Properties Of Drug Delivery Systems Research Articles

Adsorption and Release Properties of Drug Delivery System Naproxen-SBA-15: Effect of Surface Polarity, Sodium/Acid Drug Form and pH.

Mesoporous silica SBA-15 was prepared via sol-gel synthesis and functionalized with different types of organosilanes containing various organic functional groups: (3-aminopropyl)triethoxysilane (SBA-15-NH2), (3-mercaptopropyl)triethoxysilane (SBA-15-SH), triethoxymethylsilane (SBA-15-CH3), triethoxyphenylsilane (SBA-15-Ph), and (3-isocynatopropyl)triethoxysilane (SBA-15-NCO). The prepared materials were investigated as drug delivery systems for naproxen. As model drugs, naproxen acid (HNAP) and its sodium salt (NaNAP) were used. Mentioned medicaments belong to the group of non-steroidal anti-inflammatory drugs (NSAIDs). The prepared materials were characterized by different analytical methods such as transmission electron microscopy (TEM), infrared spectroscopy (IR), nitrogen adsorption/desorption analysis (N2), thermogravimetric analysis (TG), 1H, 13C and 23Na solid-state nuclear magnetic resonance spectroscopy (1H, 13C and 23Na ss-NMR). The abovementioned analytical techniques confirmed the successful grafting of functional groups to the SBA-15 surface and the adsorption of drugs after the impregnation process. The BET area values decreased from 927 m2 g-1 for SBA-15 to 408 m2 g-1 for SBA-15-NCO. After drug encapsulation, a more significant decrease in surface area was observed due to the filling of pores with drug molecules, while the most significant decrease was observed for the SBA-15-NH2 material (115 m2 g-1 for NaNAP and 101 m2 g-1 for HNAP). By combining TG and nitrogen adsorption results, the occurrence of functional groups and the affinity of drugs to the carriers' surface were calculated. The dominant factor was the volume of functional groups and intermolecular interactions. The highest drug affinity values were observed for phenyl and amine-modified materials (SBA-15-Ph = 1.379 μmol m-2 mmol-1 for NaNAP, 1.761 μmol m-2 mmol-1 for HNAP and SBA-15-NH2 = 1.343 μmol m-2 mmol-1 for NaNAP, 1.302 μmol m-2 mmol-1 for HNAP) due to the formation of hydrogen bonds and π-π interactions, respectively. Drug release properties and kinetic studies were performed at t = 37 °C (normal human body temperature) in different media with pH = 2 as simulated human gastric fluid and pH = 7.4, which simulated a physiological environment. Determination of drug release quantity was performed with UV-VIS spectroscopy. The surface polarity, pH and naproxen form influenced the total released amount of drug. In general, naproxen sodium salt has a higher solubility than its acid form, thus significantly affecting drug release from surface-modified SBA-15 materials. Different pH conditions involved surface protonation and formation/disruption of intermolecular interactions, influencing both the release rate and the total released amount of naproxen. Different kinetic models, zero-order, first-order, Higuchi and Hixson-Crowell models, were used to fit the drug release data. According to the obtained experimental results, the drug release rates and mechanisms were determined.

Design of Experiment Approach to Modeling the Effects of Formulation and Drug Loading on the Structure and Properties of Therapeutic Nanogels.

The physical properties of nanoparticles may affect the uptake mechanism, biodistribution, stability, and other physicochemical properties of drug delivery systems. This study aimed to first develop a model exploring the factors controlling the nanogel physical properties using a single drug (propranolol), followed by an evaluation of whether these models can be applied more generally to a range of drugs. Size, polydispersity, ζ potential, and encapsulation efficiency were investigated using a design of experiment (DOE) approach to optimize formulations by systematically identifying the effects of, and interactions between, parameters associated with nanogel formulation and drug loading. Three formulation factors were selected, namely, chitosan concentration, the ratio between the chitosan and cross-linker—sodium triphosphate—and the ratio between the chitosan and drug. The results indicate that the DOE approach can be used not only to model but also to predict the size and polydispersity index (PDI). To explore the application of these prediction models with other drugs and to identify the relationship between the drug structure and nanogel properties, nanogels loaded with 12 structurally distinct drugs and 6 structurally similar drugs were fabricated at the optimal condition for propranolol in the model. The measured size, PDI, and ζ potential of the nanogels could not be modeled using distinct DOE parameters for dissimilar drugs, indicating that each drug requires a separate analysis. Nevertheless, for drugs with structural similarities, various linear and nonlinear trends were observed in the size, PDI, and ζ potential of nanogels against selected molecular descriptors, indicating that there are indeed relationships between the drug molecular structure and the performance outcomes, which may be modeled and predicted using the DOE approach. In conclusion, the study demonstrates that DOE models can be applied to model and predict the influence of formulation and drug loading on key performance parameters. While distinct models are required for structurally unrelated drugs, it was possible to establish correlations for the drug series investigated, which were based on polarity, hydrophobicity, and polarizability, thereby elucidating the importance of the interactions between the drug and the nanogels based on the nanogel properties and thus deepening the understanding of the drug-loading mechanisms in nanogels.

Physicochemical Characterization of Hyaluronic Acid and Chitosan Liposome Coatings

Hyaluronic acid (HA) and chitosan (CH) are biopolymers that are widely used in many biomedical applications and for cosmetic purposes. Their chemical properties are fundamental to them working as drug delivery systems and improving their synergistic effects. In this work, two different protocols were used to obtain zwitterionic liposomes coated with either hyaluronic acid or chitosan. Specifically, the methodologies used to perform vesicle preparation were chosen by taking into account the specific chemical properties of these two polysaccharides. In the case of chitosan, liposomes were first synthesized and then coated, whereas the coating of hyaluronic acid was achieved through lipidic film hydration in an HA aqueous solution. The size and the zeta-potential of the polysaccharide-coated liposomes were determined by dynamic light scattering (DLS). This approach allowed coated liposomes to be obtained with hydrodynamic diameters of 264.4 ± 12.5 and 450.3 ± 16.7 nm for HA- and CH-coated liposomes, respectively. The chemical characterization of the coated liposomal systems was obtained by surface infrared (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopies. In particular, the presence of polysaccharides was confirmed by the bands assigned to amides and saccharides being in the 1500–1700 cm−1 and 800–1100 cm−1 regions, respectively. This approach allowed confirmation of the efficiency of the coating processes, evidencing the presence of HA or CH at the liposomal surface. These data were also supported by time-of-flight secondary ion mass spectrometry (ToF-SIMS), which provided specific assessments of surface (3–5 nm deep) composition and structure of the polysaccharide-coated liposomes. In this work, the synthesis and the physical chemistry characterization of coated liposomes with HA or CH represent an important step in improving the pharmacological properties of drug delivery systems.

Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer.

Colorectal cancer is the third most common malignant disease worldwide, and chemotherapy has been the standard treatment for colorectal cancer. However, the therapeutic effects of chemotherapy are unsatisfactory for advanced and recurrent colorectal cancers. Thus, increasing the treatment efficacy of chemotherapy in colorectal cancer is a must. In this study, doxorubicin (DOX)-loaded tumor-targeting peptide-decorated mPEG-P(Phe-co-Cys) nanoparticles were developed to treat orthotopic colon cancer in mice. The peptide VATANST (STP) can specifically bind with vimentin highly expressed on the surface of colon cancer cells, thus achieving the tumor-targeting effects. The nanoparticles are core-shell structured, which can protect the loaded DOX while passing through the blood flow and increase the circulation time. The disulfide bonds within the nanoparticles are sensitive to the glutathione-rich microenvironment of tumor tissues. Rupture of disulfide bonds of the nanoparticles leads to the continuous release of DOX, thus resulting in the apoptosis of the tumor cells. The in vivo experiments in mice with orthotopic colon cancer demonstrated that the synthesized DOX-loaded tumor-targeting peptide-decorated polypeptide nanoparticles showed properties of drug delivery systems and exhibited good antitumor properties. The synthesized nanoparticles show appropriate properties as one of the drug delivery systems and exhibit good antitumor properties after encapsulating DOX.

Sterilization process of polyester based anticancer-drug delivery systems.

Recently, growing interest in biodegradable polyesters as drug carriers in the development of innovative anticancer drug delivery systems (DDSs) has been observed. These compounds are thermally unstable, and are therefore, particularly demanding due to the limited number of available sterilization techniques. Furthermore, the DDSs sterilization process is often limited to aseptic filtration. Ensuring aseptic production is very demanding and costly, and it is therefore necessary to work on the application of new sterilization methods. In view of this, this review presents the current state of knowledge regarding the radiation sterilization process of some anticancer drugs as well biodegradable polyester carriers (such as polylactide, polyglycolide, poly(ε-caprolactone), poly(trimethylene carbonate) and co- or terpolymers of lactide, glycolide, ε-caprolactone and trimethylene carbonate). The structural changes in anticancer DDSs under the influence of ionizing radiation and the potential degradation mechanisms of both, polyester carriers and cytostatics during the sterilization process of ionizing radiation as well as their effects on the microstructure and properties of DDSs have been discussed in this paper.

Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo

Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.

Pharmacokinetic and Pharmacodynamic Properties of Drug Delivery Systems.

The use of drug delivery systems (DDS) is an attractive approach to facilitate uptake of therapeutic agents at the desired site of action, particularly when free drug has poor pharmacokinetics/biodistribution (PK/BD) or significant off-site toxicities. Successful translation of DDS into the clinic is dependent on a thorough understanding of the in vivo behavior of the carrier, which has, for the most part, been an elusive goal. This is, at least in part, due to significant differences in the mechanisms controlling pharmacokinetics for classic drugs and DDSs. In this review, we summarize the key physiologic mechanisms controlling the in vivo behavior of DDS, compare and contrast this with classic drugs, and describe engineering strategies designed to improve DDS PK/BD. In addition, we describe quantitative approaches that could be useful for describing PK/BD of DDS, as well as critical steps between tissue uptake and pharmacologic effect.

Validation of Size Estimation of Nanoparticle Tracking Analysis on Polydisperse Macromolecule Assembly

As the physicochemical properties of drug delivery systems are governed not only by the material properties which they are compose of but by their size that they conform, it is crucial to determine the size and distribution of such systems with nanometer-scale precision. The standard technique used to measure the size distribution of nanometer-sized particles in suspension is dynamic light scattering (DLS). Recently, nanoparticle tracking analysis (NTA) has been introduced to measure the diffusion coefficient of particles in a sample to determine their size distribution in relation to DLS results. Because DLS and NTA use identical physical characteristics to determine particle size but differ in the weighting of the distribution, NTA can be a good verification tool for DLS and vice versa. In this study, we evaluated two NTA data analysis methods based on maximum-likelihood estimation, namely finite track length adjustment (FTLA) and an iterative method, on monodisperse polystyrene beads and polydisperse vesicles by comparing the results with DLS. The NTA results from both methods agreed well with the mean size and relative variance values from DLS for monodisperse polystyrene standards. However, for the lipid vesicles prepared in various polydispersity conditions, the iterative method resulted in a better match with DLS than the FTLA method. Further, it was found that it is better to compare the native number-weighted NTA distribution with DLS, rather than its converted distribution weighted by intensity, as the variance of the converted NTA distribution deviates significantly from the DLS results.

Biomaterials for local drug delivery in central nervous system

The central nervous system (CNS) is a vital part of human body which coordinate the actions by transmitting signals. Because of the existence of the blood-brain barrier and the blood-spinal cord barrier, diseases in CNS can hardly be directly intervened by non-invasive methods. While systemic delivery usually requires extravagant drug dosage and leads into toxicity in unexpected tissues, local drug delivery in CNS tissues provides a solution for the problems of physiological barriers and systematic side effects. Biomaterials are applied in local drug delivery system (LDDS) for CNS disease therapy with aims of tuning the drug release property and improving bioavailability, solubility, stability and safety of pharmaceutics. The indispensable importance and distinct physiological structure of cerebrospinal area bring about challenges to biomaterials in LDDS. Thus, properties of drug delivery systems are necessitated with prudently concern. In this review, the development of LDDS utilizing biomaterials will be presented, including sustained release, local parameter-responsible release, and regional cell-selective active targeting release. Studies on biomaterials employed as pharmaceuticals will give rise to a more efficacious method and the better understanding of LDDS design in CNS.

Advancements in macromolecular complexity and their implications for drug delivery systems

Background: Nanomaterials have revolutionized drug delivery systems, offering enhanced efficacy, reduced side effects, and improved patient compliance. Recent advancements in nanomedicine have focused on increasing macromolecular complexity to develop more sophisticated therapeutic options. Aim: This review explores the evolution of nanotherapeutics, from simple linear structures to complex branched and hyperbranched architectures and examines their implications for future drug delivery systems. Methods: The review discusses various nanocarriers, including liposomes, polymeric nanocarriers, and colloidal suspensions, emphasizing the role of macromolecular complexity in improving drug delivery efficacy. Key chemical techniques for synthesizing these macromolecules, such as controlled radical polymerization and click chemistry, are also analyzed. Results: Advances in synthetic polymer chemistry have enabled the development of diverse macromolecular structures that enhance drug loading, stability, and controlled release. Liposomal technology, although highly effective, faces challenges such as drug leakage and immune response, leading to the exploration of synthetic polymers like PLGA and polymeric micelles. These innovations have improved the pharmacokinetic properties of drug delivery systems. Conclusion: Increasing macromolecular complexity in drug delivery systems holds significant potential for overcoming physiological barriers, optimizing therapeutic outcomes, and fulfilling the demand for multifunctional nanomedicine.

Simulating copolymeric nanoparticle assembly in the co-solvent method: How mixing rates control final particle sizes and morphologies

The self-assembly of copolymeric vesicles and micelles in micromixers is studied by External Potential Dynamics (EPD) simulations – a dynamic density functional approach that explicitly accounts for the polymer architecture both at the level of thermodynamics and dynamics. Specifically, we focus on the co-solvent method, where nanoparticle precipitation is triggered by mixing a poor co-solvent into a homogeneous copolymer solution in a micromixer. Experimentally, it has been reported that the flow rate in the micromixers influences the size of the resulting particles as well as their morphology: At small flow rates, vesicles dominate; with increasing flow rate, more and more micelles form, and the size of the particles decreases. Our simulation model is based on the assumption that the flow rate mainly sets the rate of mixing of solvent and co-solvent. The simulations reproduce the experimental observations at an almost quantitative level and provide insight into the underlying physical mechanisms: First, they confirm an earlier conjecture according to which the size control takes place in the earliest stage of the particle self-assembly, during the spinodal decomposition of polymers and solvent. Second, they reveal a crossover between different morphological regimes as a function of mixing rate. Hence they demonstrate that varying the mixing rate in a co-solvent setup is an effective way to control two key properties of drug delivery systems, their mean size and their morphology.

Investigation of thermodynamic and structural properties of drug delivery system based on carbon nanotubes as a carboplatin drug carrier by molecular dynamics simulations

Drug delivery is an important application of nanotechnology, in particular the targeted delivery of anticancer drugs using carbon nanotubes. To investigate the anticancer carboplatin’s drug delivery system based on single-walled carbon nanotubes (SWCNTs), molecular dynamic (MD) simulations were applied to carboplatin filling inside pristine SWCNT and wrapping outside the pristine and functionalized SWCNT, and the drug in the free state. No significant difference was observed in the drug conformation in the free form in comparison to complex states with SWCNT. Situating carboplatin inside the pristine nanotube close to the end of the tube is an important option for releasing the drug. The typical motion of the drug outside the pristine SWCNT was along the end to one-third of the tube length, whereas carboxylic group on functionalized SWCNT kept the drug in the tube’s centerline. In addition, our energy analysis determined that the lowest binding free energy belongs to filling carboplatin in the SWCNT, resulting from the van der Waals interactions. MD simulations in comparison to previous experimental evidence confirm that the suitable model for a platinum-based anticancer drug delivery system based on SWCNTs is the encapsulation of these drugs inside nanotubes.

ASAXS Study on Spatial Distribution of Hydrophobic Compounds in Polymer Micelles

In drug delivery system (DDS) using polymer micelles as drug carrier, DDS properties are related to spatial distribution of drug compounds in the micelles [1]. Because the spatial distribution of drug compounds should strongly depend on interactions and solubility of drug compounds in the micelles, elucidation of the relation between chemical structures of drug compounds and their spatial distribution in the micelle is much important. Thus, in this study, we examine to elucidate the relation between chemical features and spatial distribution of drug compounds in polymer micelles by using anomalous small-angle X-ray scattering (ASAXS). To apply the ASAXS near bromine K-edge for analysis [2] of spatial distribution of drug compounds in polymer micelles, we employ 4 different bromine-labeled hydrophobic compounds as model drug compounds and polymer micelles composed of poly(dimethylaminoethyl methacrylate)-block-poly(methyl methacrylate) (PDMAEMA-b-PMMA). Figure shows SAXS and resonant term obtained from ASAXS near bromine K-edge for the polymer micelles containing 9-bromofluorene (BrF). The domain size estimated from the resonant term is much smaller than that of hydrophobic PMMA core of the micelle. Therefore, When BrF, which is highly hydrophobic and scarcely dissolved in hydrophobic PMMA, is incorporated in the polymer micelle, BrF forms small droplet in the hydrophobic core composed of PMMA. For the micelles incorporating bromobenzene, which as similar properties of BrF, similar result is obtained. On the other hand, 4-bromobenzyl alcohol and ethyl 2-bromoethyl propionate, which are miscible with PMMA, are homogeneously dispersed in the PMMA core of the micelles. These results indicate that highly hydrophobic compounds forms small droplet in hydrophobic core, and introduction of polarity to the compounds causes expansion of the area existing the hydrophobic compounds in polymer micelle.

Phospholipids in pulmonary drug delivery

Pulmonary delivery is becoming the standard route of administration for treating respiratory disorders such as asthma and chronic obstructive pulmonary disease. It is also gaining interest for non‐invasive systemic delivery of peptides and proteins. A limited number of excipients is approved or authorized for the pulmonary tract. This restricts the commercial potential of some formulations. Phospholipids and more particularly 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC) are the main components of lung surfactant and are recognized as generally recognized as safe (GRAS) excipients for pulmonary drug delivery by the Food and Drug Administration. Moreover, phospholipids could modulate the physicochemical properties of drug delivery systems and therefore the drug release and/or dissolution. They can potentially modulate the drug pharmacokinetic by enhancing the drug permeability through the lung epithelium using palmitoyl‐based phospholipids, and/or by reducing recognition of the drug delivery systems by the alveolar macrophages by including DPPC or polyethyleneglycol (PEG) at their surface. Therefore, this review focuses on the formulations containing phospholipids or PEGylated phospholipids, such as micelles, liposomes, lipid micro‐/nanoparticles, large porous particles, solid dispersions, and microparticle suspensions.Drug delivery systems composed mainly or secondarily by phospholipids could be aerosolized by an appropriate device (nebulizer for aqueous‐based formulations, pressurized metered dose inhalers for propellant or aqueous‐based formulations or dry powder inhaler for powder‐based formulations) to be deposited in the lungs following their aerodynamic diameter. Phospholipids included in the drug delivery systems could modulate aerodynamic performances and drug pharmacokinetic.

Pharmacokinetics and Biodistribution of Paclitaxel–Gelatin Nanoparticles

ABSTRACT Nanoscale manipulation of properties of drug delivery systems (DDSs) provides improved control over the pharmacokinetics and pharmacodynamics of encapsulated drugs relative to free drugs. This article summarizes the preparation and therapeutic applications of paclitaxel–gelatin nanoparticles (PGNs) (Type B, 75 Bloom) in the size range ∼150 to 200 nm as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), with ∼45% entrapment efficiency. Dose-dependent antineoplasticity in hepatocarcinoma, HepG2 cell line, was observed up to 72 h of incubation with PGN and the drug per se (<1 (g) showed 65% toxicity within 24 h). A pharmacokinetics and biodistribution study with endpoints at 2, 6, 24, and 48 h performed in normal and tumor-bearing, inbred Balb-c mice showed accumulation in liver and tumor with PGN. Enhanced paclitaxel accumulation in kidney was observed. In vivo antineoplastic studies showed an approximately threefold reduction of tumor with PGN.

Theranostic Nanomedicine

Nanomedicine formulations aim to improve the biodistribution and the target site accumulation of systemically administered (chemo)therapeutic agents. Many different types of nanomedicines have been evaluated over the years, including for instance liposomes, polymers, micelles and antibodies, and a significant amount of evidence has been obtained showing that these submicrometer-sized carrier materials are able to improve the balance between the efficacy and the toxicity of therapeutic interventions. Besides for therapeutic purposes, nanomedicine formulations have in recent years also been increasingly employed for imaging applications. Moreover, paralleled by advances in chemistry, biology, pharmacy, nanotechnology, medicine and imaging, several different systems have been developed in the last decade in which disease diagnosis and therapy are combined. These so-called (nano) theranostics contain both a drug and an imaging agent within a single formulation, and they can be used for various different purposes. In this Account, we summarize several exemplary efforts in this regard, and we show that theranostic nanomedicines are highly suitable systems for monitoring drug delivery, drug release and drug efficacy. The (pre)clinically most relevant applications of theranostic nanomedicines relate to their use for validating and optimizing the properties of drug delivery systems, and to their ability to be used for pre-screening patients and enabling personalized medicine. Regarding the former, the combination of diagnostic and therapeutic agents within a single formulation provides real-time feedback on the pharmacokinetics, the target site localization and the (off-target) healthy organ accumulation of nanomedicines. Various examples of this will be highlighted in this Account, illustrating that by non-invasively visualizing how well carrier materials are able to deliver pharmacologically active agents to the pathological site, and how well they are able to prevent them from accumulating in potentially endangered healthy tissues, important information can be obtained for optimizing the basic properties of drug delivery systems, as well as for improving the balance between the efficacy and the toxicity of targeted therapeutic interventions. Regarding personalized medicine, it can be reasoned that only in patients which show high levels of target site accumulation, and which respond well to the first couple of treatment cycles, targeted therapy should be continued, and that in those in which this is not the case, other therapeutic options should be considered. Based on these insights, we expect that ever more efforts will be invested in developing theranostic nanomedicines, and that these systems and strategies will contribute substantially to realizing the potential of personalized medicine.

Developing synthetic mucosa-mimetic hydrogels to replace animal experimentation in characterisation of mucoadhesive drug delivery systems

Mucosa-mimetic polymeric hydrogels have been developed to replace the use of animal tissues as substrates for characterising mucoadhesive properties of drug delivery systems.

Formulation and evaluation the bioadhesive properties of drug delivery system based on PEGylated mucin matrices

Objective To formulate and evaluate the application of PEGylated mucin in oral bioadhesive drug (OBD) delivery system. Methods The bioadhesive strength of different formulation ratios of polyethylene glycol (PEG) and mucin was evaluated by tensiometry. Co polymer matrices containing mucin and PEG (PEGylated mucin) in the following ratios of 1:1 (A), 2:1 (B), 1:2 (C), 0:1 (D) and 1:0 (E) were prepared by co-precipitation. Microparticles were prepared from the matrices using a size reduction technique. Five different samples were prepared using direct mixtures in the appropriate solvenfs having mucin and PEG ratios of 1:1, 2:1, 1:2, 0:1, 1:0 and labeled as (A-E). The matrices were evaluated for their flow properties and the in vitro bioadhesion characteristics of the samples were examined. Results The range of flow rates of the matrices was 1.35–2.23 g/sec. The angle of repose was in the range of 37.3–39.9 degree. The bulk and tapped densities were within the ranges of 0.41–0.49. The Hausner's quotient (HQ) were 1.12, 1.24, 1.14, 1.25 and 1.2 for matrix batches A-E respectively, The bioadhesive strength of polymer matrices appeared to be directly related to amount of mucin. The order of bioadhesive strength is 2:1 > 1:1 > 1:0 > 1:2 > 0:1 of PEG: mucin in both simulated intestine fluid (SIF) and simulated gastrointestinal fluid (SGF). The physical properties of the micrometrics properties of the matrices were within the accepted values. Conclusions OBD preparation containing PEGylated mucin can be prepared by direct compression and be used in drug delivery to the oral cavity.

Evaluating the mucoadhesive properties of drug delivery systems based on hydrated thiolated alginate

Mucoadhesive polymers have been proposed as drug delivery carriers due to their ability to adhere to the mucus layer. A relatively new class of mucoadhesive polymers, termed thiomers, was suggested as an improved carrier capable of creating disulfide covalent bond with the mucus. Since the wet physiological environment is likely to cause any delivery system to adsorb water and arrive hydrated to its target, studying the performance of mucoadhesive systems in their hydrated form is of major importance. Model thiomer, alginate-thiol, were synthesized and characterized the product using Nuclear Magnetic Resonance (NMR), Fourier Transform Infra Red spectroscopy (FTIR). The swelling behavior was determined gravimetrically and found to be affected from the thiolation. Interactions between the alginate-thiol and mucin glycoproteins, which are believed to be an outcome of disulfide bonds, were verified using rheology experiments. Adhesion of hydrated tablets with different cross linking densities to porcine's fresh small intestine tissue were characterized using a Lloyd Tensile Machine. It was shown that the thiolation did not improve the adhesion properties of hydrated tablets. It appears that the benefit achieved by adding thiol group to the polymer in dry tablet form was flawed in hydrated form due to formation of inter-molecular disulfide junctions.

What Is Nanomedicine?

The central nervous system (CNS) is a vital part of human body which coordinate the actions by transmitting signals. Because of the existence of the blood-brain barrier and the blood-spinal cord barrier, diseases in CNS can hardly be directly intervened by non-invasive methods. While systemic delivery usually requires extravagant drug dosage and leads into toxicity in unexpected tissues, local drug delivery in CNS tissues provides a solution for the problems of physiological barriers and systematic side effects. Biomaterials are applied in local drug delivery system (LDDS) for CNS disease therapy with aims of tuning the drug release property and improving bioavailability, solubility, stability and safety of pharmaceutics. The indispensable importance and distinct physiological structure of cerebrospinal area bring about challenges to biomaterials in LDDS. Thus, properties of drug delivery systems are necessitated with prudently concern. In this review, the development of LDDS utilizing biomaterials will be presented, including sustained release, local parameter-responsible release, and regional cell-selective active targeting release. Studies on biomaterials employed as pharmaceuticals will give rise to a more efficacious method and the better understanding of LDDS design in CNS.