Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5932_Библиотеки_им_академика_М_И_Перельмана

Another major hurdle for GO in the pharmaceutical industry is its instability in water. As GO tends to collect in physiological uids like proteins and salt due to nonspecic binding and electrostatic interactions, it is difcult to use it as a build­ing block for biological probes [43]. By adding certain functional groups, GO can be made more physiologically soluble and hence more useful in biological settings. Moreover, GO is one of the most popular and extensively investigated nanomaterials for uses involving drug delivery due to its better features, including a higher surface area. Adistinct graphene derivative, reduced graphene oxide (rGO), is readily avail­able by thermal or chemical reduction of GO and has been used in various practical settings, including drug delivery [44].

8.2.4 hyDrogels

Fong et al. (2017) have created a folic acid (FA) conjugated GO nanocarrier (GO-FA) for the targeted delivery of DOX [59]. The drug-loaded nanocompos­ite (GO-FA-DOX) was included in the injectable and thermosensitive hyaluronic acid-chitosan-g-poly(N-isopropyl acrylamide) (HACPN) hydrogel for intratumoral drug administration. The HACPN hydrogel’s congurable breakdown time enables ne control of the DOX release when used with a GO-FA nanocarrier. Due to its high drug loading efciency and time-dependent toxicity impact in-vitro, GOFA-DOX/ HACPN has shown promise as a potential in-vivo treatment. Blood tests and major organ biopsies both revealed no signs of side effects, supporting the treatment’s safety [59]. In another work, Zhu etal. (2015) developed an injectable hydrogel composed of chitosan and glycerophosphate salt that increased the therapeutic efciency of DOX [60]. The chemotherapeutic drug DOX was preloaded into a super-paramagnetic graphene oxide (GO/IONP/PEI) gel via polyethyleneimine (PEI) modication. It has been demonstrated that DOX-GO/IONP/PEI has more cytotoxicity and anticancer activity than free DOX [60]. Its improved capacity to inltrate cell membranes was the cause of this.

For biodistribution and precise cell targeting, polymeric nanohybrid materials con­tain a biological surface modication, a therapeutic “payload,” and a core substance

[61]. Nanovector drug delivery systems, such as the anticancer drug paclitaxel, are used in biomedical applications to encapsulate and transport medications with low water solubility [62,63]. Abraxane, a drug marketed as paclitaxel coupled to albu­min nanoparticles, is an FDA-approved therapy for metastatic breast cancer [63]. Tumors can be noninvasively targeted with polymeric nanovectors. Nanohybrid materials facilitate drug delivery, imaging, and targeting. Polylactide-polyglycolide copolymers entrapping luteinizing hormone-releasing hormone (LHRH), marketed as goserelin (Zoladex) and leuprolide (Lupron Depot) and liposomes encapsulating daunorubicin and doxorubicin, marketed as DaunoXome and Doxil/Caelyx, have also received attention in cancer drug delivery [43,64]. Other polymers include poly­caprolactones, N-(2-hydroxyl propyl)methacrylamide (HPMA) copolymers, polygly­colic acid (PGA) containing paclitaxel (XyotaxTM), and natural polymers such as albumin, gelatin, alginate, collagen, and chitosan. Many studies have been conducted on polymer-drug conjugates [65].

Drug polymer conjugates increase a drug’s plasma half-life and tumor site accu­mulation because polymers have a greater hydrodynamic volume. Doxorubicin and PHPMA copolymer had drug stability in plasma of ve minutes when given sepa­rately but one hour when combined, increasing drug accumulation in solid tumors [66]. Antibodies, peptides, and saccharides are connected in the PHPMA copolymer [61]. HPMA-doxorubicin uses Galactosamine to target the hepatocyte asialoglyco­protein receptors [67]. Styrene maleic anhydride, in combination with neocarzinos­tatin (SMANCS), is used to treat hepatocellular cancer [68]. Targeting the treatment of tumor cells by receptor-mediated endocytosis is made possible by the conjugation of transferrin, folate, epidermal growth factor, and arginine-glycine-aspartic acid (RGD) tripeptide to the polymer backbone [61]. It is advisable to use non-cationic or surface-modied polymers when administering nanoparticles systemically to pre­vent plasma protein adsorption to the nanoparticle surface and RES absorption.

To increase the nanovector systemic retention and circulation time, hydrophilic polymers with neutral charges like polyethylene glycol (PEG) or polyethylene oxide (PEO) are frequently used for surface modication [69]. PEG disguises polymers, reducing hydrophobic interactions with RES. The ether oxygen of PEG forms a hydrogen bond with water molecules, creating a hydrating shell around the nanovec­tor [70]. The nanovector is steric due to the molecular weight and molar ratio of PEG. Recently, PEG conjugates with anticancer drugs were evaluated [71]. To transport paclitaxel, PEO altered a Poly(3-caprolactone) (PCL) nanovector. Also used for sur­face modication include polyvinyl alcohol, polyacryl amide, polyvinyl pyrrolidone, polysorbate-80, and block copolymers such as poloxamer (Pluronic) and poloxamine (Tect ronic) [61].

delivery in KB cells overexpressing folate receptors [80]. By targeted receptor­mediated endocytosis, paclitaxel-loaded PLGA nanoparticles conjugated to wheat germ agglutinin (WGA) demonstrated enhanced anti-proliferation effect in A549 and H1299 cells in another study [81]. Cystatin inhibits the cysteine proteases cathep­sins B and L linked to tumors when enclosed in PLGA nanovectors. MCF-10A neoT cells were destroyed by cytostatin-loaded PLGA nanovectors 160 times faster than by the free drug [61]. Doxorubicin was delivered via PLGA nanovectors by chemical conjugation via an ester link to PLGA polymer, and it showed sustained drug release over a month, improved drug uptake in the HepG2 cell line, and a marginally lower IC50 than free doxorubicin [82].

When internalized, the pH-sensitive PBAE nanovectors release their contents in the acidic tumor microenvironment and the endosomes and lysosomes of cells, making them ideal for the delivery of anticancer drugs. Paclitaxel-loaded PEO­PBAE nanovectors were studied in MDAMB231 human breast cancer cells [83,84]. The surface of a triblock copolymer (PEO/PPO/PEO) was modied to extend the half-life of nanovectors from 10 to 21hours. Within ve hours, it boosted the drug concentration in solid tumors by 5.2 to 23 times. Pluronics, which are polymeric micelles made of ethylene and propylene oxide, can defeat MDR but may also acti­vate complement [85].

The requirement of entirely biodegradable material drives the creation and ongo­ing study of biodegradable llers. Biodegradable llers have been made by combin­ing several natural polymers, such as cellulose, to achieve this goal. The advantages of cellulose nanostructures include the biopolymer’s widespread availability. More­over, cellulose nanostructures may be generated from trash collected from agricul­tural leftovers, a move toward circular economy principles. Bacterial nanocellulose (BNC), cellulose nanobrils (CNFs) or microbrils (CMFs), and cellulose nanocrys­tals (CNCs) are the three types of cellulose nanostructures found according to their origin and structure [86,87]. To produce bacterial nanocellulose, bacteria, namely, Acetobacters, are used. Fibrillar structures called CNFs or CMFs have a diameter of 10–100 nm and a length on the micrometer scale. The diameter of CNF is on the nanometer scale, whereas that of CMF is in the micron range [15]. However, the literature commonly confuses the two concepts. Mechanical delamination of bers at high pressures was the rst source for these materials. Nevertheless, due to the process’s high energy requirements, various options have been developed, such as the use of homogenizers and microuidizers, as well as pretreatments prior to the delam­ination, such as oxidizing or enzymatic treatments [87]. Very crystalline cellulose nanostructures (CNCs) have a single-dimensional size of less than 100 nm and take the form of rods, needles, or whiskers [88]. Acid hydrolysis, in which the cellulose starting material is processed by strong acid conditions, is the most often used way to generate CNC. After that, centrifugation and ltration methods are often used to separate the material into a nal nano product [88].

distributed throughout the polymeric matrix. Once the solvents were removed, the residual material was treated using a twin rotary roller mixer. The addition of the scattered nanoparticles led to a signicant increase in Young’s modulus and ten­sile strength. In addition to the mechanical strengthening, CNC has been shown to increase miscibility between two biodegradable polymer blends, such as PLA and PBS [90].

Green synthetic techniques that prevent the use of harmful solvents and reagents are strongly advised for the production of nanoparticles in line with the current research trend [12,37,95]. In this line, research into the manufacture of metallic par­ticles utilizing plants and extracts is fresh and expanding. In a nutshell, this biogenic technique involves using plant extracts as a reducing agent to help metal ions create nanoparticles later on [38]. This technology has been widely used for biomedical

Au NPs have been effectively employed in biodegradable polymer-based nano­composites to enhance the electrical conductivity, dielectric properties, and ion mobility of the polymer due to the electrical characteristics of noble metal parti­cles [96]. For instance, environmentally friendly nanocomposite materials have been created by employing a variety of plant extracts and green Au NP synthesis. These nanocomposites contain them. To create a lm with a thickness varying from 55 to 100m, different quantities of nanoparticles were added to carboxy methyl cellulose (CMC) solutions. At a temperature of 353 K, a 3-magnitude order increase in elec­trical conductivity was seen compared to pure CMC. Similar to the previous work, another one supports the effectiveness of Au NPs utilized as active llers in PVA­based green nanocomposites [41]. More recently, Au NPs-reinforced biodegradable polymer-based nanocomposites have been developed. Mentha Spicata L. leaf extract was used to create Au NPs. The produced Au NPs were incorporated into a solution with a 70:30 weight ratio of PVA and CMC. Adrop in the dielectric permittivity and increased direct electrical conductivity of 4 magnitude orders were noted [42].