Petar D Petrov | Bulgarian Academy of Sciences (original) (raw)

Papers by Petar D Petrov

Molecules, 2021

Biopolymer materials have been considered a “green” alternative to petroleum-based polymeric mate... more Biopolymer materials have been considered a “green” alternative to petroleum-based polymeric materials. Biopolymers cannot completely replace synthetic polymers, but their application should be extended as much as possible, exploiting the benefits of their low toxicity and biodegradability. This contribution describes a novel strategy for the synthesis of super-macroporous 2-hydroxyethylcellulose (HEC) cryogels. The method involves cryogenic treatment of an aqueous solution of HEC and citric acid (CA), freeze drying, and thermally induced crosslinking of HEC macrochains by CA in a solid state. The effect of reaction temperature (70–180 °C) and CA concentration (5–20 mass % to HEC) on the reaction efficacy and physico-mechanical properties of materials was investigated. Highly elastic cryogels were fabricated, with crosslinking carried out at ≥ 100 °C. The storage modulus of the newly obtained HEC cryogels was ca. 20 times higher than the modulus of pure HEC cryogels prepared by phot...

Macromolecules, 2019

We introduce a "click" chemistry-based concept for the preparation of amphiphilic block copolymer... more We introduce a "click" chemistry-based concept for the preparation of amphiphilic block copolymers comprising linear polyglycidol (PG). Herein, a new class of linear polyglycidol/poly(ε-caprolactone) (PG/PCL) block copolymers of precisely designed macromolecular characteristics and composition was synthesized to demonstrate the convenience of this strategy. Monohydroxyl poly(ethoxyethylglycidyl ether) (PEEGE) precursors were synthesized by ring-opening anionic polymerization of ethoxyethylglycidyl ether (EEGE) and subsequently functionalized with a "clickable" alkyne end group. In parallel, a bifunctional PCL diol was modified to an azide-terminated macroreagent. PG/PCL block copolymers were obtained by "click" coupling reaction of the alkyn-and azide-functional macroreagents in the presence of a CuBr/PMDETA catalytic complex and subsequent cleavage of the protective ethoxyethyl groups of PEEGE. The amphiphilic block copolymers were not directly soluble in water, and defined nano-sized micelles were obtained via the solvent evaporation method. The synthesis pathway described here can be extended toward synthesis of various functional block copolymers comprising linear PG.

Advances in Polymer Science, 2014

Carbohydrate polymers, 2018

We report a novel approach for fabricating nanocomposite polysaccharide-based carriers for sustai... more We report a novel approach for fabricating nanocomposite polysaccharide-based carriers for sustained delivery of poorly-water-soluble drugs by embedding stabilized core-shell micelles (SPM) possessing hydrophobic cores into super-macroporous hydroxypropyl cellulose (HPC) cryogels. Firstly, nano-sized SPM were synthesized by loading and photochemical crosslinking of pentaerythritoltetraacrylate (PETA) in poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO19PPO29PEO19) core-shell micelles. Next, HPC cryogels containing different amount of SPM were fabricated by combination of cryogenic treatment and photo-crosslinking. A crosslinking agent, N,N'-methylenebisacrylamide, was used to enhance the density of polymer network. The effect of SPM concentration on gel fraction yield, swelling degree, cryogel morphology and mechanical properties were studied. Nanocomposite cryogels were loaded with curcumin and their encapsulation efficiency and drug release profile as a...

Pharmaceutics, 2022

We report the elaboration of redox-responsive functional micellar nanocarriers designed for trigg... more We report the elaboration of redox-responsive functional micellar nanocarriers designed for triggered release of caffeic acid phenethyl ester (CAPE) in cancer therapy. Three-layered micelles, comprising a poly(ε-caprolactone) (PCL) core, a middle poly(acrylic acid)/poly(ethylene oxide) (PAA/PEO) layer and a PEO outer corona, were prepared by co-assembly of PEO113-b-PCL35-b-PEO113 and PAA13-b-PCL35-b-PAA13 amphiphilic triblock copolymers in aqueous media. The preformed micelles were loaded with CAPE via hydrophobic interactions between the drug molecules and PCL core, and subsequently crosslinked by reaction of carboxyl groups from PAA and a disulfide crosslinking agent. The reaction of crosslinking took place in the middle layer of the nanocarriers without changing the encapsulation efficiency (EE~90%) of the system. The crosslinked polymeric micelles (CPMs) exhibited superior structural stability and did not release CAPE in phosphate buffer (pH 7.4). However, in weak acidic media a...

Polymer, 2002

Novel high molecular weight poly(ethylene oxide)-b-poly(alkylglycidyl ether) diblock copolymers h... more Novel high molecular weight poly(ethylene oxide)-b-poly(alkylglycidyl ether) diblock copolymers have been synthesized by sequential anionic-coordination polymerization using a calcium amide-alkoxide initiating system. The hydrophobic blocks were formed by polymerization of alkylglycidyl ethers differing in the size of the hydrophobe and the length of the oxyethylene spacer between the terminal hydrophobes and the polymerizable epoxy group. The length of the spacer was 0, 2 or 10 oxyethylene units. The content of the hydrophobic groups in the copolymers was about 2 wt% as determined by 1 H NMR and the molecular weights were found to be up to 1.8 £ 10 6 g/mol by using GPC and SLS. The aqueous solution properties of the copolymers were studied by static fluorescence, static and dynamic light scattering and transmission electron microscopy. The copolymers were found to self-associate in core-corona type particles in a relatively narrow concentration range. The aggregation numbers and the dimensions of the aggregates were determined by a combination of dynamic and static light scattering molecular weights. Core-corona nanoparticles of low aggregation number (3-5) and slightly extended coronae were found to coexist with unassociated macromolecules in the concentration range between the critical aggregation concentration and the overlap concentration. Both particles were visualized by TEM.

Langmuir, 2007

We report the synthesis and self-assembly of amphiphilic, nonspherical, polymeric microparticles.... more We report the synthesis and self-assembly of amphiphilic, nonspherical, polymeric microparticles. Wedge-shaped particles bearing segregated hydrophilic and hydrophobic sections were synthesized in a microfludic channel by polymerizing across laminar coflowing streams of hydrophilic and hydrophobic polymers using continuous flow lithography (CFL). Particle monodispersity was characterized by measuring both the size of the particles formed and the extent of amphiphilicity. The coefficient of variation (COV) was found to be less than 2.5% in all measured dimensions. Particle structure was further characterized by measuring the curvature of the interface between the sections and the extent of cross-linking using FTIR spectroscopy. The amphiphilic particles were allowed to selfassemble in water or at water-oil interfaces. In water, the geometry of the particles enabled the formation of micellelike structures, while in emulsions, the particles migrated to the oil-water interface and oriented themselves to minimize their surface energy.

ACS Omega, 2021

Niosomes are a type of vesicular nanocarrier exploited for enhancing the therapeutic efficacy of ... more Niosomes are a type of vesicular nanocarrier exploited for enhancing the therapeutic efficacy of various drugs in clinical practice. Niosomes comprise a bilayer hydrophobic membrane enclosing a central cavity filled with an aqueous phase, and therefore, they can encapsulate and deliver both hydrophobic and hydrophilic substances. Niosomal nanocarriers are preferred over other bilayer structures such as liposomes due to their chemical stability, biodegradability, biocompatibility, low production cost, low toxicity, and easy storage and handling. In addition, the niosomal membrane can be easy modified by the inclusion of ligands or stimulus-sensitive segments for achieving targeted delivery and triggered release of the encapsulated cargo. This mini-review outlines the current advances in designing functional niosomes and their use as platforms for developing advanced drug and gene delivery systems.

Proceedings of The International conference on innovative research in Science Engineering & Technology

In the past few years, graphene and graphene based materials have attracted great interest due to... more In the past few years, graphene and graphene based materials have attracted great interest due to their unique electronic, mechanical, optical, and thermal properties. Graphene oxide (GO) has all the advantages of graphene, but, unlike it, can be dispersed well in water. Polymeric cryogels are fascinating soft materials with wide applications in drug delivery, tissue engineering, chromatography, etc. Nanocomposite cryogel materials from natural polysaccharides and GO are attractive because they possess a set of favourable properties like biodegradability and biocompatibility, high porosity and water uptake, improved mechanical strength and electrical conductivity, and could broad the range of applications in the area of medicine and biotechnology. In this contribution we report on the fabrication of novel supermacroporous nanocomposite cryogels based on hydroxpropylcellulose (HPC) and graphene oxide by two different methods. The first method involves mixing of aqueous dispersion of GO and solution of HPC, freezing and photo-crosslinking. In this case, GO is embedded into the cryogel walls. In the second method, a pre-formed and lyophilized HPC cryogel is immersed in dispersion of GO and then frozen and lyophilized. Thus GO is deposited on the inner surface of cryogel. The second method allows the preparation of super-macroporous nanocomposites of a higher GO content, better control of physico-mechanical properties and enhanced electrical conductivity (3 orders of magnitude higher than pure HPC) as compared to the nanocomposite cryogels made by the first method.

Comptes Rendus De L Academie Bulgare Des Sciences, 2021

Coronavirus infectious disease 2019 (COVID-19), caused by the severe acute respiratory syndrome c... more Coronavirus infectious disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected all major aspects of society worldwide. Therefore, it is imperative to expedite the development of highly effective tools for reducing person-to-person virus transmission, effective treatment of patients and disease prevention. Huge efforts are being made on how to adapt the existing knowledge and speed up the transfer of our developments to help society tackle this global problem. In this regard, nanotechnology has offered vast opportunities to boost the fabrication of frontline tools against SARS-CoV-2. This review article discusses the advancement of nanotechnology in fabricating nanovaccines and antiviral nanoformulations, nanomaterial-based diagnostic platforms and personal protective equipment (PPE) for the fight with the new coronavirus. © 2021 Academic Publishing House. All rights reserved.

Macromolecular Chemistry and Physics

Polymers

In this contribution, we report the development of original nanocomposite cryogels for sustained ... more In this contribution, we report the development of original nanocomposite cryogels for sustained topical delivery of hydrophobic natural active substances such as cannabidiol (CBD). The cryogels were fabricated by a method involving cryogenic treatment and photo-crosslinking of aqueous systems containing biodegradable 2-hydroxyethyl cellulose (HEC) and CBD-loaded polymeric micelles. The preparation of the water-soluble form of CBD was a key element for the successful drug loading in the one-pot reaction. The main physical, mechanical and biological characteristics of CBD-loaded and blank cryogels such as gel fraction yield, swelling degree, morphology, storage and loss moduli, and cytotoxicity were studied in detail. The advantage of nanocomposite over pure HEC cryogel carriers in terms of achieving a sustained release profile was also demonstrated.

Biomaterials Science

Multifunctional micelles based on two co-assembled block copolymers are proven to effectively acc... more Multifunctional micelles based on two co-assembled block copolymers are proven to effectively accumulate and deliver curcumin in mitochondria, thus, inducing a much higher proapoptotic activity than single copolymer micelles.

Polish Journal of Microbiology, 2016

The capability of the biosurfactant-producing strain Rhodococcus wratislawiensis BN38 to minerali... more The capability of the biosurfactant-producing strain Rhodococcus wratislawiensis BN38 to mineralize both aromatic and aliphatic xenobiotics was proved. During semicontinuous cultivation 11 g/l phenol was completely degraded within 22 cycles by Rhodococcus free cells. Immobilization in a cryogel matrix was performed for the first time to enhance the biodegradation at multiple use. A stable simultaneous hydrocarbon biodegradation was achieved until the total depletion of 20 g/l phenol and 20 g/l n-hexadecane (40 cycles). The alkanotrophic strain R. wratislawiensis BN38 preferably degraded hexadecane rather than phenol. SEM revealed well preserved cells entrapped in the heterogeneous super-macroporous structure of the cryogel which allowed unhindered mass transfer of xenobiotics. The immobilized strain can be used in real conditions for the treatment of contaminated industrial waste water.

European Polymer Journal, 2016

Abstract Functional multilayer polymeric micelles were obtained by self-assembly of a poly(ethyle... more Abstract Functional multilayer polymeric micelles were obtained by self-assembly of a poly(ethylene oxide)- b -poly( n -butyl acrylate)- b -poly(acrylic acid) (PEO 113 - b -PnBA 235 - b -PAA 14 ) triblock terpolymer and exploited as template for the synthesis of silver nanoparticles and loading of anti-cancer agents. The terpolymer was synthesized by atom transfer radical polymerization of n -butyl acrylate and tert -butyl acrylate (tBA), initiated by a PEO-based macroinitiator. Then, PtBA blocks were converted into PAA by selective hydrolysis. PEO 113 - b -PnBA 235 - b -PAA 14 terpolymer formed nano-sized spherical micelles in the concentration range from 1 to 10 mg mL −1 as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The presence of PAA chains in the middle micellar layer allowed loading of silver ions and subsequent UV-induced synthesis of silver nanoparticles within the micelles. After that, the anti-cancer drug curcumin was loaded in the hydrophobic PnBA micellar cores. The effect of combination of two anti-cancer agents, spontaneously released from the micelles, on the vitality of acute myeloid leukemia (HL-60), its multidrug-resistant subline HL-60/DOX and human urinary bladder carcinoma (EJ) cells was assessed. The in vitro experiments revealed enhanced efficacy in regard to the cytotoxic activity of silver nanoparticles and curcumin.

Toxicology Mechanisms and Methods, 2016

To evaluate the safety profile of cationic micelles, based on triblock copolymer poly(dimethylami... more To evaluate the safety profile of cationic micelles, based on triblock copolymer poly(dimethylaminoethyl methacrylate)-poly(e-caprolactone)-poly(dimethylaminoethyl methacrylate) (PDMAEMA9- PCL70-PDMAEMA9), the effects of empty (PM) and curcumin loaded micelles (PM-Curc) on nonenzyme induced lipid peroxidation (LPO) in vitro, hemolytic activity and morphological changes in some organs after repeated intraperitoneal administration in vivo were studied. To induce LPO, rat liver microsomes were incubated with a solution of iron sulfate and ascorbinic acid (Fe(2+)/AA). The effect of empty PM (40 and 100 μg/ml), PM-Curc and free curcumin (both at 3.48 and 8.7 μg curcumin/ml) was assessed at 20 min incubation time. In the non-enzyme induced LPO model, the investigated substances at all concentrations significantly decreased the formation of malondialdehyde (MDA), compared to the Fe(2+)/AA induced LPO group. According to the results it can be concluded that curcumin alone and loaded in PM, exert significant antioxidant activity. In the biocompatibility safety studies, the mean hemolytic index for polymeric carrier was less than 2%, indicating it was non-hemolytic. The general appearance of the organ tissues from Wistar rats, treated in vivo with curcumin loaded PM was similar to that of controls, thus showing no apparent toxicity after repeated 14-days treatment.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, Jan 23, 2016

Polymeric micelles have attracted significant attention because of their potential application as... more Polymeric micelles have attracted significant attention because of their potential application as promising drug-delivery systems. In the present study cationic micelles, based on triblock copolymer poly(dimethylaminoethyl methacrylate) - poly(e-caprolactone) - poly(dimethylaminoethyl methacrylate) were prepared and loaded with curcumin. In vitro cytotoxicity of empty and curcumin loaded polymer micelles was investigated on two cell culture models, human hepatoma cell line HEP G2 and freshly isolated rat hepatocytes, following their viability and lactate dehydrogenase (LDH) leakage. MTT dye reduction assay and LDH release study showed that empty cationic micelles did not cause significant changes in cell viability and membrane integrity at the concentration range from 10.0 to 80.0 μg/ml. Our special attention was focused on the effects of empty and curcumin loaded micelles on oxidative stress markers malondialdehyde (MDA) and reduced glutathione (GSH). The increase in the micelles c...