scholarly journals Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 91 ◽  
Author(s):  
Nadezhda Knauer ◽  
Ekaterina Pashkina ◽  
Evgeny Apartsin

Supramolecular chemistry holds great potential for the design of versatile and safe carriers for therapeutic proteins and peptides. Nanocarriers can be designed to meet specific criteria for given application (exact drug, administration route, target tissue, etc.). However, alterations in the topology of formulation components can drastically change their activity. This is why the supramolecular topology of therapeutic nanoconstructions has to be considered. Herein, we discuss several topological groups used for the design of nanoformulations for peptide and protein delivery: modification of polypeptide chains by host-guest interactions; packaging of proteins and peptides into liposomes; complexation and conjugation with dendrimers. Each topological type has its own advantages and disadvantages, so careful design of nanoformulations is needed. Ideally, each case where nanomedicine is needed requires a therapeutic construction specially created for that taking into account features of the administration route, target tissue, or organ, properties of a drug, its bioavailability, etc. The wide number of studies in the field of protein delivery by supramolecular and nanocarriers for proteins and peptides evidence their increasing potential for different aspects of the innovative medicine. Although significant progress has been achieved in the field, there are several remaining challenges to be overcome in future.

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 656 ◽  
Author(s):  
Shi Su ◽  
Peter M. Kang

Background: Nanomedicine is a field of science that uses nanoscale materials for the diagnosis and treatment of human disease. It has emerged as an important aspect of the therapeutics, but at the same time, also raises concerns regarding the safety of the nanomaterials involved. Recent applications of functionalized biodegradable nanomaterials have significantly improved the safety profile of nanomedicine. Objective: Our goal is to evaluate different types of biodegradable nanomaterials that have been functionalized for their biomedical applications. Method: In this review, we used PubMed as our literature source and selected recently published studies on biodegradable nanomaterials and their applications in nanomedicine. Results: We found that biodegradable polymers are commonly functionalized for various purposes. Their property of being naturally degraded under biological conditions allows these biodegradable nanomaterials to be used for many biomedical purposes, including bio-imaging, targeted drug delivery, implantation and tissue engineering. The degradability of these nanoparticles can be utilized to control cargo release, by allowing efficient degradation of the nanomaterials at the target site while maintaining nanoparticle integrity at off-target sites. Conclusion: While each biodegradable nanomaterial has its advantages and disadvantages, with careful design and functionalization, biodegradable nanoparticles hold great future in nanomedicine.


2021 ◽  
Vol 10 (1) ◽  
pp. 57-66
Author(s):  
E. O. Bakhrushina ◽  
M. N. Anurova ◽  
N. B. Demina ◽  
I. V. Lapik ◽  
A. R. Turaeva ◽  
...  

Introduction. Effective delivery of ophthalmic drugs is challenging. The eye has a number of protective systems and physiological barriers, which is why ophthalmic dosage forms have a low bioavailability, usually not exceeding 5 %. Topical drug administration is relatively easy to use and is most commonly prescribed by physicians for the treatment of ophthalmic diseases, especially the anterior segment of the eye. However, when using traditional delivery systems, a number of problems arise: patients' violation of the drug administration technique, and, as a consequence, a decrease in treatment compliance, restriction of drug delivery to the target eye tissues due to low epithelial permeability and rapid clearance after drug administration. Maintaining a constant therapeutic drug level is another challenge that traditional delivery systems often fail to cope with.Text. The article discusses the types of ophthalmic delivery systems. Traditional ones are represented by such dosage forms as eye drops, ointments, gels. Modern ophthalmic dosage forms are represented by: eye films, contact lenses and eye implants. The characteristics, advantages and disadvantages of each type of delivery systems and their promising directions of development, as well as modern developments in this area are given.Conclusion. Currently, most of the scientific research on the development of ophthalmic delivery systems is devoted to obtaining dosage forms capable of maintaining a constant concentration of the drug in the target tissue, providing the transport of active ingredients to them. This is achieved by using modern advances in nanotechnology and polymer chemistry. Receive liquid and soft dosage forms with micro-, nano- and micro-nano-carriers. Polymeric delivery systems such as films, lenses and implants are being actively developed and studied. The development of modern technological approaches opens up new possibilities for the treatment of a wide range of ophthalmic diseases by reducing the side effects often induced by the intrinsic toxicity of molecules, reducing the frequency of the administered dose and maintaining the pharmacological profile of the drug. Thus, the use of modern ophthalmic delivery systems can significantly limit the use of invasive treatments.


Author(s):  
Carmine D’Amico ◽  
Flavia Fontana ◽  
Ruoyu Cheng ◽  
Hélder A. Santos

AbstractThe current situation, heavily influenced by the ongoing pandemic, puts vaccines back into the spotlight. However, the conventional and traditional vaccines present disadvantages, particularly related to immunogenicity, stability, and storage of the final product. Often, such products require the maintenance of a “cold chain,” impacting the costs, the availability, and the distribution of vaccines. Here, after a recall of the mode of action of vaccines and the types of vaccines currently available, we analyze the past, present, and future of vaccine formulation. The past focuses on conventional formulations, the present discusses the use of nanoparticles for vaccine delivery and as adjuvants, while the future presents microneedle patches as alternative formulation and administration route. Finally, we compare the advantages and disadvantages of injectable solutions, nanovaccines, and microneedles in terms of efficacy, stability, and patient-friendly design. Graphical abstract Different approaches to vaccine formulation development, the conventional vaccine formulations from the past, the current development of lipid nanoparticles as vaccines, and the near future microneedles formulations are discussed in this review. 


Author(s):  
Mehta Abhinav ◽  
Jain Neha ◽  
Grobler Anne ◽  
Vandana Bharti

Novel drug delivery systems (NDDS) are one of the most strategies which enable to overcome the problems related to drug bioavailability. It is the rate and extent to which a drug becomes available to the target tissue after its administration. Most of the new drugs used today have poor bioavailability and are required to be administered at higher doses because only a small fraction of the administered dose is absorbed in the systemic circulation and able to reach the target site. This results in the wastage of major amount of drug and lead to adverse effects. Pharmaceutical technology mainly focuses on enhancing the solubility and permeability of drugs with lower bioavailability. Nanotechnology is the concept used in NDDS that enables a weight reduction of drug particles accompanied by an increase in stability and improved functionality. Various approaches such as nanosuspensions, liposomes, niosomes, nanoemulsions, cubosomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), cyclodextrins, phytosome etc., are used for the enhancement of bioavailability. The present review focuses on the different approaches used for bioavailability enhancement along with their advantages and disadvantages.


Author(s):  
R.A. Galicia-Gonzalez ◽  
M.E. Ortega-Cerrilla ◽  
C. Nava-Cuellar ◽  
L. Miranda-Jiménez ◽  
M. Ramírez-Mella ◽  
...  

Objective: To review different nanoparticle sterilization methods for their use in biomedical applications in animals. Approach: Sterilization is used to obtain a microorganism-free product without altering its physicochemical characteristics during its preparation, storage, or administration route. This review explores different sterilization methods and their advantages and disadvantages on the nanoparticle level. Study limitations/implications: Nanoparticles are used in animal production, including their parenteral administration. Therefore, establishing the characteristics of different technologies applied to sterilize nanoparticles is essential to ensure the delivery of sterile products preventing health risks. Conclusions: The use of nanotechnology in livestock production offers several advantages for animal nutrition, reproduction, and health, among other things. When nanoparticles must be sterilized, choosing the most suitable method is essential. This depends on the amount of product and its compound type because each technique has specific requirements that must be taken into account to be ready for potential changes in the structure and availability of the final product.


Author(s):  
Mara Heckmann ◽  
Gerald Klanert ◽  
Georg Sandner ◽  
Peter Lanzerstorfer ◽  
Manfred Auer ◽  
...  

Abstract Postprandial insulin-stimulated glucose uptake into target tissue is crucial for the maintenance of normal blood glucose homeostasis. This step is rate-limited by the number of facilitative glucose transporters type 4 (GLUT4) present in the plasma membrane. Since insulin resistance and impaired GLUT4 translocation are associated with the development of metabolic disorders such as type 2 diabetes, this transporter has become an important target of antidiabetic drug research. The application of screening approaches that are based on the analysis of GLUT4 translocation to the plasma membrane to identify substances with insulinomimetic properties has gained global research interest in recent years. Here, we review methods that have been implemented to quantitate the translocation of GLUT4 to the plasma membrane. These methods can be broadly divided into two sections: microscopy-based technologies (e.g., immunoelectron, confocal or total internal reflection fluorescence microscopy) and biochemical and spectrometric approaches (e.g., membrane fractionation, photoaffinity labeling or flow cytometry). In this review, we discuss the most relevant approaches applied to GLUT4 thus far, highlighting the advantages and disadvantages of these approaches, and we provide a critical discussion and outlook into new methodological opportunities.


Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6816
Author(s):  
Sanja Milkovska-Stamenova ◽  
Michele Wölk ◽  
Ralf Hoffmann

Sample preparation is the most critical step in proteomics as it directly affects the subset of proteins and peptides that can be reliably identified and quantified. Although a variety of efficient and reproducible sample preparation strategies have been developed, their applicability and efficacy depends much on the biological sample. Here, three approaches were evaluated for the human milk and plasma proteomes. Protein extracts were digested either in an ultrafiltration unit (filter-aided sample preparation, FASP) or in-solution (ISD). ISD samples were desalted by solid-phase extraction prior to nRPC-ESI-MS/MS. Additionally, milk and plasma samples were directly digested by FASP without prior protein precipitation. Each strategy provided inherent advantages and disadvantages for milk and plasma. FASP appeared to be the most time efficient procedure with a low miscleavage rate when used for a biological sample aliquot, but quantitation was less reproducible. A prior protein precipitation step improved the quantitation by FASP due to significantly higher peak areas for plasma and a much better reproducibility for milk. Moreover, the miscleavage rate for milk, the identification rate for plasma, and the carbamidomethylation efficiency were improved. In contrast, ISD of both milk and plasma resulted in higher miscleavage rates and is therefore less suitable for targeted proteomics.


2020 ◽  
Vol 21 (4) ◽  
pp. 334-343 ◽  
Author(s):  
Jiemin Wang ◽  
Junyong Wu ◽  
Yongjiang Li ◽  
Jing Wen ◽  
Jiaxin Cai ◽  
...  

: Therapeutic peptides (TPs) are biological macromolecules which can act as neurotransmitters, hormones, ion channel ligands and growth factors. Undoubtedly, TPs are crucial in modern medicine. But low bio-stability and some special adverse reactions reduce their places to the application. : With the development of nanotechnology, nanoparticles (NPs) in pharmaceutical science gained much attention. They can encapsulate the TPs into their membrane or shell. Therefore, they can protect the TPs against degradation and then increase the bioavailability, which was thought to be the biggest advantage of them. Additionally, targeting was also studied to improve the effect of TPs. However, there were some drawbacks of nano TPs like low loading efficiency and difficulty to manufacture. : Nowadays, lots of studies focused on improving effect of TPs by preparing nanoparticles. In this review, we presented a brief analysis of peptide-combined nanoparticles. Their advantages and disadvantages were listed in terms of mechanism. And several examples of applications were summarized.


2015 ◽  
Vol 51 (75) ◽  
pp. 14239-14242 ◽  
Author(s):  
Huaimin Wang ◽  
Youzhi Wang ◽  
Xiaoli Zhang ◽  
Yawen Hu ◽  
Xiaoyong Yi ◽  
...  

Supramolecular nanofibers of proteins and peptides could be used for intracellular protein delivery.


1969 ◽  
Vol 112 (5) ◽  
pp. 679-689 ◽  
Author(s):  
P. J. G. Butler ◽  
J. I. Harris ◽  
B S Hartley ◽  
R. Leberman

1. Maleic anhydride was shown to react rapidly and specifically with amino groups of proteins and peptides. Complete substitution of chymotrypsinogen was achieved under mild conditions and the extent of reaction could be readily determined from the spectrum of the maleyl-protein. 2. Maleyl-proteins are generally soluble and disaggregated at neutral pH. Trypsin splits the blocked proteins only at arginine residues and there is frequently selectivity in this cleavage, e.g. in yeast alcohol dehydrogenase and pig glyceraldehyde 3-phosphate dehydrogenase. 3. The group is removed by intramolecular catalysis at acid pH. The half-time was 11–12hr. at 37° at pH3·5 in ∈-maleyl-lysine or in maleyl-chymotrypsinogen. 4. The unblocking reaction can be used as the basis for a ‘diagonal’-electrophoretic separation of lysine peptides and N-terminal peptides, as shown by studies with β-melanocyte-stimulating hormone.


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