Polyester micro- and nanospheres for controlled drug delivery, nanomedicine and other biomedical applications: progress and challenges

Different medicaments (water-soluble vitamins), silver nanoparticles, selenium nanoparticles) have been successfully encapsulated into polyester micro and nanospheres thus creating nanoparticles with the various morphological characteristic. The crucial requirements for the controlled and balanced release of the medicament in the body are their ideal spherical shape and narrow size distribution. The size and shape of particles play the key role in their adhesion and interaction with the cell. Polymer degradation, also, plays a key role in medicament release from sustained release polyester systems, therefore in order to elucidate the mechanism governing release, it appears essential to analyze the in vitro degradation behavior of these devices. An integrated study of the nanosphere composition and structure was carried out by combining different techniques. In vitro degradation process and release tests, cytotoxicity, labeling polyester particles by 99mTc and biodistribution of PLGA nanoparticles without and with encapsulated medicament were examined

Polyester micro- and nanosized systems with therapeutic functionality

Among the families of synthetic polymers, polyesters are very attractive for various medical, pharmaceutical, industrial and other purposes. The major applications include drug delivery systems, tissue engineering applications, resorbable sutures, and orthopaedic fixation devices. Polyester, poly (lactide-co-glycolide) (PLGA) is a copolymer of poly lactic acid (PLA) and poly glycolic acid (PGA). PLGA is biocompatible and biodegradable copolymer whit tunable properties. It is approved by FDA and has been comprehensively studied for the development of different systems and materials for commercial use and in research. It is often used for preparing controlled drug delivery devices. PLGA polymer particles allow the encapsulation of the medicament within the polymer matrix, where the basic requirement for the controlled and balanced release of the medicament in the body is its ideal spherical shape and narrow distribution of their sizes. Until now, different active substances have been successfully encapsulated within PLGA polymer matrix thus creating micro or nanosized systems with sustained release and different functionalities. One example is simultaneously encapsulation of water-soluble antioxidant (ascorbic acid, vitamin C) and poly(L-glutamic acid)-capped silver nanoparticles (AgNpPGA), within PLGA particles. These PLGA/AgNpPGA/ascorbic acid microspheres have been examined in terms of structural characteristics, morphology, stability, in vitro degradation, antimicrobial activity, cytotoxicity and induction of intracellular reactive oxygen species. They have demonstrated synergistic effects i.e. effective antioxidative and, at the same time, prolonged antimicrobial activity

Chapter 11 – Polymeric micro- and nanoparticles for controlled and targeted drug delivery

Nanotechnology has great potential in the field of medicine and pharmacy because nano objects have comparable dimensions to biological entities. Polymer-based particles play an integral role as vehicles in the controlled delivery of different forms and types of active substances, such as anticancer drugs, antihypertensive and immunomodulatory agents, medical imaging contrast media, hormones, vitamins, and different macromolecules, such as nucleic acids (deoxyribonucleic acid, ribonucleic acid), proteins, antibodies, etc. The release of the active agent may be constant over a long period, it may be cyclic over a long period, or it may be triggered by the environment or other external events. The purpose behind controlling the drug delivery is to achieve more effective therapies while eliminating the potential for both under and overdosing. Other benefits of using controlled-delivery systems can include the maintenance of drug levels within a desired range, the need for fewer administrations, making optimal use of the drug in question, and increased patient compliance. This review article reports on obtaining polymeric micro- and nanoparticles with a special emphasis on obtaining polyester particles, the incorporation of different active substances within a polymer matrix, the degradation and release process of active substances from the polymeric particles, the physiochemical and biological properties of such obtained systems, as well as their application as drug-delivery systems.This is the accepted manuscript of the book chapter: Wu, T.-J., Chiu, H.-Y., Yu, J., Cautela, M.P., Sarmento, B., das Neves, J., Catala, C., Pazos-Perez, N., Guerrini, L., Alvarez-Puebla, R.A., Vranješ-Đurić, S., Ignjatović, N.L., 2018. Nanotechnologies for early diagnosis, in situ disease monitoring, and prevention, in: Nanotechnologies in Preventive and Regenerative Medicine. Elsevier, pp. 1–92. [https://doi.org/10.1016/B978-0-323-48063-5.00001-0

Influence of Different Degradation Medium on Release of Ascorbic Acid from PLGA Nano ans Microspheres

Poster presented at PHYSICAL CHEMISTRY 2008. 9th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Belgrade, September 24-26, 200

Poly(lactide-co-glycolide)-based Micro and Nanoparticles for the Controlled Drug Delivery of Vitamins

Controlled drug delivery systems and polymeric carriers have undergone significant development in recent years. Polymers like polylactides (PLA), polyglycolides (PGA), poly(lactide-co-glycolides) (PLGA), are approved by the World Health Organization (WHO) and Food and Drug Administration (FDA) as materials that can be used in medicine and pharmacy. Owing to their biodegradable nature, polymer materials, such as copolymer poly(DL-lactide-co-glycolide), are widely used in various medical applications; controlled release of delivering drugs, carriers in the tissue engineering, fixation of bone fractures, chirurgical strings, etc. Polymeric particles are used for the controlled delivery of several types of medicaments, including anticancer agents, antihypertensive agents, immunomodulatory drugs, hormones, vitamins and macromolecules, such as nucleic acid, proteins, peptides, antibodies, etc. Preparation of poly(lactide-co-glycolide) submicron spheres poses serious challenges. The present review attempts to address some important issues related to micro/nanoparticle-based delivery systems comprising poly(lactide-co-glycolide), with a special reference to PLGA for the controlled delivery of vitamins. A range of topics is discussed, including formulation aspects of micro- and nanoparticles, the effects of particle size and size distribution, most commonly used incorporation techniques, surface modification with stabilizers, surface functionalization, and factors affecting degradation and drug release rate.\ud \ud A post-print version of the article: Uskokovic, Dragan, and Magdalena Stevanovic. 2009. “Poly(lactide-Co-Glycolide)-Based Micro and Nanoparticles for the Controlled Drug Delivery of Vitamins.” Current Nanoscience 5 (1) (February 1): 1–14. doi:10.2174/157341309787314566

Synthesis and characterization of DLPLG nanoparticles for controlled delivery of water-soluble vitamins

Biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular poly (DL-lactide-co-glycolide) (DLPLG) nanoparticles have been studied for controlled released drug delivery. In this paper we are describing new method of obtaining the system for targeted and controlled delivery of the folic acid in the body. Folic acid (pteroyl-L-glutamic acid, vitamin B9) is a water-soluble vitamin essential in the human diet. It is an important cofactor in the synthesis of DNA and RNA, of dividing cells, particularly during pregnancy and infancy when there is an increase in cell division and growth. The DLPLG particles were obtained by chemical solvent/non-solvent method with PVP as a surfactant. The obtained DLPLG particles are non-agglomerated, uniform and with particles size in the submicron scale. The folic acid has been encapsulated into the polymer matrix by means of homogenization of the water and organic phases. The concentration of the folic acid in the water has been varied in order to obtain nanoparticles with different ratio of DLPLG and folic acid. The samples were characterized by Infrared Spectroscopy (IR) and Scanning Electron Microscopy (SEM)

Synthesis, characterization and degradation of poly(DL-lactide-co-glycolide) nanospheres containing ascorbic acid

Askorbinska kiselina (vitamin C) je izuzetno važan i organizmu neophodan vitamin. Ima ulogu reduktanta slobodnih radikala čime smanjuje oštećenja nastala oksidativnim stresom koji je uzrok ili pratilac mnogih bolesti. U organizmu se ne skladišti i vrlo brzo se iz njega izlučuje. Problem se sastoji u tome da se askorbinska kiselina lako dekonponuje u biološki neaktivna jedinjenja čime je upotreba askorbinske kiseline na polju medicine, farmakologije, kozmetologije veoma limitirana. Kopolimer poli(DL-laktid-ko-glikolid) (DLPLG ) se, pored ostalog, koristi za izradu sistema za kontrolisanu dostavu najrazličitijih klasa medikamenata. Pod medikamentima se podrazumevaju lekovi i druga terapeutska sredstva. Polimerne čestice DLPLG-a dozvoljavaju inkapsulaciju medikamenata unutar polimerne matrice a za njihovo kontrolisano i ravnomerno otpuštanje unutar organizma osnovni je zahtev idealna sferičnost čestica kao i uska raspodela njihovih veličina. Inkapsulacijom askorbinske kiseline u polimernu matricu poli(DL-laktid-ko-glikolida) (DLPLG) bilo bi potencijalno moguće prevazići hemijsku nestabilnost vitamina C kao i postići njegovu višu, efikasniju i ravnomerniju raspodelu u organizmu, tokom dužeg perioda vremena. U ovoj disertaciji je opisano dobijanje poli(DL-laktid-ko-glikolid) nanosfera korišćenjem fizičkohemijske metode rastvarač/nerastvarač i tehnike centrifugalnog procesiranja. Ispitan je uticaj različitih stabilizatora (polivinil alkohola, polivinil pirolidona) na morfološke karakteristike čestica DLPLG-a sa i bez inkapsulirane askorbinske kiseline. U polimernu matricu DLPLG-a su inkapsulirane različite koncentracije askorbinske kiseline homogenizacijom vodene i organske faze. Nanočestice DLPLG-a sa različitim sadržajem askorbinske kiseline imaju različite morfološke karakteristike, različit stepen uniformnosti, sferičnosti, aglomeracije kao i različite veličine. Izračunat je prinos čestica DLPLG-a sa i bez vitamina kao i efikasnost inkapsulacije vitamina u polimernu matricu DLPLG-a. Proces degradacije čestica DLPLG-a bez i sa askorbinskom kiselinom kao i otpuštanje askorbinske kiseline iz polimerne matrice DLPLG-a tokom degradacije je ispitivano u in vitro uslovima u različitim degradacionim medijumima (fiziloškom rastvoru i fosfatnom pufer rastvoru uz prisustvo azida). Karakterizacija uzoraka je radjena metodama infracrvene spektroskopije (IR), ultravioletne spektrofotometrije (UV-VIS), diferencijalne skanirajuće kalorimetrije (DSC), skenirajuće elektronske mikroskopije (SEM) a radjena je i detaljna stereološka analiza.Ascorbic acid (vitamin C) is essential for preserving optimal health and it is used by the body for many purposes. Ascorbic acid acts as a reductant for many free radicals, thereby minimising the damage caused by oxidative stress which is a root cause of, or at least associated with, many diseases. Ascorbic acid is water soluble vitamin, which cannot be synthesised and stored in the body.The problem is that ascorbic acid easily decomposes into biologically inactive compounds making its use very limited in the field of pharmaceuticals, dermatologicals and cosmetics. Copolymer poly(DL-lactide-co-glycolide) (DLPLG) is among other things used for the controlled delivery of the various classes of medicaments. Under medicaments we assume drugs and other therapeutically applications. DLPLG polymer particles allow the encapsulation of the medicament within the polymer matrix, where the principle requirement for the controlled and balanced release of the medicament in the body is its ideal spherical shape and narrow particle size distribution. By encapsulating the ascorbic acid into the polymeric matrix it is assumed that its chemical instability can be overcame as well as higher, more efficient and equally distributed concentration throughout extended period of time can be achieved. This disertation is describing the process of obtaining poly(DL-lactide-co-glycolide) (DLPLG) nanospheres using physico-chemical method with solvent/non-solvent systems where obtained solutions have been centrifuged. The influence of the different stabilizers (polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP)) on the morphological characteristics of DLPLG particles with and without ascorbic acid has been examined. The encapsulation of the ascorbic acid in the polymer matrix is performed by homogenization of water and organic phases. Nanoparticles of the copolymer DLPLG with the different content of the ascorbic acid have different morphological characteristics, i.e. variable degree of uniformity, agglomeration, sizes and spherical shaping. The particle yield of DLPLG with and without ascorbic acid has been calculated as well as the loading efficiency of the ascorbic acid into the polymer matrix DLPLG. The degradation of the nanospheres of DLPLG, DLPLG/ascorbic acid nanoparticles and release rate of the ascorbic acid were studied for eight weeks in different degradation medium (physiological solution (0.9% sodium chloride in water) and phosphate buffered saline). The samples have been characterized by Infrared Spectroscopy (IR), Ultraviolet Spectroscopy (UV), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) and Stereological analysis

Nanoparticles: Potential for Use to Prevent Infections

One of the major issues related to medical devices and especially urinary stents are infections caused by different strains of bacteria and fungi, mainly in light of the recent rise in microbial resistance to existing antibiotics. Lately, it has been shown that nanomaterials could be superior alternatives to conventional antibiotics. Generally, nanoparticles are used for many applications in the biomedical field primarily due to the ability to adjust and control their physicochemical properties as well as their great reactivity due to the large surface-to-volume ratio. This has led to the formation of a new research field called nanomedicine which can be defined as the use of nanotechnology and nanomaterials in diagnostics, imaging, observing, prevention, control, and treatment of diseases. For example, coverings or coatings based on nanomaterials are now seen as a promising strategy for preventing or treating biofilms formation on healthcare kits, implants, and medical devices. Toxicity, inappropriate delivery, or degradation of conventionally used drugs for the treatment of infections may be avoided by using nanoparticles without or with encapsulated/immobilized active substances. Most of the materials which are used and examined for the preparation of the nanoparticles with encapsulated/immobilized active substances or smart reactive nanomaterials with antimicrobial effects are polymers, naturally derived antimicrobials, metal-based and non-metallic materials. This chapter provides an overview of the current state and future perspectives of the nanoparticle-based systems based on these materials for prevention, control, or elimination of biofilm-related infections on urinary stents. It also addresses manufacturing conditions indicating the huge potential for the improvement of existing and development of new promising stent solutions

Preparation and Characterization of Poly(D,L-Lactide-co-Glycolide) Nanoparticles Containing Ascorbic Acid

This paper is covering new, simplistic method of obtaining the system for controlled delivery of the ascorbic acid. Copolymer poly (D,L-lactide-co-glycolide) (DLPLG) nanoparticles are produced using physical method with solvent/nonsolvent systems where obtained solutions were centrifuged. The encapsulation of the ascorbic acid in the polymer matrix is performed by homogenization of water and organic phases. Particles of the DLPLG with the different content of ascorbic acid have different morphological characteristics, that is, variable degree of uniformity, agglomeration, sizes, and spherical shaping. Mean sizes of nanoparticles, which contain DLPLG/ascorbic acid in the ratio 85/150%, were between 130 to 200 nm depending on which stereological parameters are considered (maximal diameters Dmax, feret X, or feret Y). By introducing up to 15% of ascorbic acid, the spherical shape, size, and uniformity of DLPLG particles are preserved. The samples were characterized by infrared spectroscopy, scanning electron microscopy, stereological analysis, and ultraviolet spectroscopy

Tailored preparation of nano and micro composites as new controlled bone drug delivery systems

Method of homogenous sonochemical principle for obtaining controlled forms of micro/nano particles of desired shapes, size and distribution, and solvent/nonsolvent method for obtaining spherical particles of polymer or polymer/ceramics composites with the encapsulated pharmacologically active agent for the treatment of bone tissue pathology, are methods developed in our laboratory for the production of nano and micro ceramic/polymer or polymer composite systems which can be potentially used as controlled bone drug delivery system. Method of homogenous sonochemical precipitation, by designing synthesis parameters like temperature, frequency, energy and ultrasonic field regime, and by applying appropriate solvents, enables producing desired forms and particle structures. Through this method calcium phosphate systems can be obtained, but also systems where calcium phosphate particles are coated with bioresorbable polymer with immobilized antibiotic. Physicochemical synthesis procedure in solvent/non-solvent method consists of initial dissolve of desired bioresorbable polymers and its homogenization, followed by encapsulation of the desired agents. Already produced pharmaceutically active compounds (ascorbic, folic acid, peroxidase, antibiotics, autologous plasma, etc.) can be encapsulated or different calcium phosphates used as fillers for the defected bone tissue. Micro, submicro and nano sized particles in deagglomeration form, optimal for the advanced application in bone engineering, are obtained through these preparation methods