Albumin Microspheres Research Articles

Protein Microspheres with Unique Green and Red Autofluorescence for Noninvasively Tracking and Modeling Their in Vivo Biodegradation.

Bovine serum albumin (BSA) microspheres were prepared through a facile and low-cost route including a high-speed dispersion of BSA in cross-linking solution followed by spray drying. Interestingly the as-prepared BSA microspheres possess unique blue-green, green, green-yellow, and red fluorescence when excited by specific wavelengths of laser or LED light. The studies of UV-visible reflectance spectra and fluorescence emission spectra indicated that four classes of fluorescent compounds are presumably formed during the fabrication processes. The formation and the potential contributors for the unique green and red autofluorescence were also discussed and proposed though the exact structures of the fluorophores formed remain elusive due to the complexity of the protein system. The effect of spray-drying conditions on the morphology of spray-dried samples was investigated and optimized. FTIR was further employed to characterize the formation of the functional groups in the as-prepared autofluorescent microspheres. Good in vitro and in vivo biocompatibility was demonstrated by the cytotoxicity test on the A549 cancer cells and tissue histological analysis, respectively. The autofluorescent BSA microspheres themselves were then applied as a novel tracer for convenient tracking/modeling of the biodegradation of autofluorescent BSA microspheres injected into mouse model based on noninvasive, time-dependent fluorescence images of the mice, in which experimental data are in good agreement with the proposed mathematical model. All these studies indicate that the as-developed protein microspheres exhibiting good biocompatibility, biodegradability, and unique autofluorescence, can significantly broaden biomedical applications of fluorescent protein particles.

High azithromycin concentration in lungs by way of bovine serum albumin microspheres as targeted drug delivery: lung targeting efficiency in albino mice.

BackgroundFollowing administration, the antibiotic travels freely through the body and also accumulates in other parts apart from the infection site. High dosage and repeated ingestion of antibiotics in the treatment of pneumonia leads to undesirable effects and inappropriate disposition of the drug. By way of targeted lung delivery, this study was intended to eliminate inappropriate azithromycin disposition and to achieve higher azithromycin concentration to treat deeper airway infections.MethodsThe Azithromycin Albumin Microspheres (AAM) was prepared by emulsion polymerization technique. The optimized AAM was subjected to in vitro release study, release kinetics, XRD and stability studies. Further, in vivo pharmacokinetics and tissue distribution of azithromycin released from AAM and azithromycin solution in albino mice was investigated to prove suitability of moving forward the next steps in the clinic.ResultsThe mean particle size of the optimized AAM was 10.02 μm, an optimal size to get deposited in the lungs by mechanical entrapment. The maximum encapsulation efficiency of 82.3 % was observed in this study. The release kinetic was significant and best fitted for Korsmeyer-Peppas model (R2 = 0.9962, n = 0.41). The XRD and stability study showed favorable results. Azithromycin concentration in mice lungs (40.62 μg g−1, 30 min) of AAM was appreciably higher than other tissues and plasma. In comparison with control, azithromycin concentration in lungs was 30.15 μg g−1 after 30 min. The azithromycin AUC (929.94 μg h mL−1) and intake rate (re) (8.88) for lung were higher and statistically significant in AAM group. Compared with spleen and liver, the targeting efficacy (te) in mice lung increased by a factor of 40.15 and ~14.10 respectively. Subsequently by a factor of 8.94, the ratio of peak concentration (Ce) in lung was higher in AAM treated mice. The AAM lung tissue histopathology did not show any degenerative changes.ConclusionsHigh azithromycin concentration in albino mice lung was adequately achieved by targeted drug delivery.

Abstract 4411: Oral drug formulations containing microspheres

Abstract Oral anticancer drug formulations are considerably favorable not only for patient adherence, but also for ease of administration. The main objective of the present research was to develop extended-release capsule formulations containing doxorubicin hydrochloride-encapsulated albumin microspheres. Albumin-based polymeric microspheres were evaluated as a potential platform technology for providing extended-release of oral dosage formulations. Bovine serum albumin microspheres were prepared by spray drying and characterized for their physicochemical properties. Scanning electron microscopy (SEM) was used to analyze the size, surface morphology, and size distribution of the drug-loaded microspheres. Zeta potential measurements were carried out to assess the surface properties and stability of the microsphere formulations. Dissolution studies were conducted to analyze the release profiles of the microspheres and capsule-containing microsphere drug formulations. SEM analysis indicated that microspheres were less than 2-μm in size, which is considered to be optimal for uptake by the enterocytes. The average Zeta potential measurements were approximately -30 mV. Additionally, the data showed that microspheres, which contained 1% BSA and 0.1% glutaraldehyde, provided a drug release profile that is desirable for cancer therapy. Both microsphere and capsule-encapsulating microsphere formulations were shown to provide extended-release of the drug over 36 hours. Thus, capsules containing biodegradable microspheres show potential for effective delivery of oral drug formulations. Citation Format: Duc P. Do, Alexander Kar. Oral drug formulations containing microspheres. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4411. doi:10.1158/1538-7445.AM2015-4411

Formulation and characterization of gentamicin-loaded albumin microspheres as a potential drug carrier for the treatment of E. coli K88 infections

The aim of this study was to formulate and characterize gentamicin-loaded albumin microspheres for their potential therapeutic use in E. coli K88 infections. Based on in vitro assays, it is proposed that microspheres may serve as a carrier of gentamicin and may provide localized antibacterial activity in the treatment of porcine colibacillosis. Gentamicin-albumin microspheres (GAM) were obtained using a water/oil (W/O) emulsion followed by cross-linking with different concentrations of glutaraldehyde. Electron microscopy showed spherical particles with indentations. The average size of the GAM was 10.5-12.3 µm. At pH 7.2, the release kinetics of gentamicin from the GAM was successfully described as an initial burst defined by a first order equation. Gentamicin release was unaffected by the glutaraldehyde concentrations used but was affected by acidic conditions. The behavior of gentamicin release from the GAM was not altered by digestion with trypsin and chymotrypsin at pH 7.2. Additionally, the concentration of gentamicin released from GAM to reach antibacterial activity was similar to that of free gentamicin against E. coli K88. This work shows the potential use of GAM as therapeutic vehicles of gentamicin to counteract intestinal infections in pigs

New Perspectives in Reducing Amyloid Aggregation and Toxicity

AbstractOne of the fundamental biochemical characteristics of Alzheimer′s Disease (AD) is the intercellular accumulation of amyloid beta (Aβ) peptide plaques in the brain. Although there is not yet a cure for AD, major efforts have been made to identify antiamyloidogenic agents and therapeutic strategies to treat this disease and related conditions. Our group focuses on inhibiting the aggregation and toxicity of Aβ using two distinct approaches. The first involves covalently attaching the sequence‐derived core amyloidogenic amino acid fragment KLVFF to the surfaces of serum albumin microspheres. These particles bind soluble Aβ with high affinity, inhibit its aggregation, reduce its toxicity, and decrease the inflammation induced by its aggregates. Microsphere‐bound Aβ stimulates microglia and is phagocytosed via a different mechanism from that used for Aβ removal, so enabling its clearance even by defective cells. Our second approach utilizes self‐assembled cyclic D,L‐α‐peptides as conformational mimics of the amyloid fibril architecture that inhibit the aggregation and cytotoxicity of Aβ. Here, we review these strategies and their mechanisms of action.

Preparation and imaging of rhenium-188 labeled human serum albumin microsphere in orthotopic hepatoma rats

ObjectiveThe present study relates to a method for preparing 188Re-labeled human serum albumin microspheres (HSAM) by 188Re(I)-tricarbonyl ion(188Re(OH2)3(CO)3)+). This radioactive particle can be subjected to radioembolization for liver tumor. MethodsThe particle sizes and conformations of HSA microspheres were analyzed by Particle sizes-Malvern mastersizer and Scanning Electron Microscope (SEM). For preparing 188Re(I)-tricarbonyl ion, the 188ReO4- was eluted from a 188W/188Re generator with saline. The radio labeling efficiency was analyzed with high-performance liquid chromatography (HPLC). Amino borane-reduced 188ReO4-was interacted with carbon oxide to form (188Re(OH2)3(CO)3]+). For preparing 188Re-HSA microspheres, the 188Re(I)-tricarbonyl ion was added into a vial with HSA microspheres. The in vitro stability was investigated. The rat was injected with 188Re-HSA microspheres via hepatic artery route. Nano-SPECT/CT Imaging was acquired after injection of 188Re-HSA microspheres. ResultsThe shape of HSA microsphere was rough surfaced sphere or oval-shaped. The particle size was distributed between 20 and 35μm. In the RP-HPLC-UV chromatography, the yield of 188Re(I)-tricarbonyl ion was 75–80%. The labeling efficiency of 188Re-HSA microspheres in this method was more than 85%. After incubation, the 188Re(I)-tricarbonyl ion labeled HSA microspheres were found to be stable in vitro in normal saline and rat plasma. The result of Nano-SPECT/CT Imaging quantification analysis indicated that the percentage of injection dose %ID was maintained at 95% ID-88% ID from 2 to 72h after injection with 188Re- HSA microspheres. ConclusionsThe method of 188Re(I)-tricarbonyl ion labeled HSA microspheres can proceed with high labeling yield. Furthermore, this method provided a convenient method for radio-labeling of HSA microspheres with 188Re as well as a kit for manufacturing.

Preparation of uniform-sized hemoglobin–albumin microspheres as oxygen carriers by Shirasu porous glass membrane emulsification technique

We have developed a new type of artificial oxygen carrier composed of bovine hemoglobin (bHb) and bovine serum albumin (BSA) prepared by Shirasu porous glass (SPG) membrane emulsification technique. The resultant emulsion droplets containing 10wt% bHb and 5–20wt% BSA were subsequently cross-linked by glutaraldehyde to form the microspheres. Due to the uniform pore structure of SPG membranes, the average diameters of bHb10–BSAm microspheres were successfully controlled at around 5μm with a coefficient of variation of around 10%. In addition, the biocompatibility of the carriers depended on their oxyhemoglobin percentage regardless of their same size. Finally, the P50 values of these microspheres ranged from 8.08 to 11.60mmHg, which showed a high oxygen affinity and an oxygen delivery function.

The effect of antisense to NF-κB in an albumin microsphere formulation on the progression of left-ventricular remodeling associated with chronic volume overload in rats

Background: Increased NF-κB levels play a crucial role in the pathophysiology of heart failure and are known to cause ventricular remodeling. Antisense therapy can be used for blocking the expression of NF-κB and subsequently avoiding heart failure. However, as with most biotechnology products, molecular instability and overall cost are often the major issues and concerns limiting the advancement of most antisense drugs to the market. Therefore, a cost-efficient biodegradable sustained release particle drug delivery system to transport and target NF-kB antisense to its intended site of action would be ideal.Purpose: To evaluate the in vivo performance of a sustained release spray-dried albumin microsphere formulation for effective delivery and treatment of left ventricular remodeling with antisense to NF-κB.Methods: Albumin-based microspheres encapsulating antisense to NF-kB were prepared by spray drying and studied in a rat model to treat congestive heart failure.Results: The NF-κB activation and TNF-α release seen in treated animals were significantly lower than control animals. Ventricular remodeling was controlled in animals with antisense-treated AV fistulas as ΔV0–25 and ΔV0 were significantly lower compared to animals with untreated AV fistulas.Conclusion: This treatment was successful in curbing ventricular remodeling by suppressing NF-κB activation.

Formulation and characterization of albumin microspheres containing norcantharidate for liver tumor targeting

The objectives of this study were first to encapsulate norcantharidate into albumin microspheres by the emulsion crosslinking method and second to characterize the microspheres in terms of the morphological examination, particle size, and encapsulation efficiency. The in vitro release of norcantharidate from the microspheres was studied by using the dialysis bag method. Pharmacokinetics and biodistribution studies were used to evaluate the advantages of microspheres than the conventional formulations. The microspheres prepared by crosslink emulsion were with uniform size, smooth surface, spherical shape, and disperse evenly. The particle size was uniform (13.3 ± 0.4 µm) and the encapsulation efficiency was 54.3 ± 4.18%. In vitro release indicated that the norcantharidate microspheres had a well-sustained release efficacy and fitted Korsmeyer’s Peppas release model. In vivo studies showed that pharmacokinetics of norcantharidate microspheres could be described by the model of two-compartment after i.v. administration and had higher AUC inside liver and spleen than the injection group. No histological change occurred to the rat liver after the administration of norcantharidate microspheres.

Selective internal radiation therapy of hepatic tumours: Is coiling of the gastroduodenal artery always beneficial?

To assess the effect of gastroduodenal artery (GDA) occlusion prior to selective internal radiation therapy (SIRT) with regards to arterial hepato-intestinal collateralization (HIC). Six hundred and six patients were scheduled for SIRT between 2006 and 2012 at University Hospital Essen, Germany. Digital subtraction angiography (DSA) followed by administration of 99m-technetium labelled human serum albumin microspheres ((99m)Tc-HSAM) and single-photon emission computed tomography combined with computed tomography (SPECT/CT) was initially performed. Depending on vascular anatomy and hepatic tumour load, GDA coil embolization was considered. In subsequent (99m)Tc-HSAM rescans or therapeutic DSA, HIC and its consequences for SIRT were analysed. The GDA was occluded in 86 of 606 patients (14%). Twenty-two of these 86 patients did not undergo SIRT due to the patients' clinical status or SIRT contraindications. In 28 of the remaining 64 patients, newly apparent or reopened HIC were seen either at the site of the proximal GDA (n = 21) or in the periphery of the hepatic arteries (n = 7). In 25 of these 28 patients, the HIC could be occluded or the catheter position could be changed achieving a safe (90)Y application. However, due to the newly visible HIC in three of 28 patients, SIRT was regarded as unsafe and was abandoned. Coil embolization of the GDA may induce arterial hepato-intestinal collaterals. Although most of these collaterals do not impede (90)Y administration, SIRT may become unfeasible in specific occasions. Hence, segmental or lobar SIRT instead of a whole-liver approach with coiling of the GDA is recommended.

Pharmacokinetic Characteristics of the Radiopharmaceutical “188Re-Albumin Microspheres” After Intravenous Administration to Laboratory Animals

Studies of the pharmacokinetics of 188Re-human serum albumin microspheres (MSA) of diameter 10 – 20 μm in intact mice showed that the maximum accumulation of activity (about 70%) 5 min at after intravenous administration was in the lungs. Elimination of activity from the lungs over the period 5 min to 3 h was about 7%. Over a period of 72 h, the quantity of 188Re-MSA in the lungs decreased approximately twofold. Prolonged retention of 188Re-MSA in the lungs could be explained in terms of the high stability of the chemical bond between 188Re and MSA. This was confirmed in control experiments of the pharmacokinetics of free 188Re as Na188ReO4. Results on the pharmacokinetic characteristics of 188Re-MSA provided evidence that this material may be useful for the radionuclide therapy of tumors in different locations after intravascular administration.

Initial study of radiological and clinical efficacy radioembolization using 188Re-human serum albumin (HSA) microspheres in patients with progressive, unresectable primary or secondary liver cancers.

BackgroundThe aim of this initial study was to evaluate the clinical and radiological effectiveness of radioembolization (RE) using 188Re-Human Serum Albumin (HSA) microspheres in patients with advanced, progressive, unresectable primary or secondary liver cancers, not suitable to any other form of therapy.Material/MethodsOverall, we included 13 patients with 20 therapy sessions. Clinical and radiological responses were assessed at 6 weeks after therapy, and then every 3 months. The objective radiological response was classified according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 by sequential MRI. Adverse events were evaluated using NCI CTCAE v.4.03.ResultsThere were 4 patients with hepatocellular carcinoma (HCC), 6 with metastatic colorectal cancer (mCRC), 2 with neuroendocrine carcinoma (NEC), and 1 patient with ovarian carcinoma. Mean administered activity of 188Re HSA was 7.24 GBq (range 3.8–12.4) A high microspheres labeling efficacy of over 97±2.1% and low urinary excretion of 188Re (6.5±2.3%) during first 48-h follow-up. Median overall survival (OS) for all patients was 7.1 months (CI 6.2–13.3) and progression-free survival (PFS) was 5.1 months (CI 2.4–9.9). In those patients who had a clinical partial response (PR), stable disease (SD), and disease progression (DP) as assessed 6 weeks after therapy, the median OS was 9/5/4 months, respectively, and PFS was 5/2/0 months, respectively. The treatment adverse events (toxicity) were at an acceptable level. Initially and after 6 weeks, the CTC AE was grade 2, while after 3 months it increased to grade 3 in 4 subjects. This effect was mostly related to rapid cancer progression in this patient subgroup.ConclusionsThe results of this preliminary study indicate that RE using 188Re HSA is feasible and a viable option for palliative therapy in patients with extensive progressive liver cancer. It was well tolerated by most patients, with a low level of toxicity during the 3 months of follow-up.

Layer-by-layer multienzyme assembly for highly sensitive electrochemical immunoassay based on tyramine signal amplification strategy

A new sandwich-type electrochemical immunosensor based on nanosilver-doped bovine serum albumin microspheres (Ag@BSA) with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for quantitative monitoring of biomarkers (carcinoembryonic antigen, CEA, used in this case) by coupling enzymatic biocatalytic precipitation with tyramine signal amplification strategy on capture antibody-modified glassy carbon electrode. Two immunosensing protocols (with and without tyramine signal amplification) were also investigated for the detection of CEA and improved analytical features were acquired with tyramine signal amplification strategy. With the labeling method, the performance and factors influencing the electrochemical immunoassay were studied and evaluated in detail. Under the optimal conditions, the electrochemical immunosensor exhibited a wide dynamic range of 0.005–80ngmL−1 toward CEA standards with a low detection limit of 5.0pgmL−1. Intra- and inter-assay coefficients of variation were below 11%. No significant differences at the 0.05 significance level were encountered in the analysis of 6 clinical serum specimens and 6 spiked new-born cattle serum samples between the electrochemical immunoassay and the commercialized electrochemiluminescent immunoassay method for the detection of CEA.

In vitro and ex vivo characterization of lectin-labeled Mycobacterium tuberculosis antigen-containing microspheres for enhanced oral delivery

Purpose: Oral immunization for mucosal protection against Mycobacterium tuberculosis would be the best option for effective tuberculosis (TB) control. However, this route of vaccine delivery is limited due to the short residence time of the delivery system at the site of absorption. Cytoadhension has made it possible to optimize the targeted delivery of oral vaccine to lymphoid tissues. The purpose of this project was to evaluate the ability of human M-cell specific lectin-labeled microparticles to target the human M-cells of the Peyer’s patches.Method: Albumin microspheres containing Mycobacterium tuberculosis cell lysate antigens were coupled with Wheat germ agglutinin and Aleuria aurantia lectins and their ability to bind to M cell models as well as their preferential distribution in the Peyer’s patches were investigated.Results: The study demonstrated an enhanced delivery of targeted polystyrene and BSA/Lysate microspheres to M cells. It was demonstrated that alpha-l-fucose sugar residue might be the target of these lectins.Conclusion: It can be concluded from the study that the lectin-coupled microspheres had better affinity for M-cells and showed preferential binding to the Peyer’s patches. This means that the coupling enhanced the targeted delivery of the antigens to the M cells.

Simultaneous dual-isotope SPECT/CT with 99mTc- and 111In-labelled albumin microspheres in treatment planning for SIRT

To investigate simultaneous dual-isotope SPECT/CT with two differently radioisotope-labelled albumin-microsphere fractions for treatment planning of hepatic radioembolisation. In addition to (99m)Technetium-labelled albumin microspheres (commercially available), we performed labelling with (111)Indium. Binding stability of (111)Indium-labelled microspheres was tested in vitro and in vivo in mice. Simultaneous dual-isotope SPECT/CT imaging was validated in an anthropomorphic torso phantom; subsequently, dual-isotope SPECT/CT was performed under in-vivo conditions in pigs (n = 3) that underwent transarterial injection of (99m)Technetium- and (111)Indium-labelled microspheres in the liver (right and left hepatic artery, respectively), in both kidneys and in the gluteal musculature. In total, n = 18 transarterial injections were performed. In-vitro testing and in-vivo studies in mice documented high binding stability for both (99m)Technetium-labelled and (111)Indium-labelled microsphere fractions. In phantom studies, simultaneous dual-isotope SPECT/CT enabled reliable separation of both isotopes. In pigs, the identified deposition of both isotopes could be accurately matched with intended injection targets (100 %, 18/18 intended injection sites). Furthermore, an incidental deposition of (99m)Technetium-labelled microspheres in the stomach could be correlated to the test injection into a right hepatic artery. Simultaneous dual-isotope SPECT/CT after transarterial injection with (99m)Technetium- and (111)Indium-labelled microspheres is feasible. Thus, it may offer additional, valuable information compared to single (99m)Technetium-labelled albumin examinations. • Simultaneous dual-isotope SPECT/CT with (111) In- and (99m) Tc-labelled albumin microspheres is feasible. • Differentiation of two microsphere fractions after transarterial injection is possible. • The origin of an extra-hepatic microsphere deposition can be correlated to the corresponding artery. • This technique could reduce the setup time for selective internal radiation treatment.

Characterization and Pharmacokinetic Evaluation of Gamma Sterilized Ketorolac Tromethamine Loaded Albumin Microspheres for Intramuscular Administration

Pharmacokinetic parameters of ketorolac tromethamine (KT) loaded albumin (KTAL) microspheres were determined using New Zealand white rabbits. Each rabbit (n=6) was injected 5 mg/kg body weight of plain KT or an equivalent dose in microsphere form in 2 mL water for injection. Prior to animal studies microspheres were tested for toxic residues and were gamma sterilized. Sterilized microspheres were evaluated for their integrity by physico-chemical characterization. Test for toxic residues was negative, the sterilization process utilized was effective and did not alter any physicochemical characteristics and showed good syringeability. When KT was administered in the form of microspheres there was a significant increase in Cmax, AUC, t1/2 and MRT (P < 0.05). When administered as microspheres, plasma concentration of drug sustained for 24 hours. It was concluded that KTAL microsphere formulation improved the systemic exposure and sustained the drug release and could be used for once-a-day administration of KT.

Gadolinium Oxide Nanoparticles as Potential Multimodal Imaging and Therapeutic Agents

Potentials of hydrophilic and biocompatible ligand coated gadolinium oxide nanoparticles as multimodal imaging agents, drug carriers, and therapeutic agents are reviewed. First of all, they can be used as advanced T1 magnetic resonance imaging (MRI) contrast agents because they have r1 larger than those of Gd(III)-chelates due to a high density of Gd(III) per nanoparticle. They can be further functionalized by conjugating other imaging agents such as fluorescent imaging (FI), X-ray computed tomography (CT), positron emission tomography (PET), and single photon emission tomography (SPECT) agents. They can be also useful for drug carriers through morphology modifications. They themselves are also potential CT and ultrasound imaging (USI) contrast and thermal neutron capture therapeutic (NCT) agents, which are superior to commercial iodine compounds, air-filled albumin microspheres, and boron ((10)B) compounds, respectively. They, when conjugated with targeting agents such as antibodies and peptides, will provide enhanced images and be also very useful for diagnosis and therapy of diseases (so called theragnosis).

Preparation and in vitro characterization of mucoadhesive Norethisterone - egg albumin microspheres for nasal administration.

In this study suitable, smooth, spherical, cross-linked egg albumin microspheres in the size range of 15-40 um loaded with norethisterone were prepared by multiple emulsion (o/w/o) method by the glutarldehyde cross-linking and thermal denaturation technique. Microspheres were prepared by using different drug/polymer ratios. Egg albumin was used as a mucoadhesive polymer in the formulation to increase the residence time of the microspheres on the nasal mucosa. The albumin microspheres were characterized and evaluated with respect to the particle size, production yield, encapsulation efficiency, shape and surface properties, drug polymer interaction, mucoadhesive property and suitability for nasal drug delivery. The in vitro diffusion of NE from the prepared microspheres exhibited the extent of drug release decreased from 95 –60%. The release of the drug has been controlled by swelling control release mechanism. No initial burst release has been recorded except for NE microspheres stabilized using 25% w/v glutarldehyde as cross-linking agent. The drug release from NE microspheres obeys Higuchi diffusion controlled model.

Microencapsulation of protein into biodegradable matrix: a smart solution cross-linking technique

Sustained-release albumin microspheres (MSs) can be obtained by chemically cross-linking albumin. However, a significant challenge is preventing the cross-linking of the active pharmaceutical (protein or small molecule) ingredient (API) with the MS matrix. To prevent cross-linking of the API with the albumin matrix, a smart “solution cross-linking-microencapsulation” method was developed which involves cross-linking albumin solution with glutaraldehyde first, neutralizing any excess glutaraldehyde with sodium bisulphite, followed by the addition of API and finally spray drying. Using lysozyme as model API, MS formulations FL1 and FL2 were prepared and characterized. Physicochemical characterization using FT-IR and bioactivity evaluation indicate that microencapsulated API did not undergo any significant change in its native structure and the bioactivity was preserved during the formulation processing. Preliminary immunogenicity potential of the cross-linked albumin matrix determined by in vivo studies did not show any significant increase in antigen-specific serum-IgG levels, implying safety and biocompatibility of the cross-linked albumin matrix.

Antibody modified Bovine Serum Albumin microspheres for targeted delivery of anticancer agent Gemcitabine

Inhibition of the EGFR signaling pathway is one of the attractive therapeutic targets for pancreatic cancer as recent studies demonstrated that EGFR is over‐expressed in pancreatic cancer. In this article we have demonstrated the design of targeted drug delivery system containing Bovine Serum Albumin (BSA) microspheres as delivery vehicle, gemcitabine as anticancer drug and anti‐EGFR (epidermal growth factor receptor) monoclonal antibody as targeting agent. The conjugated BSA microspheres were characterized by several physico‐chemical techniques such as scanning electron microscope, optical microscopy, fluorescent microscopy etc. Administration of these BSA microspheres containing gemcitabine and anti‐EGFR (BSA‐Gem‐EGFR) shows significant inhibition of pancreatic cancer cells (AsPC1) compared to the cells treated with only BSA microspheres, BSA with gemcitabine (BSA‐Gem), and free gemcitabine. This strategy could be used as a generalized approach for the treatment of pancreatic cancer along with other cancers which overexpress EGFR on cell surface. Copyright © 2012 John Wiley &amp; Sons, Ltd.