International Journal of Molecular Sciences

Research

Jump to: Review

14 pages, 3498 KiB

Open AccessArticle

Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking

by Tamara Melnik, Senda Ben Ameur, Nasreddine Kanfar, Laurent Vinet, Florence Delie and Olivier Jordan

Int. J. Mol. Sci. 2022, 23(10), 5706; https://doi.org/10.3390/ijms23105706 - 20 May 2022

Cited by 10 | Viewed by 3702

Abstract

Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system [...] Read more.

Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challenging. We have synthesized HA-Dopamine conjugates (HA-Dop) with several degrees of substitution (DS) and used two crosslinking methods: initiator-free crosslinking by basic pH shift or commonly used crosslinking by a strong oxidizer, sodium periodate. The rheological properties, bioadhesion to vascular tissue, cytocompatibility with fibroblasts have been compared for both methods. Our results suggest that initiator-free crosslinking provides HA-Dop gels with more adequate properties with regards to vascular application than crosslinking by strong oxidizer. We have also established the cytocompatibility of the initiator-free crosslinked HA-Dop gels and the cytotoxicity of dopamine-sodium periodate combinations. Furthermore, we have incorporated a drug with anti-restenotic effect in perivascular application, atorvastatin, into the gel, which showed adequate release profile for intimal hyperplasia prevention. The oxidizer-free formulation with improved bioadhesion holds promise as an efficient and safe drug delivery system for vascular applications. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

22 pages, 3044 KiB

Open AccessArticle

Comparison between Nanoparticle Encapsulation and Surface Loading for Lysosomal Enzyme Replacement Therapy

by Eameema Muntimadugu, Marcelle Silva-Abreu, Guillem Vives, Maximilian Loeck, Vy Pham, Maria del Moral, Melani Solomon and Silvia Muro

Int. J. Mol. Sci. 2022, 23(7), 4034; https://doi.org/10.3390/ijms23074034 - 6 Apr 2022

Cited by 10 | Viewed by 2944

Abstract

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, [...] Read more.

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, and acid sphingomyelinase (ASM), deficient in types A–B Niemann–Pick disease. Initial screening of size, PDI, ζ potential, and loading resulted in the selection of the Lactel II co-polymer vs. Lactel I or Resomer, and Pluronic F68 surfactant vs. PVA or DMAB. Enzyme input and addition of carrier protein were evaluated, rendering NPs having, e.g., 181 nm diameter, 0.15 PDI, −36 mV ζ potential, and 538 HAse molecules encapsulated per NP. Similar NPs were coated with enzyme, which reduced loading (e.g., 292 HAse molecules/NP). NPs were coated with targeting antibodies (> 122 molecules/NP), lyophilized for storage without alterations, and acceptably stable at physiological conditions. NPs were internalized, trafficked to lysosomes, released active enzyme at lysosomal conditions, and targeted both peripheral organs and the brain after i.v. administration in mice. While both formulations enhanced enzyme delivery compared to free enzyme, encapsulating NPs surpassed coated counterparts (18.4- vs. 4.3-fold enhancement in cells and 6.2- vs. 3-fold enhancement in brains), providing guidance for future applications. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Graphical abstract

20 pages, 1809 KiB

Open AccessArticle

Pioglitazone-Loaded PLGA Nanoparticles: Towards the Most Reliable Synthesis Method

by Biagio Todaro, Aldo Moscardini and Stefano Luin

Int. J. Mol. Sci. 2022, 23(5), 2522; https://doi.org/10.3390/ijms23052522 - 25 Feb 2022

Cited by 14 | Viewed by 5517

Abstract

Recent findings have proved the benefits of Pioglitazone (PGZ) against atherosclerosis and type 2 diabetes. Since the systematic and controllable release of this drug is of significant importance, encapsulation of this drug in nanoparticles (NPs) can minimize uncontrolled issues. In this context, drug [...] Read more.

Recent findings have proved the benefits of Pioglitazone (PGZ) against atherosclerosis and type 2 diabetes. Since the systematic and controllable release of this drug is of significant importance, encapsulation of this drug in nanoparticles (NPs) can minimize uncontrolled issues. In this context, drug delivery approaches based on several poly(lactic-co-glycolic acid) (PLGA) nanoparticles have been rising in popularity due to their promising capabilities. However, a fully reliable and reproducible synthetic methodology is still lacking. In this work, we present a rational optimization of the most critical formulation parameters for the production of PGZ-loaded PLGA NPs by the single emulsification-solvent evaporation or nanoprecipitation methods. We examined the influence of several variables (e.g., component concentrations, phases ratio, injection flux rate) on the synthesis of the PGZ-NPs. In addition, a comparison of these synthetic methodologies in terms of nanoparticle size, polydispersity index (PDI), zeta potential (ζ_p), drug loading (DL%), entrapment efficiency (EE%), and stability is offered. According to the higher entrapment efficiency content, enhanced storage time and suitable particle size, the nanoprecipitation approach appears to be the simplest, most rapid and most reliable synthetic pathway for these drug nanocarriers, and we demonstrated a very slow drug release in PBS for the best formulation obtained by this synthesis. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

19 pages, 8600 KiB

Open AccessArticle

Enhanced Anti-Atherosclerotic Efficacy of pH-Responsively Releasable Ganglioside GM3 Delivered by Reconstituted High-Density Lipoprotein

by Tong Rong, Bo Wei, Meiying Ao, Haonan Zhao, Yuanfang Li, Yang Zhang, Ying Qin, Jinhua Zhou, Fenfen Zhou and Yong Chen

Int. J. Mol. Sci. 2021, 22(24), 13624; https://doi.org/10.3390/ijms222413624 - 20 Dec 2021

Cited by 9 | Viewed by 3298

Abstract

Recently, the atheroprotective role of endogenous GM3 and an atherogenesis-inhibiting effect of exogenous GM3 suggested a possibility of exogenous GM3 being recruited as an anti-atherosclerotic drug. This study seeks to endow exogenous GM3 with atherosclerotic targetability via reconstituted high-density lipoprotein (rHDL), an atherosclerotic [...] Read more.

Recently, the atheroprotective role of endogenous GM3 and an atherogenesis-inhibiting effect of exogenous GM3 suggested a possibility of exogenous GM3 being recruited as an anti-atherosclerotic drug. This study seeks to endow exogenous GM3 with atherosclerotic targetability via reconstituted high-density lipoprotein (rHDL), an atherosclerotic targeting drug nanocarrier. Unloaded rHDL, rHDL loaded with exogenous GM3 at a low concentration (GM3_L-rHDL), and rHDL carrying GM3 at a relatively high concentration (GM3_H-rHDL) were prepared and characterized. The inhibitory effect of GM3-rHDL on lipid deposition in macrophages was confirmed, and GM3-rHDL did not affect the survival of red blood cells. In vivo experiments using ApoE^−/− mice fed a high fat diet further confirmed the anti-atherosclerotic efficacy of exogenous GM3 and demonstrated that GM3 packed in HDL nanoparticles (GM3-rHDL) has an enhanced anti-atherosclerotic efficacy and a reduced effective dose of GM3. Then, the macrophage- and atherosclerotic plaque-targeting abilities of GM3-rHD, most likely via the interaction of ApoA-I on GM3-rHDL with its receptors (e.g., SR-B1) on cells, were certified via a microsphere-based method and an aortic fragment-based method, respectively. Moreover, we found that solution acidification enhanced GM3 release from GM3-rHDL nanoparticles, implying the pH-responsive GM3 release when GM3-rHDL enters the acidic atherosclerotic plaques from the neutral blood. The rHDL-mediated atherosclerotic targetability and pH-responsive GM3 release of GM3-rHDL enhanced the anti-atherosclerotic efficacy of exogenous GM3. The development of the GM3-rHDL nanoparticle may help with the application of exogenous GM3 as a clinical drug. Moreover, the data imply that the GM3-rHDL nanoparticle has the potential of being recruited as a drug nanocarrier with atherosclerotic targetability and enhanced anti-atherosclerotic efficacy. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

14 pages, 9308 KiB

Open AccessArticle

Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment

by Krisztina S. Nagy, Krisztina Toth, Eva Pallinger, Angela Takacs, Laszlo Kohidai, Angela Jedlovszky-Hajdu, Domokos Mathe, Noemi Kovacs, Daniel S. Veres, Krisztian Szigeti, Kristof Molnar, Eniko Krisch and Judit E. Puskas

Int. J. Mol. Sci. 2021, 22(19), 10347; https://doi.org/10.3390/ijms221910347 - 26 Sep 2021

Cited by 4 | Viewed by 2676

Abstract

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA₂-dPEG-DOX₂). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme [...] Read more.

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA₂-dPEG-DOX₂). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA₂-dPEG-DOX₂ would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

10 pages, 2059 KiB

Open AccessArticle

The pH-Dependent Controlled Release of Encapsulated Vitamin B₁ from Liposomal Nanocarrier

by Ádám Juhász, Ditta Ungor, Egon Z. Várkonyi, Norbert Varga and Edit Csapó

Int. J. Mol. Sci. 2021, 22(18), 9851; https://doi.org/10.3390/ijms22189851 - 12 Sep 2021

Cited by 12 | Viewed by 2932

Abstract

In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B₁)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the [...] Read more.

In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B₁)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the sonication and magnetic stirring times used for size regulation, the effect of the concentrations of both asolectin carrier and initial vitamin B₁ on the entrapment efficiency (EE %) was also investigated. Thermoanalytical measurements clearly demonstrated that after the successful encapsulation, only weak interactions were discovered between the carriers and the drug molecules. Moreover, the dissolution profiles under physiological (pH = 7.40) and gastric conditions (pH = 1.50) were also registered and the release profiles of our liposomal B₁ system were compared with the dissolution profile of the pure drug solution and a manufactured tablet containing thiamin hydrochloride as active ingredient. The release curves were evaluated by nonlinear fitting of six different kinetic models. The best goodness of fit, where the correlation coefficients in the case of all three systems were larger than 0.98, was reached by application of the well-known second-order kinetic model. Based on the evaluation, it was estimated that our liposomal nanocarrier system shows 4.5-fold and 1.5-fold larger drug retention compared to the unpackaged vitamin B₁ under physiological conditions and in artificial gastric juice, respectively. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

15 pages, 9288 KiB

Open AccessArticle

Mesoporous Aerogel Microparticles Injected into the Abdominal Cavity of Mice Accumulate in Parathymic Lymph Nodes

by Gábor Király, John Chinonso Egu, Zoltán Hargitai, Ilona Kovács, István Fábián, József Kalmár and Gábor Szemán-Nagy

Int. J. Mol. Sci. 2021, 22(18), 9756; https://doi.org/10.3390/ijms22189756 - 9 Sep 2021

Cited by 6 | Viewed by 3505

Abstract

Mesoporous aerogel microparticles are promising drug delivery systems. However, their in vivo biodistribution pathways and health effects are unknown. Suspensions of fluorescein-labeled silica–gelatin hybrid aerogel microparticles were injected into the peritoneum (abdominal cavity) of healthy mice in concentrations of 52 and 104 mg [...] Read more.

Mesoporous aerogel microparticles are promising drug delivery systems. However, their in vivo biodistribution pathways and health effects are unknown. Suspensions of fluorescein-labeled silica–gelatin hybrid aerogel microparticles were injected into the peritoneum (abdominal cavity) of healthy mice in concentrations of 52 and 104 mg kg⁻¹ in a 3-week-long acute toxicity experiment. No physiological dysfunctions were detected, and all mice were healthy. An autopsy revealed that the aerogel microparticles were not present at the site of injection in the abdominal cavity at the end of the experiment. The histological study of the liver, spleen, kidneys, thymus and lymphatic tissues showed no signs of toxicity. The localization of the aerogel microparticles in the organs was studied by fluorescence microscopy. Aerogel microparticles were not detected in any of the abdominal organs, but they were clearly visible in the cortical part of the parathymic lymph nodes, where they accumulated. The accumulation of aerogel microparticles in parathymic lymph nodes in combination with their absence in the reticuloendothelial system organs, such as the liver or spleen, suggests that the microparticles entered the lymphatic circulation. This biodistribution pathway could be exploited to design passive targeting drug delivery systems for flooding metastatic pathways of abdominal cancers that spread via the lymphatic circulation. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Graphical abstract

23 pages, 6959 KiB

Open AccessArticle

Formation of Multicolor Nanogels Based on Cationic Polyfluorenes and Poly(methyl vinyl ether-alt-maleic monoethyl ester): Potential Use as pH-Responsive Fluorescent Drug Carriers

by Marta Rubio-Camacho, María José Martínez-Tomé, Amalia Mira, Ricardo Mallavia and Carmen Reyes Mateo

Int. J. Mol. Sci. 2021, 22(17), 9607; https://doi.org/10.3390/ijms22179607 - 4 Sep 2021

Cited by 7 | Viewed by 2300

Abstract

In this study, we employed the copolymer poly(methyl vinyl ether-alt-maleic monoethyl ester) (PMVEMA-Es) and three fluorene-based cationic conjugated polyelectrolytes to develop fluorescent nanoparticles with emission in the blue, green and red spectral regions. The size, Zeta Potential, polydispersity, morphology, time-stability and fluorescent properties [...] Read more.

In this study, we employed the copolymer poly(methyl vinyl ether-alt-maleic monoethyl ester) (PMVEMA-Es) and three fluorene-based cationic conjugated polyelectrolytes to develop fluorescent nanoparticles with emission in the blue, green and red spectral regions. The size, Zeta Potential, polydispersity, morphology, time-stability and fluorescent properties of these nanoparticles were characterized, as well as the nature of the interaction between both PMVEMA-Es and fluorescent polyelectrolytes. Because PMVEMA-Es contains a carboxylic acid group in its structure, the effects of pH and ionic strength on the nanoparticles were also evaluated, finding that the size is responsive to pH and ionic strength, largely swelling at physiological pH and returning to their initial size at acidic pHs. Thus, the developed fluorescent nanoparticles can be categorized as pH-sensitive fluorescent nanogels, since they possess the properties of both pH-responsive hydrogels and nanoparticulate systems. Doxorubicin (DOX) was used as a model drug to show the capacity of the blue-emitting nanogels to hold drugs in acidic media and release them at physiological pH, from changes in the fluorescence properties of both nanoparticles and DOX. In addition, preliminary studies by super-resolution confocal microscopy were performed, regarding their potential use as image probes. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

15 pages, 26189 KiB

Open AccessArticle

Formulation, Characterization and Cytotoxicity Effects of Novel Thymoquinone-PLGA-PF68 Nanoparticles

by Nurul Shahfiza Noor, Noor Haida Mohd Kaus, Myron R. Szewczuk and Shahrul Bariyah Sahul Hamid

Int. J. Mol. Sci. 2021, 22(17), 9420; https://doi.org/10.3390/ijms22179420 - 30 Aug 2021

Cited by 19 | Viewed by 3833

Abstract

Thymoquinone has anti-cancer properties. However, its application for clinical use is limited due to its volatile characteristics. The current study aims to develop a polymeric nanoformulation with PLGA-PEG and Pluronics F68 as encapsulants to conserve thymoquinone’s (TQ) biological activity before reaching the target [...] Read more.

Thymoquinone has anti-cancer properties. However, its application for clinical use is limited due to its volatile characteristics. The current study aims to develop a polymeric nanoformulation with PLGA-PEG and Pluronics F68 as encapsulants to conserve thymoquinone’s (TQ) biological activity before reaching the target sites. Synthesis of nanoparticles was successfully completed by encapsulating TQ with polymeric poly (D, L-lactide-co-glycolide)-block-poly (ethylene glycol) and Pluronics F68 (TQ-PLGA-PF68) using an emulsion–solvent evaporation technique. The size and encapsulation efficiency of TQ-PLGA-PF68 nanoparticles were 76.92 ± 27.38 nm and 94%, respectively. TQ released from these encapsulants showed a biphasic released pattern. Cytotoxicity activity showed that tamoxifen-resistant (TamR) MCF-7 breast cancer cells required a higher concentration of TQ-PLGA-PF68 nanoparticles than the parental MCF-7 cells to achieve IC₅₀ (p < 0.05). The other two resistant subtypes (TamR UACC732 inflammatory breast carcinoma and paclitaxel-resistant (PacR) MDA-MB 231 triple-negative breast cell line) required a lower concentration of TQ-PLGA-PF68 nanoparticles compared to their respective parental cell lines (p < 0.05). These findings suggest that TQ encapsulation with PLGA-PEG and Pluronics F68 is a promising anti-cancer agent in mitigating breast cancer resistance to chemotherapeutics. In future studies, the anti-cancer activity of TQ-PLGA-PF68 with the standard chemotherapeutic drugs used for breast cancer treatment is recommended. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

22 pages, 6529 KiB

Open AccessArticle

Physicochemical Characterization and Drug Release Properties of Methyl-Substituted Silica Xerogels Made Using Sol–Gel Process

by Adél Len, Giuseppe Paladini, Loránd Románszki, Ana-Maria Putz, László Almásy, Krisztina László, Szabolcs Bálint, Andraž Krajnc, Manfred Kriechbaum, Andrei Kuncser, József Kalmár and Zoltán Dudás

Int. J. Mol. Sci. 2021, 22(17), 9197; https://doi.org/10.3390/ijms22179197 - 25 Aug 2021

Cited by 10 | Viewed by 3288

Abstract

In this work, a multi-analytical approach involving nitrogen porosimetry, small angle neutron and X-ray scattering, Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, X-ray diffraction, thermal analysis and electron microscopy was applied to organically modified silica-based xerogels obtained through the sol–gel [...] Read more.

In this work, a multi-analytical approach involving nitrogen porosimetry, small angle neutron and X-ray scattering, Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, X-ray diffraction, thermal analysis and electron microscopy was applied to organically modified silica-based xerogels obtained through the sol–gel process. Starting from a tetraethoxysilane (TEOS) precursor, methyltriethoxysilane (MTES) was added to the reaction mixture at two different pH values (2.0 and 4.5) producing hybrid xerogels with different TEOS/MTES molar ratios. Significant differences in the structure were revealed in terms of the chemical composition of the silica network, hydrophilic/hydrophobic profile, particle dimension, pore shape/size and surface characteristics. The combined use of structural characterization methods allowed us to reveal a relation between the cavity dimensions, the synthesis pH value and the grade of methyl substitution. The effect of the structural properties on the controlled Captopril release efficiency has also been tested. This knowledge facilitates tailoring the pore network for specific usage in biological/medical applications. Knowledge on structural aspects, as reported in this work, represents a key starting point for the production of high-performance silica-based hybrid materials showing enhanced efficacy compared to bare silica prepared using only TEOS. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

13 pages, 2679 KiB

Open AccessArticle

Sequential Release of Paclitaxel and Imatinib from Core–Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer

by Zhepeng Liu, Haini Chen, Fengmei Lv, Jun Wang, Shoujin Zhao, Yijun Li, Xuexin Xue, Yu Liu, Gang Wei and Weiyue Lu

Int. J. Mol. Sci. 2021, 22(16), 8760; https://doi.org/10.3390/ijms22168760 - 16 Aug 2021

Cited by 12 | Viewed by 3462

Abstract

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core–shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential [...] Read more.

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core–shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core–shell microparticles were of spherical appearance, with an average size of 14.65 μm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core–shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

16 pages, 3736 KiB

Open AccessArticle

Supramolecular Amphiphiles Based on Pillar[5]arene and Meroterpenoids: Synthesis, Self-Association and Interaction with Floxuridine

by Alan A. Akhmedov, Dmitriy N. Shurpik, Pavel L. Padnya, Alena I. Khadieva, Rustem R. Gamirov, Yulia V. Panina, Asiya F. Gazizova, Denis Yu. Grishaev, Vitaliy V. Plemenkov and Ivan I. Stoikov

Int. J. Mol. Sci. 2021, 22(15), 7950; https://doi.org/10.3390/ijms22157950 - 26 Jul 2021

Cited by 5 | Viewed by 2252

Abstract

In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds are not used in targeted drug delivery systems due to their high affinity for cell membranes, both healthy and in cancer cells. [...] Read more.

In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds are not used in targeted drug delivery systems due to their high affinity for cell membranes, both healthy and in cancer cells. Using the approach of creating supramolecular amphiphiles, we have developed self-assembling systems based on water-soluble pillar[5]arene and synthetic meroterpenoids containing geraniol, myrtenol, farnesol, and phytol fragments. The resulting systems can be used as universal drug delivery systems. It was shown by turbidimetry that the obtained pillar[5]arene/synthetic meroterpenoid systems do not interact with the model cell membrane at pH = 7.4, but the associates are destroyed at pH = 4.1. In this case, the synthetic meroterpenoid is incorporated into the lipid bilayer of the model membrane. The characteristics of supramolecular self-assembly, association constants and stoichiometry of the most stable pillar[5]arene/synthetic meroterpenoid complexes were established by UV-vis spectroscopy and dynamic light scattering (DLS). It was shown that supramolecular amphiphiles based on pillar[5]arene/synthetic meroterpenoid systems form monodisperse associates in a wide range of concentrations. The inclusion of the antitumor drug 5-fluoro-2′-deoxyuridine (floxuridine) into the structure of the supramolecular associate was demonstrated by DLS, 19F, 2D DOSY NMR spectroscopy. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

19 pages, 2853 KiB

Open AccessArticle

Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines

by Elham Jamshidifar, Faten Eshrati Yeganeh, Mona Shayan, Mohammad Tavakkoli Yaraki, Mahsa Bourbour, Ali Moammeri, Iman Akbarzadeh, Hassan Noorbazargan and Nikoo Hossein-Khannazer

Int. J. Mol. Sci. 2021, 22(15), 7948; https://doi.org/10.3390/ijms22157948 - 26 Jul 2021

Cited by 41 | Viewed by 3617

Abstract

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe₂O₄ core was coated by a thin layer of silica, followed by a niosomal structure, allowing us [...] Read more.

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe₂O₄ core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe₂O₄@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe₂O₄@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

11 pages, 3067 KiB

Open AccessArticle

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

by Suji Ryu, Seungyeop Park, Ha Yeon Lee, Hyungjun Lee, Cheong-Weon Cho and Jong-Suep Baek

Int. J. Mol. Sci. 2021, 22(6), 2792; https://doi.org/10.3390/ijms22062792 - 10 Mar 2021

Cited by 28 | Viewed by 5061

Abstract

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including [...] Read more.

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

Review

Jump to: Research

21 pages, 6060 KiB

Open AccessReview

Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy

by Wentao Xia, Zixuan Tao, Bin Zhu, Wenxiang Zhang, Chang Liu, Siyu Chen and Mingming Song

Int. J. Mol. Sci. 2021, 22(17), 9118; https://doi.org/10.3390/ijms22179118 - 24 Aug 2021

Cited by 83 | Viewed by 8042

Abstract

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic [...] Read more.

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

25 pages, 2197 KiB

Open AccessReview

PLGA/PLA-Based Long-Acting Injectable Depot Microspheres in Clinical Use: Production and Characterization Overview for Protein/Peptide Delivery

by Arun Butreddy, Rajendra Prasad Gaddam, Nagavendra Kommineni, Narendar Dudhipala and Chandrashekhar Voshavar

Int. J. Mol. Sci. 2021, 22(16), 8884; https://doi.org/10.3390/ijms22168884 - 18 Aug 2021

Cited by 108 | Viewed by 13820

Abstract

Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are [...] Read more.

Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are encapsulated in the microspheres to increase their bioavailability and provide a long release period (days or months) with constant drug plasma concentration. The biodegradable and biocompatible properties of PLGA/PLA polymers, including but not limited to molecular weight, end group, lactide to glycolide ratio, and minor manufacturing changes, could greatly affect the quality attributes of microsphere formulations such as release profile, size, encapsulation efficiency, and bioactivity of biopharmaceuticals. Besides, the encapsulated proteins/peptides are susceptible to harsh processing conditions associated with microsphere fabrication methods, including exposure to organic solvent, shear stress, and temperature fluctuations. The protein/peptide containing LAI microspheres in clinical use is typically prepared by double emulsion, coacervation, and spray drying techniques. The purpose of this review is to provide an overview of the formulation attributes and conventional manufacturing techniques of LAI microspheres that are currently in clinical use for protein/peptides. Furthermore, the physicochemical characteristics of the microsphere formulations are deliberated. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

19 pages, 3173 KiB

Open AccessReview

Stimuli-Responsive Poly(aspartamide) Derivatives and Their Applications as Drug Carriers

by Guangyan Zhang, Hui Yi and Chenhui Bao

Int. J. Mol. Sci. 2021, 22(16), 8817; https://doi.org/10.3390/ijms22168817 - 16 Aug 2021

Cited by 8 | Viewed by 3530

Abstract

Poly(aspartamide) derivatives, one kind of amino acid-based polymers with excellent biocompatibility and biodegradability, meet the key requirements for application in various areas of biomedicine. Poly(aspartamide) derivatives with stimuli-responsiveness can usually respond to external stimuli to change their chemical or physical properties. Using external [...] Read more.

Poly(aspartamide) derivatives, one kind of amino acid-based polymers with excellent biocompatibility and biodegradability, meet the key requirements for application in various areas of biomedicine. Poly(aspartamide) derivatives with stimuli-responsiveness can usually respond to external stimuli to change their chemical or physical properties. Using external stimuli such as temperature and pH as switches, these smart poly(aspartamide) derivatives can be used for convenient drug loading and controlled release. Here, we review the synthesis strategies for preparing these stimuli-responsive poly(aspartamide) derivatives and the latest developments in their applications as drug carriers. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

20 pages, 1541 KiB

Open AccessReview

Design and Encapsulation of Immunomodulators onto Gold Nanoparticles in Cancer Immunotherapy

by Akshita Chauhan, Tabassum Khan and Abdelwahab Omri

Int. J. Mol. Sci. 2021, 22(15), 8037; https://doi.org/10.3390/ijms22158037 - 27 Jul 2021

Cited by 22 | Viewed by 4285

Abstract

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, [...] Read more.

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shaped geometry, which significantly increases light absorption and provides high photon-to-heat conversion efficiency due to the plasmonic effect. As a result, GNPs are a useful vehicle for delivering antigens and adjuvants that support the immune system in killing tumor cells by facilitating or activating cytotoxic T lymphocytes. This review represents recent progress in encapsulating immunomodulators into GNPs for utility in a cancer immunotherapeutic regimen. Full article

(This article belongs to the Special Issue Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Drug Nanocarriers: Structural Characterisation and Encapsulation Possibilities

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (18 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI