during incubation probably due to their much shorter diffusion path for polymer-dissolved acids compared with medium- and large-size microspheres. The pH mapping technique discussed here may be useful in routine formulation development and for elucidation of mechanisms of microclimate pH development and polymer erosion.

Drug Delivery Systems↗
PubMed2005

Gentamicin-loaded discs and microspheres and their modifications: characterization and in vitro release.

Osteomyelitis is an infection of the bone, and successful treatment involves local administration for about 6 weeks. Gentamicin is a very hydrophilic drug and tends to come out into the water phase when microspheres are fabricated using solvent evaporation method. Hence, spray drying is an option, and it was observed that the release rate tends to be fast when the particle size is small and large particles cannot be prepared by spray drying. In an effort to get better encapsulation efficiency and release rate, we have worked on the possibility of compressing the microspheres into discs and modifying the porosity of the discs by using biocompatible materials like polyethylene glycol (PEG) and calcium phosphates and also on the fabrication of double-walled and composite microspheres. In the case of microspheres, two methods of fabrication both based on solvent evaporation method were employed. The two polymers used are poly-L-lactide (PLLA) and copolymers of poly-DL-lactic-co-glycolic acid (PLGA). One method is based on the spreading coefficient theory for the formation of double-walled microspheres by using single solvent, while the other is based on the property of PLLA not being soluble in ethyl acetate (EA). Characterization to check if the microspheres formed are double-walled was performed. The fabrication method where two solvents, dichloromethane (DCM) and ethyl acetate, were used gave double-walled microspheres, while the other where only dichloromethane was used gave composites. The double-walled microspheres were smaller in size compared to the composites, which were in the range of 100-600 microm. This can be attributed to the difference in the fabrication procedure. We were able to achieve better encapsulation efficiencies of more than 50% and slower release rates, which lasted for about 15 days. It was observed that size played a major role in the encapsulation efficiency and release rates. The possibility of achieving better results by studying the effect of concentration of polymer in solvent and the effect of using different polymers was investigated.

Anti-Bacterial Agents↗
PubMed2005

Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats.

The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L-PLA, D,L-PLA and PLAGA) concentrations were 10% (w/w) in the organic phase; the emulsifiers [sodium carboxymethylcellulose (NaCMC):sodium oleate (SO) and Polyvinyl alcohol (PVA):SO mixture (4:1 w/v)] concentrations were 0.75% in the aqueous phase. Microspheres were analyzed for morphological characteristics, size distribution, drug loading and in vitro release. The release profile of CD/LD from microspheres was characterized in the range of 12-35% within the first hour of the in vitro release experiment. The efficiency of CD- and LD-encapsulated microspheres to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model were also tested. 6-OHDA/CD-LD-loaded microsphere groups exhibited lower rotation scores than 6-OHDA/Blank microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks (p<0.05). CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation.

Animals↗
PubMed2005

The effect of gamma-irradiation on PLGA/PEG microspheres containing ovalbumin.

Poly(ethylene glycol) (PEG) and sodium chloride (NaCl) are excipients used in PLGA microsphere preparation to stabilize proteins and reduce their burst release. No information is till now available in the literature on the effect due to the use of such excipients on the biopharmaceutical performance of gamma-irradiated microparticulate systems. On this purpose, different batches of microspheres containing ovalbumin (OVA) were prepared by using a PLGA 50:50 (average Mr: 13000), different amounts of PEG (Mr: 400 or 4000) and/or sodium chloride. The non-irradiated and irradiated microspheres were characterized in terms of morphology (SEM, particle size distribution), OVA and PEG content and in vitro OVA release. Radiolysis mechanisms of OVA and OVA loaded microspheres were investigated by EPR analysis. Gamma irradiation affects either microsphere morphology or the release of OVA as a function of the amount of PEG, and the use of NaCl. Irradiation significantly reduces release rate of protein from the microspheres containing 15% and 30% of PEG and from controls (microspheres without additives), while no significative effect on protein release rate is highlighted on microspheres containing lower amounts of PEG. EPR investigation shows that increasing amounts of PEG up to 30% have a perturbation effect on OVA radiolysis path.

Excipients↗
PubMed2005

Preparation, characterization and nasal delivery of alpha-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres.

In this study, alpha-cobrotoxin was incorporated into the microspheres composed of poly(lactide-co-glycolide) (PLGA) and poly[1,3-bis(p-carboxy-phenoxy) propane-co-p-(carboxyethylformamido) benzoic anhydride] (P(CPP:CEFB)) and intranasally delivered to model rats in order to improve its analgesic activity. The microspheres with high entrapment efficiency (>80%) and average diameter of about 25 microm could be prepared by a modified water-in-oil-in-oil (w/o/o) emulsion solvent evaporation method. Scanning electron micrograph (SEM) study indicated that P(CPP:CEFB) content played a considerable role on the morphology and degradation of the microspheres. The presence of P(CPP:CEFB) in the microspheres increased their residence time at the surface of the nasal rat mucosa. The toxicity of the composite microspheres to nasal mucosa was proved to be mild and reversible. A tail flick assay was used to evaluate the antinociceptive activity of the microspheres after nasal administration. Compared with the free alpha-cobrotoxin and PLGA microspheres, PLGA/P(CPP:CEFB) microspheres showed an apparent increase in the strength and duration of the antinociceptive effect at the same dose of alpha-cobrotoxin (80 microg/kg body weight).

Administration, Intranasal↗
PubMed2005

Incorporation of protein-eluting microspheres into biodegradable nerve guidance channels for controlled release.

Nerve guidance channels (NGCs) promote axonal regeneration after transection injury of the peripheral nerve or spinal cord, yet this regeneration is limited. To enhance regeneration further, we hypothesize that localized delivery of therapeutic molecules combined with the NGC is required. In an attempt to achieve such an NGC, we designed and synthesized a novel NGC in which protein-encapsulated microspheres were stably incorporated into the tube wall. Specifically, poly(lactide-co-glycolide) (PLGA 50/50) microspheres were physically entrapped in the annulus between two concentric tubes, consisting of a chitosan inner tube and a chitin outer tube. Taking advantage of the extensive shrinking that the outer chitin tube undergoes with drying, >15 mg of microspheres were loaded within the tube walls. Using BSA-encapsulated microspheres as the model drug delivery system, BSA was released from microsphere loaded tubes (MLTs) for 84 days, and from freely suspended PLGA microspheres for 70 days. An initial burst release was observed for both MLTs and free microspheres, followed by a degradation-controlled release profile that resulted in a higher release rate from MLTs initially, which was then attenuated likely due to the buffering effect of chitin and chitosan tubes. Epidermal growth factor (EGF), co-encapsulated with BSA in PLGA 50/50 microspheres in MLTs, was released for 56 days with a similar profile to that of BSA. Released EGF was found to be bioactive for at least 14 days as assessed by a neurosphere forming bioassay.

Algorithms↗
PubMed2001

Biodegradable microspheres of novel segmented poly(ether-ester-amide)s based on poly(epsilon-caprolactone) for the delivery of bioactive compounds.

A novel class of multiblock poly(epsilon-caprolactone)-based polymers containing hydrophilic trioxyethylene segments and potentially relevant to the delivery of drugs is described in this work. L-phenylalanine residues may also be inserted into the hydrophilic blocks to generate peptide bonds susceptible to enzymatic attack. The investigated polymers were poly(ether-ester-amide)s (PEEAs) obtained by a two-step polymerization procedure from OH-end capped low molecular weight poly(epsilon-caprolactone), sebacoyl chloride and either 4,7,10-trioxa-1,13-tridecanediamine (PEEA1) or 1,13-di(L-phenylalaninamido)-4,7,10-trioxatridecane (PEEA2). PEEAs were characterized by 1H-NMR spectroscopy, differential scanning calorimetry, gel permeation chromatography and were tested for their suitability in producing microspheres. Particles obtained by the single emulsion-solvent evaporation technique were regular and smooth (SEM analysis) showing a monomodal distribution of dimensions. To assess the potentiality of PEEAs in the oral delivery of drugs, three model compounds with different pKa and solubilities--diclofenac, nicardipine and dicumarol--were encapsulated within PEEA microspheres. For the sake of comparison, microspheres prepared from poly(epsilon-caprolactone) (PCL) with a molecular weight similar to PEEAs were also prepared and tested. The release of diclofenac from all the microspheres was very rapid (100% released within 2 h) whereas nicardipine release was slower and biphasic. The initial phase approximated a near zero-order release, being the fraction of nicardipine released after 8 h from PEEA microspheres higher with respect to PCL particles (about 70 vs. 30%). This result was ascribed to the lower crystallinity of PEEAs with respect to PCL which results in a facilitated access of water molecules through the polymer matrix. The lipophilic-unionizable dicumarol was released from PEEA microspheres at a very slow rate. Therefore, dicumarol-loaded PEEA2 microspheres allowed the study of the influence on the release rate of the insertion into the polymer chain of enzymatically degradable bonds. PEEA2 microspheres released dicumarol at the same rate in a medium with or without the proteolitic enzyme alpha-chymotrypsin. Although the insertion of an isolated amino acid was not sufficient to confer enzyme susceptibility to the polymer, the distinctive properties of PEEAs make their use very attractive in the field of controlled release.

Amides↗