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Introduction: Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation. Methods: Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed. Results: The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release. Conclusion: Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered.

Introduction: Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation. Methods: Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed. Results: The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release. Conclusion: Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered. [ABSTRACT FROM AUTHOR]

The novel polymeric particulate systems show high potential in their clinical effectiveness. Nevertheless, many of the drug delivery systems developed in the research laboratories have not found their way to clinics. The lack of therapeutic efficacy and safety, due to the use of some materials unapproved by the FDA, seems to be an important reason behind the unsuitability of the developed polymeric systems for the clinical application. Through specific design, choice of proper approach and excipients, the zero order linear release is highly achievable. The aim of this review was to explain the challenges associated with formulation development for several therapeutic agents in polymeric particulate system by scientific evidences. Growing interest in biotechnology and application of therapeutic proteins and peptides in various pathogenic disorders caused our special focus on their quality and preparation challenges. In this review, all formulation development issues i.e. choice of material, the amount of their use and regulatory policies were discussed. In the rest, other formulation development parameters such as effect of particle size, pH, drug loading as well as production method difficulties, dosage form qualities and route of administration to reach high quality particles were reviewed. Generally, this review tried to address an overview on how to solve the difficulties in the path of development of the polymeric particles for the pharmaceutical purposes. Formulation challenges in polymeric drug delivery carriers regarding encapsulation efficiency of drugs and release kinetics properties. Unlabelled Image • Drug loading and its release pattern are dependent on the preparation parameters. • Understanding the process variables avoids wasting of time and expensive materials. • To commercialize the polymeric particulate product, biopharmacy should be considered. [ABSTRACT FROM AUTHOR]

Integrins are cellular surface receptors responsible for the activation of many cellular pathways in cancer. These integrin proteins can be specifically targeted by small peptide sequences that offer the potential for the differentiation of cellular subpopulations by using magnetically assisted cellular sorting techniques. By adding a gold shell to the magnetic nanoparticles, these integrin-peptide interactions can be differentiated by surface-enhanced Raman spectroscopy (SERS), providing a quick and reliable method for on-target binding. In this paper, we demonstrate the ability to differentiate the peptide-protein interactions of the small peptides CDPGYIGSR and cyclic RGDfC functionalized on gold-coated magnetic nanoparticles with the integrins they are known to bind to using their SERS signal. SW480 and SW620 colorectal cancer cells known to have the integrins of interest were then magnetically sorted using these functionalized nanoparticles, suggesting differentiation between the sorted populations and integrin populations among the two cell lines.

Peptides and proteins have become very promising drug candidates in recent decades due to their unique properties. However, the application of these drugs has been limited by their high enzymatic susceptibility, low membrane permeability and poor bioavailability when administered orally. Considerable efforts have been made to design and develop drug delivery systems that could transport peptides and proteins to targeted area. Although it is of great importance to determine the composition after loading a drug to the carrier, the ability to do so is significantly limited by current analytical methods. In this letter, five important proteins, α 1 -antitrypsin, hemoglobin human, human serum albumin, human transferrin and r-globulin were chemically conjugated to two model drug carriers, namely carbon dots and polymer O-(2-carboxyethyl) polyethylene glycol. A simple yet convenient method based on circular dichroism spectroscopy was developed to determine the compositions of the various protein-carrier conjugates. [ABSTRACT FROM AUTHOR]

Since the first experiments in which high energy collision induced decomposition was used to determine structural information nearly fifty years ago, a variety of different methods of ion activation have been developed each of which has its own advantages and disadvantages. The development of “soft” ionisation techniques and their use to ionise biological species of very high molecular weights has resulted in ion activation techniques and tandem mass spectrometry becoming one of the most important fields of interest. Developments in mass analysers have also changed the emphasis placed on different activation techniques and opened up new opportunities and challenges. Although collision induced decomposition (CID) has been widely used, it has a number of drawbacks and new ion activation methods have been developed, the most widely used being electron capture decomposition (ECD) and electron transfer decomposition (ETD), each of which has its own particular advantages. Surface induced decomposition (SID) has been less widely adopted because it requires commercial instrumentation to be modified. Applications of these four techniques are discussed with special reference to peptide and protein sequencing. [ABSTRACT FROM AUTHOR]

Abstract: Microbial levans are biopolymers produced from sucrose-based substrates by a variety of microorganisms. There is very limited information related to the levan-based drug delivery systems. In this study, bovine serum albumin (BSA) encapsulated-levan nanoparticles were prepared using levan produced by a new Halomonas sp. Effects of polymer and BSA concentrations and rotating speed on in vitro characterization of the nanoparticles were investigated. The size of levan nanoparticles, with the surface charges +4.3mV to +7.6mV, changed between 200nm and 537nm. The encapsulation capacity of the particles changed between 49.3% and 71.3% depending on the levan concentration used in the formulation. The cumulative in vitro release of protein from the particles was shown to be controlled release of BSA. This study affirmed the suitability of levan by Halomonas sp. to be used as a nanocarrier system for potential delivery of macromolecular drugs such as peptides and proteins. [ABSTRACT FROM AUTHOR]

Abstract: Many methods were used to devise peptide and protein drugs delivery system (DDS). Because of their relatively large size, they have low transdermal bioavailabilities. In systemic delivery of proteins, biodegradable material as parenteral depot formulation occupy an important place because of several aspects like protection of sensitive proteins from degradation, prolonged or modified release, pulsatile release patterns. The main objective in developing controlled release protein injectables is avoidance of regular invasive doses which in turn provide patient compliance, comfort as well as control over blood levels. This review article presents the outstanding contributions in field of microencapsulation as protein delivery systems and different approaches of protein delivery are described. Then discusses how these advances may be applied to resolve the challenges face the development of microcapsule for the controllable delivery of protein drugs. [Copyright &y& Elsevier]

Proteomics by mass spectrometry (MS) allows for the identification of amino acid/peptide sequences in complex mixtures. Peptide analysis and quantitation enables screening of protein biomarkers and targeted protein biomarker analysis for clinical applications. Whereas miniature mass spectrometers have primarily demonstrated point-of-care analyses with simple procedures aiming at drugs and lipids, it would be interesting to explore their potential in analyzing proteins and peptides. In this work, we adapted a miniature MS instrument for peptide analysis. A mass range as wide as 100-2000 m / z was achieved for obtaining peptide spectra using this instrument with dual linear ion traps. MS 2 and MS 3 can be performed to analyze a wide range of peptides. The parameters of pressure, electric potentials, and solution conditions were optimized to analyze peptides with molecular weights between 900 and 1800 Da. The amino acid sequences were identified using both beam-type and in-trap collision-induced dissociation, and the results were comparable to those obtained by a commercial quadrupole time-of-flight mass spectrometer. With product ion monitoring scan mode, peptide quantitation was performed with a limit of detection of 20 nM achieved for the Met peptide. The method developed has also been applied to the analysis of the trypsin-digested cell lysate of SKBR3 cells with a low expression level of the Met gene.

The use of peptides and proteins in the pharmaceutical field has increased dramatically over recent years. They have been especially relevant to advances in the treatment of cancer, rheumatoid arthritis, leukemia, and cardiovascular, ophthalmological, metabolic, and infectious diseases. Despite the great potential of peptides and proteins, their use in pharmaceuticals has failed to reach its full potential because of some outstanding challenges. They are unstable under storage conditions and in biological milieus, and their high molecular weight limits permeation through biological membranes. A variety of delivery systems have been investigated to overcome these limitations. Polyelectrolytes (PEs) are molecules that bear multiple negative or positive charges. These molecules play an important role in various platforms relating to the delivery of peptide/protein-based drugs and subunit vaccines. The most commonly utilized PEs include chitosan, alginate, chondroitin sulfate, and poly(γ-glutamic acid). PE-based delivery systems, such as polyelectrolyte complexes (PECs), PE-coated nanocarriers, and PE multilayers, were designed to protect peptides and proteins from degradation and facilitate their absorption. These delivery systems are especially effective when administered orally or intranasally. This review emphasizes the important role of PEs and PE-based delivery vehicles in peptide/protein-based drugs and vaccines.