Microsphere Preparations Research Articles

Comparison of Absorbents and Drugs for Internal Decorporation of Radiocesium: Advances of Polyvinyl Alcohol Hydrogel Microsphere Preparations Containing Magnetite and Prussian Blue

Radiocesium nuclides, used as a gamma ray source in various types of industrial equipments and found in nuclear waste, are strictly controlled to avoid their leakage into the environment. When large amounts of radiocesium are accidentally incorporated into the human body, decorporation therapy should be considered. Although standard decorporation methods have been studied since the 1960s and were established in the 1970s with the drug Radiogardase(®) (a Prussian blue preparation), application of recent advances in pharmacokinetics and ethical standards could improve these methods. Here we designed a modern dosage form of hydrogel containing cesium-absorbents to alleviate intestinal mucosa irritation due to the cesium-binding capacity of the absorbents. The effectiveness of the dosage form on fecal excretion was confirmed by quantitative mouse experiments. The total cesium excretion rate of the crystal form (1.37±0.09) was improved by the hydrogel form (1.52±0.10) at the same dose of Prussian blue, with a longer gastrointestinal tract transit time. Using a mouse model, we compared the effects of several drugs on fecal and urinary excretion of internal cesium, without the use of absorbents. Only phenylephrine hydrochloride significantly enhanced cesium excretion (excretion rate of 1.17±0.08) via the urinary pathway, whereas none of the diuretic drugs tested had this effect. These findings indicate that modifying the dosage form of cesium absorbents is important for the decorporation of internal radiocesium contamination.

Occupational radiation exposure of medical staff performing ⁹⁰Y-loaded microsphere radioembolization.

Radioembolization of liver cancer with (90)Y-loaded microspheres is increasingly used but data regarding hospital staff exposure are scarce. We evaluated the radiation exposure of medical staff while preparing and injecting (90)Y-loaded glass and resin microspheres especially in view of the increasing use of these products. Exposure of the chest and finger of the radiopharmacist, nuclear medicine physician and interventional radiologist during preparation and injection of 78 glass microsphere preparations and 16 resin microsphere preparations was monitored. Electronic dosimeters were used to measure chest exposure and ring dosimeters were used to measure finger exposure. Chest exposure was very low for both products used (<10 μSv from preparation and injection). In our experience, finger exposure was significantly lower than the annual limit of 500 mSv for both products. With glass microspheres, the mean finger exposure was 13.7 ± 5.2 μSv/GBq for the radiopharmacist, and initially 17.9 ± 5.4 μSv/GBq for the nuclear medicine physician reducing to 13.97 ± 7.9 μSv/GBq with increasing experience. With resin microspheres, finger exposure was more significant: mean finger exposure for the radiopharmacist was 295.1 ± 271.9 μSv/GBq but with a reduction with increasing experience to 97.5 ± 35.2 μSv/GBq for the six most recent dose preparations. For administration of resin microspheres, the greatest mean finger exposure for the nuclear medicine physician (the most exposed operator) was 235.5 ± 156 μSv/GBq. Medical staff performing (90)Y-loaded microsphere radioembolization procedures are exposed to safe levels of radiation. Exposure is lower than that from treatments using (131)I-lipiodol. The lowest finger exposure is from glass microspheres. With resin microspheres finger exposure is acceptable but could be optimized in accordance with the ALARA principle, and especially in view of the increasing use of radioembolization.

Formulation and Optimisation of Sustained Release Spray-Dried Microspheres of Glipizide Using Natural Polysaccharide

The objective of this study was to investigate the combined influence of three independent variables in the preparation of glipizide microspheres by the spray-drying method. A three factor, three level Box-Behnken design was used to derive polynomial equations and construct response surface plots to predict responses. The independent variables selected were concentration of polymer (xyloglucan) (X1), amount of crosslinking agent (X2), and feed rate (X3). Fifteen batches were prepared and evaluated for percentage drug entrapment and time for 80% drug release (t80). Response surface plots were constructed to demonstrate the combined effects of factors X1, X2, and X3 on response percent entrapment. The optimal microsphere preparations displayed a percent entrapment between 96.96 and 98.11 and a t80 between 420 and 439 min. The microspheres had particle size between 3 and 6 microns, and differential scanning chromatography thermograms showed the presence of glipizide in amorphous form in microspheres. Multiparticulate dosage forms are pharmaceutical formulations in which the active substance is present as number of small independent subunits. The microspheres as drug delivery systems are especially suitable for providing oral controlled release formulations with low risk of dose dumping, Microspheres can be blended suitably to attain different release patterns. Glipizide is recommended orally for treatment of type II diabetes and is administered in 2 or 3 doses of 2.5 to 10 mg per day. The development of controlled-release dosage form would offer effective control by releasing drug over period of time. The present work describes formulation of microspheres containing glipizide using the tamarind seed polysaccharide or xyloglucan as carrier. The spray-drying method was used to formulate the microspheres and variables (concentration of xyloglucan, amount of crosslinking agent, and feed rate) affecting performance parameters such as time for 80% drug release and percent drug entrapment were optimized using a statistical design (Box Behnken design). The microspheres had particle size between 3 and 6 microns, had entrapment between 97 and 99%, and sustained the drug release beyond 7 hours.

Novel approach for preparing nontoxic stealth microspheres for drug delivery

Normal.dotm 0 0 1 124 709 Uni 5 1 870 12.0 0 false 18 pt 18 pt 0 0 false false false Polyethylene glycol 2000 (PEG) entrapped, bovine serum albumin (BSA) microspheres were prepared and optimized. These microspheres were then analyzed to understand the stealth effect to the microspheres imparted by incorporated polyethylene glycol (PEG). Microsphere preparations (formulations) were studied for particle size, zeta potential, free BSA content, and in-vitro uptake by human micro-vascular endothelial cells (HMECs). The results demonstrate, a formulation containing 37.5 % PEG (w/w) exhibits an acceptable particle size of &lt;5 µm, good suspendibility with zeta potential of -35 mV, and confers some degree of stealth property to the microspheres. These non-toxic, biodegradable and long circulating microspheres have the potential to be used for extended intravenous (IV) drug delivery. Statistical analysis done by ANOVA and results with p&lt;0.05 were considered significant.

Preparation and evaluation of a novel gastric mucoadhesive sustained-release acyclovir microsphere

Objective: The objective of this study was to prepare a novel gastric mucoadhesive sustained-release acyclovir (AV)-resinate microsphere. Methods: First, AV absorption ratio was quantified in a rat gastrointestinal (GI) tract model. AV-resinate was prepared by bath method and used as cores to prepare microspheres by an emulsion solvent diffusion technique with carbopol 934 as coating material. GI transit test of the prepared microspheres was carried out in rats and beagle dogs, followed by the in vivo bioavailability evaluation of the microspheres in beagle dogs. Results: The AV absorption ratio in different segments of rat's GI track for 3 hours was as following: stomach 9.46 ± 0.62%, duodenum 20.22 ± 1.50%, jejunum 15.7 ± 1.33%, ileum 9.15 ± 1.01%, and colon 4.59 ± 0.48%. These results showed that AV was mainly absorbed in the stomach and upper intestine. The average diameter of the microspheres was 115.3 μm. The microspheres had a drug content of 33.3 ± 0.7% (w/w) and a sustained-release profile for 12 hours in vitro. The mucoadhesive test in rats and beagle dogs showed that most of the microspheres were retained in the stomach 6 hours after oral administration. The in vivo pharmacokinetics test revealed that the microsphere and reference (AV tablets) preparations have no significant difference for Cmax. The tmax has increased from 2.33 hours (reference) to 5 hours (test). Meanwhile, the relative bioavailability of AV microspheres was 145%. Conclusion: A novel AV-resinate microsphere was prepared. The microspheres were proved to be gastric mucoadhesive and sustained-release with higher bioavailability.

Pharmacokinetic and biodistribution studies of Amphotericin B microspheres

The pharmacokinetics of Amphotericin B (AmB) from polyethylene glycol 2000 (PEG 2000) entrapped cross-linked bovine serum albumin (BSA) microsphere formulations were investigated and compared with solution formulation. The microsphere preparations were characterized for particle size using electron microscopy, zeta potential and encapsulation efficiency. The microsphere formulations demonstrated a sustained release of AmB for a longer period of time, with no rise in plasma creatinine and potassium levels. The enhanced AmB accumulation in lungs was observed which could be of importance since lungs are the primary target in most fungal infections. The stealth property of submicron cross-linked BSA microspheres in formulations containing PEG 2000 (formulation F-2N) and without PEG 2000 (formulation F-1N) was also evaluated. There was no evidence that microspheres embedded with PEG remained longer in circulation; however, it was noticed that the internalization of formulation F-2N microspheres was delayed when compared with microspheres from formulation F-1N.

Liposomes act as stronger sub-unit vaccine adjuvants when compared to microspheres

The ability of liposomes and microspheres to enhance the efficacy of a sub-unit antigen was investigated. Microspheres were optimised by testing a range of surfactants employed in the external aqueous phase of a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation process for the preparation of microspheres—composed of poly(d,l-lactide-co-glycolide) and the immunological adjuvant dimethyl dioctadecyl ammonium bromide (DDA)—and then investigated with regard to the physico-chemical and immunological characteristics of the particles produced. The results demonstrate that this parameter can affect the physico-chemical characteristics of these systems and subsequently, has a substantial bearing on the level of immune response achieved, both humoural and cell mediated, when employed for the delivery of the sub-unit tuberculosis vaccine antigen Ag85B-ESAT-6. Moreover, the microsphere preparations investigated failed to initiate immune responses at the levels achieved with an adjuvant DDA-based liposome formulation (DDA-TDB), further substantiating the superior ability of liposomes as vaccine delivery systems.

Preparation and evaluation of waxes/fat microspheres loaded with lithium carbonate for controlled release

To minimize the unwanted toxic effects of anti maniac drug lithium carbonate by kinetic control of drug release, it was entrapped into gastro resistant, biodegradable, waxes and fat such as beeswax, cetostearyl alcohol, spermaceti and cetylalcohol microspheres using meltable emulsified dispersion cooling induced solidification technique utilizing a wetting agent. Solid, discrete, reproducible free flowing microspheres were obtained. The yield of the microspheres was up to 90.0%. More than 98.0% of the isolated microspheres were of particle size range 115 to 855 mm. The microspheres had smooth surfaces, with free flowing and good packing properties. Scanning electron microscope confirmed their spherical structures within a size range of 339-355 mm. The drug loaded in waxes and fat microspheres was stable and compatible, as confirmed by DSC and FTIR studies. The release of drug was controlled for more than 8 hours. Intestinal drug release from waxes/ fat microspheres was studied and compared with the releases behavior of commercially available formulation Intalith CR®-450. The release kinetics followed different transport mechanisms. The drug release performance was greatly affected by the materials used in microsphere preparations, which allows absorption in the intestinal tract.

Preparation and evaluation of Eudragit S 100 microspheres as pH-sensitive release preparations for piroxicam and theophylline using the emulsion-solvent evaporation method

Microencapsulation of the anti-inflammatory drug piroxicam and the anti-asthmatic drug theophylline was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Microspheres of both drugs that are different in the chemical nature and size were successfully encapsulated at a theoretical loading of 25% with the pH sensitive Eudragit S 100 polymer using the emulsion-solvent evaporation method. Solvent composition, stirring rate and the volume of the external phase were adjusted to obtain reproducible, uniform and spherical microspheres. The size distribution of microsphere batches generally ranged from 125–500 µm with geometric means close to 300 µm. Optical light microscopy was used to identify the microsphere shape. Drug loading was determined by completely dissolving the microspheres in an alkaline borate buffer at pH 10. In vitro dissolution studies were carried out on the microspheres at 37°C (±0.5°C) at 100 rpm with USP Dissolution Apparatus II using the procedure for enteric-coated products at two successive different pH media (1.2 and 6.5). Both preparations exhibited an initial rapid release in the acidic medium with theophylline showing a larger increase in the amount released during this stage. The drug release was sustained for both preparations at pH 6.5 with theophylline microspheres, showing more extended release. Drug release rate kinetics followed a Higuchi spherical matrix model for both microsphere preparations.

Efficacy of mitoxantrone-loaded albumin microspheres for intratumoral chemotherapy of breast cancer

Systemic toxicity of intravenously delivered chemotherapy is a limiting factor in the treatment of many cancers. We have shown that intratumoral injection of antineoplastic drugs can provide high localized drug concentrations with greatly reduced systemic toxicity. Using albumin microspheres as a drug carrier, localized and sustained release of chemotherapeutic drugs has been achieved by intratumoral injection, thus increasing the intratumoral dose and antitumor efficacy. Microspheres provide the advantages of localized, prolonged drug release. The efficacy and toxicity of intratumoral free mitoxantrone or mitoxantrone-loaded albumin microspheres were evaluated in a murine breast cancer model. In the same model, a combination of these two therapies was also evaluated. Results indicated that intratumoral mitoxantrone, especially in microsphere preparations, significantly improved survival and decreased systemic toxicity.

Hydrophilic poly( dl-lactide-co-glycolide) microspheres for the delivery of DNA to human-derived macrophages and dendritic cells

Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres have a proven track record for drug delivery and are suggested to be ideal carrier systems to target therapeutics into phagocytic cells such as macrophages (MΦs) and dendritic cells (DCs). Microspheres prepared by spray-drying from different PLGA-type polymers were evaluated regarding their effect on phagocytosis, intracellular degradation and viability of human-derived macrophages MΦs and DCs. Even the microspheres prepared from the most hydrophilic polymer RG502H, were efficiently phagocytosed by primary human MΦs and DCs. Interestingly, uptake of PLGA microspheres by DCs as potent immune modulator cells was almost as efficient as uptake by the highly phagocytic MΦs. Phagocytosed microspheres remained inside the cells until decay with none of the microsphere preparations induced significant apoptosis or necrotic cell death. Acidic pH and the phagosomal environment inside the cells enhanced microsphere decay and release of encapsulated material. Degradation of microspheres consisting of the most hydrophilic PLGA polymer RG502H occurred in a reasonable time frame of less than 2 weeks ensuring the release of encapsulated drug during the life span of the cells. To explore important technical and biological aspects of DNA microencapsulation, we have studied DNA loading and in vitro DNA release of microspheres from different PLGA type polymers. Hydrophobicity and molecular weight of the PLGA polymers had profound influence on both the encapsulation efficiency of DNA and its release kinetics in vitro: the hydrophilic polymers showed higher encapsulation efficiency and faster release of intact DNA compared to the hydrophobic ones. These results suggest that microspheres from the PLGA polymer RG502H have improved characteristics for DNA delivery to human MΦs and DCs.

Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis

Background. Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. Aims. To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. Patients. Patients with pancreatic exocrine insufficiency due to cystic fibrosis. Methods. Patients were assigned to the crossover treatment with Creon ® or Pancrease ® for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. Results and conclusions. Of the 33 60 patients who expressed a preference for one of the two treatments, 30 preferred Creon ® while only 3 patients preferred Pancrease ® (p<0. 001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon ®. The results of this study showed a preference in favour of Creon ® probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease ®.

Biodegradable microspheres containing influenza A vaccine: immune response in mice

A monovalent influenza split vaccine was microencapsulated in poly( d, l-lactic-co-glycolic acid) (PLGA) and ABA triblock copolymers using a W/O/W double emulsion technique. To stabilize the antigen, influenza vaccine was also coencapsulated with liposomes. Antigen release from microspheres was determined in vitro using a hemagglutinin-specific ELISA. PLGA-microspheres with liposomes released immunoreactive hemagglutinin in a pulsatile manner, a preferred feature for the development of a single dose vaccine delivery system. Influenza hemagglutinin specific IgG and neutralizing antibody responses were studied in BALB/c mice following subcutaneous injection of different microsphere preparations. PLGA-microspheres elicited a significantly higher primary IgG response compared to nonencapsulated antigen. ABA-microspheres seemed to be less immunogenic than PLGA-microspheres based on the IgG antibody response, however, similar levels of neutralizing antibodies were observed after eight weeks with both polymers. Entrapment of the antigen in liposomes prior to microencapsulation did not further enhance the immune response. The immunopotentating effect of the antigen-loaded microspheres was prominently enhanced when they were given as suspension in fluid antigen, suggesting that free antigen may serve as priming and microencapsulated antigen as booster dose. Eight weeks after a single subcutaneous immunization with PLGA or ABA-microspheres neutralizing antibodies were as high as those obtained after two subcutaneous administrations of fluid vaccine four weeks apart. Microencapsulated influenza antigen may have potential for a single dose vaccine delivery system with adjuvant properties.

What to Do when a Patient with Exocrine Pancreatic Insufficiency Does Not Respond to Pancreatic Enzyme Substitution

In the majority of patients, pancreatin microsphere preparations containing 25,000–40,000 FIP units of lipase will lead to a clinical improvement and reduction of steatorrhea in patients with exocrine pancreatic insufficiency. In patients failing to respond, the following stepwise procedure is recommended: increasing enzyme dosage; checking the patient’s compliance; reevaluating the diagnosis; and as a last resort to decrease fat intake or adding H₂-blockers or proton pump inhibitors. Although this stepwise procedure is time-consuming, it is necessary to prevent in patients not responding to pancreatic enzyme substitution the development of late complications of exocrine pancreatic insufficiency.

Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease.

Severe pancreatic exocrine insufficiency leading to malabsorption of nutrients is one of the most important late features of chronic pancreatitis. In contrast to other key enzymes, pancreatic synthesis and secretion of lipase is impaired more rapidly, its intraluminal survival is shorter due to its higher susceptibility against acidic and proteolytic denaturation, and its luminal digestive action is hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea is in general more severe and occurs several years before clinical malabsorption of protein or starch. Apart from the detrimental effects of nutrient deficiency, profound alterations of upper gastrointestinal secretory and motor functions may be an additional and hitherto underestimated consequence of increased nutrient delivery to distal intestinal sites. Effective reduction of nutrient malabsorption in pancreatic insufficiency requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. Modern enteric-coated pancreatin microsphere preparations attempt to achieve this by optimizing the size of individual microspheres and chemical properties of the coating. However, lipid digestion cannot be completely normalized in most patients by current standard therapy. In the future, acid and protease stable bacterial and fungal lipases with additional pH optima in the acidic milieu or animal or bioengineered human gastric lipase preparations may offer superior therapeutic alternatives. This review first summarizes current knowledge about secretion and luminal fate of pancreatic enzymes and their effects on nutrient digestion in health and chronic pancreatitis. Second, rationale, current standards, options, and future aspects of enzyme replacement therapy are discussed.

Pancreatic dysfunction and treatment options.

Pancreatic steatorrhea and pancreatic diabetes are the dominant symptoms of patients in the decompensated stage of chronic pancreatitis (CP). In this stage, the nutritional state is greatly disturbed and hypoglycemia and labile infection are involved. Pancreatic enzyme replacement therapy is the principal treatment method for pancreatic steatorrhea. Before initiating this therapy, dietary fat intake must be determined and pancreatic lipase and bicarbonate secretion function must be evaluated. Upper small intestinal pH is regulated by gastric acid secretion, and abnormal gastric emptying changes lipolysis. In addition, precipitation of bile acids in the upper small intestine and ileal brakes due to undigested fats and carbohydrates must be considered. Porcine pancreatin, bacterial lipase, and acid-resistant fungal lipase are used as enzymes for replacement therapy. Conventional, entero-coating, and enteric-coated microsphere preparations of porcine pancreatin are available for treatment and are formulated to protect against gastric acids, to dissolve enzymes at optimum pH, and to be emptied simultaneously with food from the stomach. Gastric acid secretion suppressants, such as H2 blockers or a proton pump inhibitor, can also be used concomitantly with pancreatin preparations. In consideration of both strengths and weaknesses of these preparations, types and dosages of enzyme replacement therapy should be carefully prescribed, and fecal fats should be examined repeatedly by a simple and rapid method during treatment. Attention should also be paid to changes in body weight and nutritional indices (e.g., nutritional parameters, fat-soluble vitamins). The relationship between carbohydrate maldigestion/malabsorption in CP patients and treatment of pancreatic diabetes are topics for future research.

Gastric transit and pharmacodynamics of a two-millimeter enteric-coated pancreatin microsphere preparation in patients with chronic pancreatitis.

It has been suggested that enteric-coated pancreatin microsphere (ECPM) preparations with sphere sizes larger than 1.7 mm pass through the stomach at a slower rate than a meal and therefore may be less efficacious in restoring pancreatic enzyme activity than preparations with smaller sphere sizes. The aim of this study was to investigate the gastric transit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneously measure enzyme activities in eight patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Gastric transit was assessed by double-isotope scintigraphy. A pancake was labeled with 99mTc. A 2-mm ECPM preparation was labeled with 171Er. Intraluminal pancreatic enzyme activities were assessed during a 6-hr period with the cholesteryl-[14C]octanoate breath test (for carboxyl ester lipase activity) and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test (for chymotrypsin activity). The ECPM preparation passed through the stomach more rapidly (median 24 min) than the pancake (median 52 min, P < 0.05). During ECPM therapy, mean cumulative 14CO2 outputs rose significantly from 30% to 70% (P < 0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasma PABA concentrations rose significantly from 46% to 87% (P < 0.05) and were not significantly different from outcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass through the stomach more slowly than a solid meal, but in fact faster. Digestion of ester lipids and proteins showed an improvement to subnormal and normal levels, respectively.

Single shot with tetanus toxoid in biodegradable microspheres protects mice despite acid-induced denaturation of the antigen

Tetanus toxoid encapsulated in microspheres consisting of biodegradable polyesters, prepared by four different manufacturers were evaluated with respect to antigenic load, in vitro release pattern, antigen integrity and immunogenicity. In vitro release studies over periods up to 140 days indicated that only during the first days tetanus toxoid was released. Although some preparations were designed to release their antigen content in a pulsatile manner, this was never observed in vitro. A single immunization with 0.3 Lf tetanus toxoid in microspheres induced substantial humoral responses, in most cases higher than one immunization with plain tetanus toxoid, sometimes higher than one dose of alum-adsorbed toxoid but always lower than booster immunizations. It is shown that the moderate (no booster effect) performance of the microsphere preparations is probably due to acid induced denaturation of the antigen. Despite this drawback, protection level in mice after challenge with 50 LD 50 1 year after one immunization with microspheres was, on average, substantially higher than mice receiving plain tetanus toxoid.

Evaluation of the bioadhesive properties of hyaluronan derivatives: Detachment weight and mucociliary transport rate studies

Hyaluronan of various molecular weights, and microspheres made from several of its esters, were assessed for adhesiveness in vitro by means of detachment weight and mucociliary transport rate. Microspheres made from esters of alginic acid and gellan gum were also evaluated. The results were compared with those obtained from Carbopol 974 which was used as a positive control. Hyaluronan and its autocross-linked esters displayed comparable adhesion to Carbopol in both studies. All microsphere preparations were less adhesive than Carbopol ( p < 0.05, Mann-Whitney U-test) when tested for detachment weight (using mucosal epithelium) and mucociliary transport rate. Adhesion to a mucus gel was similar for most preparations. Hyaluronan has been shown to possess excellent adhesion in vitro. Although formulation of hyaluronan into microspheres tends to reduce its inherent adhesive properties, the microspheres formed displayed significantly decreased mucociliary clearance. The inclusion of drug into such a biodegradable and biocompatible dosage form is an attractive prospect for transmucosal delivery.

Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) microspheres.

Purified Bordetella pertussis antigens, encapsulated in biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) microspheres, were evaluated for their immunogenicity and ability to elicit a protective immune response against B. pertussis respiratory infection. Microencapsulated pertussis toxoid, filamentous hemagglutinin, and pertactin all retained their immunogenicity when administered parenterally. Intranasal immunization with a low dose (1 micrograms) of encapsulated filamentous hemagglutinin, pertussis toxoid, or pertactin elicited strong specific immunoglobulin G and immunoglobulin A antibody responses in respiratory secretions that were greater in magnitude than the responses elicited by the same doses of unencapsulated antigen. Intranasal immunization with as little as 1 micrograms of encapsulated pertussis antigen prior to infection reduced the bacterial recovery by 3 log10 CFU. However, intranasal immunization with the same low doses of unencapsulated antigens did not reduce infection. Intranasal administration of a combination of 1 micrograms of each of the microencapsulated pertussis antigens was more effective in reducing bacterial infection than administration of any single microencapsulated antigen. Intranasal administration of microencapsulated B. pertussis antigens elicits high levels of specific antibody coinciding with protection against infection when these microspheres are administered to the respiratory tract. These data provide evidence of the respiratory adjuvanticity of three different DL-PLC microsphere preparations, each of which contains a unique B. pertussis antigen.