Chapter 8 - Polymer-based nanoparticles as delivery systems for treatment and vaccination of tuberculosis

Microparticle delivery system is accepted as are reliable. Mean to delivery the drug to the target site with specificity,. The drug should be delivered to specific target site at a rate and concentration that provides optimum therapeutic efficacy and reducing the side effect to minimum. Microspheres are empty spherical particles, the particle size is less than 200 mm. Microspheres are free flowing powder consisting of natural and synthetic polymers. They have the potential controlled release drug. Polymers are the most important things of pharmaceutical drug delivery. There are many kind of polymers which varying the properties available those days for use in different pharmaceutical applications. Polymers use in the preparation of microspheres is the synthetic and natural polymers. Synthetic polymers are acrolein, poly anhydrides, methyl meth acrylate, lactides, and glycosides. Natural polymers are albumin, gelatin, collagen, agarose, chitosan, carragenene. Microspheres are the free flowing powders consist of protein and synthetic polymers having a particle size ranging from 1 ? 1000 micrometer. Microspheres are prepared by several techniques but the choice of method depends upon the drug. The polymers used and duration of action required. The evaluation parameters of microspheres are micromeritic properties particle size and shape, swelling index, tapped density, drug loading efficiency. In coming days by combining numerous other sceniorio, we will find the microspheres in novel drug delivery. Specifically in disease cell sorting diagnostics, gene and genetic materials, safe targeted and effective in vivo delivery and supplements a tiny interpretation of diseased organ and tissue in the body. Keywords: Microencapsulation, novel drug delivery, synthetic and natural polymers, duration of action.

Polymer scaffolds are increasingly ubiquitous in the field of tissue engineering in improving the repair and regeneration of damaged tissue. Natural polymers exhibit better cellular adhesion and proliferation than biodegradable synthetics but exhibit inferior mechanical properties, among other disadvantages. Synthetic polymers are highly tunable but lack key binding motifs that are present in natural polymers. Using collagen and poly(lactic acid) (PLA) as models for natural and synthetic polymers, respectively, an evaluation of the cellular response of embryonic mouse fibroblasts (NIH 3T3 line) to the different polymer types was conducted. The samples were analyzed using LIVE/DEAD™, alamarBlue™, and phalloidin staining to compare cell proliferation on, interaction with, and adhesion to the scaffolds. The results indicated that NIH3T3 cells prefer collagen-based scaffolds. PLA samples had adhesion at the initial seeding but failed to sustain long-term adhesion, indicating an unsuitable microenvironment. Structural differences between collagen and PLA are responsible for this difference. Incorporating cellular binding mechanisms (i.e., peptide motifs) utilized by natural polymers into biodegradable synthetics offers a promising direction for biomaterials to become biomimetic by combining the advantages of synthetic and natural polymers while minimizing their disadvantages.

Object: The objective of the present study was to investigate the effect of various concentrations of natural and synthetic polymers on in vitro drug release from sustained release matrix tablets. Materials and method: HPMC K4M and acacia gum were used as synthetic (hydrophilic) and natural (hydrophobic) polymers respectively. Diclofenac sodium was used as a model drug to study the in vitro release profile. Matrix tablets of Diclofenac sodium were fabricated by varying the concentrations of both natural and synthetic polymer via direct compression method. Result: The results of all evaluation parameters of the matrix tablet were within the acceptable limit. A significant difference was observed on in vitro drug release due to difference in polymers and their concentration. HPMC K4M in the concentration of 7% w/v showed 88.20 ± 0.056% cumulative drug release at the end of 10 h while the same concentration of acacia showed 85.22% ± 0.045%. The release mechanism of matrix tablet followed zero order release kinetics. The finding of current investigation clearly indicates that the synthetic polymer was given a more sustained release profile than natural polymer on varied concentration. Conclusion: On comparing in vitro release of optimized formulation with marketed preparation, it was concluded that F3 was found to be more efficient and promising than marketed preparation.

The potential of polymeric micelles constructed by coalescing natural and synthetic polymers for tuberculosis (TB) treatment was evaluated in this work. We designed a polymeric micelle to improve the delivery of anti-TB drugs (rifampicin [RF] and isoniazid [INH]). The polymeric core was synthesized in the following order: initially chitosan (CS) was grafted with polycaprolactone (PCL) to form CS-g-PCL followed by amide bond formation with maleic anhydride-isoniazid (MA-INH); finally, CS-g-PCL was conjugated with the MA-INH moiety to form the CS-g-PCL/MA-INH polymeric core. Another anti-TB drug, RF, was loaded onto CS-g-PCL/MA-INH through dialysis. The changes in the nature of functional groups and crystallinity were investigated by Fourier transform infrared spectroscopy and X-ray diffraction analysis, respectively. The shape and size of CS-g-PCL/MA-INH and RF-CS-g-PCL/MA-INH were analyzed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. The cumulative drug release profiles were measured by UV-visible spectrophotometry and HPLC analysis. The antimicrobial activity of the loaded micelles was evaluated by finding the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bacterial cell rupture analyses. The nontoxic nature of the micelles was assessed by ex vivo studies on U937 and L929 cell lines and erythrocytes by performing an MTT assay, apoptosis assay, and hemolysis assay. Ex vivo cellular uptake and in vivo internalization of the INH- and RF-containing micelles were tested on U937 cells and zebrafish using fluorescence microscopy analysis. All of the observations indicate that the multi-TB drug-loaded polymeric micelle is a safe and effective system for the delivery of anti-TB drugs without affecting the mycobactericidal activity.

The hepatitis B virus binds avidly to albumin polymers which in turn may mediate the initial binding of viral particles to the liver cell. However, the interaction of albumin polymers with the liver remains poorly characterized, and the possibility that hepatic binding reflects an artifact of polymerization with glutaraldehyde has not been excluded. We therefore characterized the binding of 125I-labeled natural and synthetic albumin polymers to suspensions of rat hepatocytes. Saturable binding was demonstrated for all preparations of monomeric and polymeric albumin studied. Glutaraldehyde-polymerized albumin (mean polymerization number = 15) bound much more avidly than naturally occurring albumin polymers (mostly dimers and trimers) or monomeric albumin. Competition between monomer and synthetic polymer was not observed. Reduction of free aldehyde groups on the synthetic polymer decreased nonsaturable binding without affecting saturable binding. Autoradiography confirmed binding of polyalbumin to hepatic parenchymal cells. Glutaraldehyde-polymerized ovalbumin, a protein unrelated to serum albumin, also bound hepatocytes saturably. We conclude that hepatic binding of synthetic albumin polymers is not due to residual aldehyde groups on the polymer and is much more avid than for natural polymer. This difference may reflect the higher degree of polymerization or chemical modification of the synthetic polymer. The hepatic binding sites for synthetic polymer appear distinct from those previously described for monomeric albumin and may not be specific for albumin.

Fibroblasts are important for the successful healing of deep wounds. However, the influence exerted by Cuticell, a natural polymer on fibroblasts and by the synthetic polymer, Suprathel, made of poly-L-lactic acid, is not sufficiently characterised. This study compared the survival and growth characteristics of human juvenile and adult dermal fibroblasts as well as murine fibroblast cell line L929, on a natural polymer with those of a synthetic polymer using different culture models. Murine, juvenile and adult human fibroblasts were seeded on both the natural and synthetic polymers using statical slide culture or the medium air interface and dynamical rotatory culture. Cell adherence, viability, morphology and actin cytoskeleton architecture were monitored for 1-7 days. Biomaterial permeability was checked with a previously established diffusion chamber. The majority of the murine and adult human fibroblasts survived in slide and rotatory cultures on both wound dressings. The fibroblasts seeded on the synthetic polymer exhibited phenotypically a typical spread shape with multiple cell adhesion sites earlier than those on the natural polymer. The highest survival rates in all tested fibroblast species over the entire observation time were detected in rotatory culture (mean: >70%). Nevertheless, it led to cell-cluster formation on both materials. In the medium air interface culture, few adult fibroblasts adhered and survived until the seventh day of culture on both the natural and synthetic polymers, and no viable juvenile and L929 fibroblasts could be found by day seven. Apart from a significant higher survival rate of L929 in slide culture on the natural polymer compared with the synthetic polymer at the end of the culturing period (p<0.0001), and a higher cell survival of L929 on the natural polymer in medium air interface culture, only minor differences between both materials were evident. This suggested a comparable cytocompatibility of both materials. Permeability testing revealed slightly higher permeance of the natural polymer compared with the synthetic polymer. Cell survival rates depended on the culture system and the fibroblast source. Nevertheless, the juvenile skin fibroblasts were the most sensitive. This observation suggests that wound dressings used in treating children should be tested beforehand with juvenile fibroblasts to ensure the dressing does not compromise wound healing. Future experiments should also include the response of compromised fibroblasts, for example, from burn patients.

The complexity of synthetic and natural polymers used in industrial and medical applications is expanding; thus, it becomes increasingly important to improve and develop methods for their molecular characterization. Free-solution capillary electrophoresis is a robust technique for the separation and characterization of both natural and synthetic complex charged polymers. In the case of polyelectrolytes, free-solution capillary electrophoresis is in the "critical conditions" (CE-CC): it allows their separation by factors other than molar mass for molar masses typically higher than 20000 g/mol. This method is thus complementary to size-exclusion chromatography (SEC). SEC is widely used to determine molar mass distributions and their dispersities. Utilizing CE-CC, an analogous calculation of dispersity based on the distributions of electrophoretic mobilities was derived and the heterogeneity of composition or branching in different polysaccharides or synthetic polymers was obtained in a number of experimental cases. Calculations are based on a ratio of moments and could therefore be compared to simulations of polymerization processes, in analogy to the work performed on molar mass distributions. Among four possible types of dispersity, the most precise values were obtained with the calculation analogous with the dispersity of molar mass distribution Mw/Mn. In addition, the dispersity value allows conclusions based on a single value: the closer the dispersity is to 1, the more homogeneous the polymer is in terms of composition or branching. This approach allows the analysis of dispersity of important molecular attributes of polymers other than molar mass and aims at improving the overall molecular characterization of both synthetic and natural polymers. The dispersity can also be monitored online while performing a chemical reaction within the CE instrument.

Advances in Drug Delivery

Poly (vinyl alcohol) and hyaluronic acid hydrogels as potential biomaterial systems - A comprehensive review

17 - Fabrication of Tissue Engineering Scaffolds

Vaccines are among the most important innovations in human history. The development and widespread implementation of vaccines over the past two centuries have saved billions of lives and have completely eliminated or dramatically reduced the global burden of diseases such as smallpox, polio and diphtheria. However, there remains an urgent and unmet need for vaccines against many diseases that have proven recalcitrant to traditional immunization approaches such as malaria, tuberculosis and HIV, which are collectively responsible for over 4.5 million deaths per year [1]. This challenge persists because vaccines, which have historically been based on killed or weakened forms of a microbe (e.g., virus or bacterium), often fail to elicit the correct type or magnitude of immune response to confer protective immunity. The need to achieve greater control over the magnitude and phenotype of an immune response has catalyzed a shift away from empirical vaccinology toward the rational design of vaccines founded upon a fundamental understanding of how the immune system combats infection. Toward this end, many modern vaccines combine recombinant protein antigens – to define the antigenspecificity of the response – with synthetic immunostimulatory molecules (adjuvants) that engage specific pattern recognition receptors (PRRs) – to generate an appropriate innate immune response to initiate and shape the adaptive response to the antigen. For example, the Cervarix human papillomavirus vaccine contains both recombinant virus like particles and monophosphoryl lipid A, an agonist of TLR-4 [2]. However, this shift toward developing successful synthetic vaccines is associated with several important drug delivery challenges. How can vaccines be delivered to the proper antigen presenting cells? How can vaccines be delivered to the proper pathways within these cell populations? How can vaccines be enriched within lymph nodes – the command centers of an immune response – while minimizing systemic distribution and the risk of potential adverse side effects? How can physicochemically diverse vaccine constituents be packaged and delivered to generate an optimal response? Polymeric delivery systems enable solutions to many of these challenges, and recent advances in polymer chemistry are poised to impact the future of vaccine delivery.

Functional hydrogels are used for numerous biomedical applications such as tissue engineering, wound dressings, lubricants, contact lenses and advanced drug delivery systems. Most of them are based on synthetic or natural polymers forming a three-dimensional network that contains aqueous media. Among synthetic polymers, poly(meth)acrylates, polyethyleneglycols, poly(vinylalcohols), poly(vinylpyrrolidones), PLGA and poly(urethanes) are of high relevance, whereas natural polymers are mainly polysaccharides such as hyaluronic acid, alginate or chitosan and proteins such as albumin, collagen or elastin. In contrast to most synthetic polymers, natural polymers are biodegradable. Both synthetic and natural polymers are often chemically modified in order to improve or induce favorable properties and functions like high mechanical strength, stiffness, elasticity, high porosity, adhesive properties, in situ gelling properties, high water binding capacity or drug release controlling properties. Within this review we provide an overview about the broad spectrum of biomedical applications of functional hydrogels, summarize innovative approaches, discuss the concept of relevant functional hydrogels that are in clinical trials and highlight advanced products as examples for successful developments.

Polymers play an important role as excipients in any dosage form. They influence drug release and should be stable, economic compatible, non-toxic, etc. They are broadly classified as natural polymers and synthetic polymers. Synthetic and natural based biodegradable polymers have received much more attention in the last decades due their potential applications in the fields related to environmental protection and the maintenance of physical health. Biodegradable materials are used in agriculture, medicine packaging, and other areas. In recent years there has been an increase in interest in biodegradable polymers. Two classes of biodegradable polymers can be distinguished: synthetic or natural polymers. Synthetic polymers are widely used in biomedical implants and devices because they can be fabricated into various shapes. Natural polymers are basically polysaccharides so they are biocompatible and without any side effects. In this chapter we have discussed various natural polymers, their advantages over synthetic polymers and role of natural polymers in designing novel drug delivery systems.

A review on versatile applications of blends and composites of CNC with natural and synthetic polymers with mathematical modeling

Most commercialized wound dressings are polymer-based. Synthetic and natural polymers have been utilized widely for the development of wound dressings. However, the use of natural polymers is limited by their poor mechanical properties, resulting in their combination with synthetic polymers and other materials to enhance their mechanical properties. Natural polymers are mostly affordable, biocompatible, and biodegradable with promising antimicrobial activity. They have been further tailored into unique hybrid wound dressings when combined with synthetic polymers and selected biomaterials. Some important features required in an ideal wound dressing include the capability to prevent bacteria invasion, reduce odor, absorb exudates, be comfortable, facilitate easy application and removal as well as frequent changing, prevent further skin tear and irritation when applied or removed, and provide a moist environment and soothing effect, be permeable to gases, etc. The efficacy of polymers in the design of wound dressings cannot be overemphasized. This review article reports the efficacy of wound dressings prepared from a combination of synthetic and natural polymers.