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26 pages, 5480 KiB

Open AccessArticle

Bipolymeric Pectin Millibeads Doped with Functional Polymers as Matrices for the Controlled and Targeted Release of Mesalazine

by Dorota Wójcik-Pastuszka, Aleksandra Potempa and Witold Musiał

Molecules 2020, 25(23), 5711; https://doi.org/10.3390/molecules25235711 - 03 Dec 2020

Cited by 8 | Viewed by 1958

Abstract

Targeted drug delivery systems are a very convenient method of treating inflammatory bowel disease. The properties of pectin make this biopolymer a suitable drug carrier. These properties allow pectin to overcome the diverse environment of the digestive tract and deliver the drug to [...] Read more.

Targeted drug delivery systems are a very convenient method of treating inflammatory bowel disease. The properties of pectin make this biopolymer a suitable drug carrier. These properties allow pectin to overcome the diverse environment of the digestive tract and deliver the drug to the large intestine. This investigation proposed bipolymeric formulations consisting of the natural polymer pectin and a synthetic polymer containing the drug 5-aminosalicylic acid. Pectin beads were prepared via ionotropic gelation involving the interaction between the hydrophilic gel and calcium ions. The obtained formulations consisted of natural polymer, 5-aminosalicylic acid (5-ASA) and one of the synthetic polymers, such as polyacrylic acid, polyvinylpyrrolidone, polyethylene glycol or aristoflex. The release of the drug was carried out employing a basket apparatus (USP 1). The acceptor fluid was pH = 7.4 buffer with added enzyme pectinase to reflect the colon environment. The amount of the released drug was determined using UV-Vis spectrophotometry at a wavelength of λ = 330 nm. The kinetics of the drug dissolution revealed that none of the employed models was appropriate to describe the release process. A kinetic analysis of the release profile during two release stages was carried out. The fastest drug release occurred during the first stage from a formulation containing pectin and polyethylene glycol. However, according to the applied kinetic models, the dissolution of 5-ASA was rather high in the formulation without the synthetic polymer during the second stage. Depending on the formulation, 68–77% of 5-ASA was released in an 8-hour time period. The FTIR and DSC results showed that there was no interaction between the drug and the polymers, but interactions between pectin and synthetic polymers were found. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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13 pages, 2176 KiB

Open AccessArticle

Potential of Naftifine Application for Transungual Delivery

by Indrė Šveikauskaitė and Vitalis Briedis

Molecules 2020, 25(13), 3043; https://doi.org/10.3390/molecules25133043 - 03 Jul 2020

Cited by 6 | Viewed by 2687

Abstract

Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine’s ability to permeate the human nail barrier has not been investigated, thus, the antimycotic potential is not clearly established. This work aims to [...] Read more.

Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine’s ability to permeate the human nail barrier has not been investigated, thus, the antimycotic potential is not clearly established. This work aims to evaluate the effect of penetration enhancing factors on the accumulation of naftifine hydrochloride through human nail clippings. Naftifine polymeric nail lacquers with Eudragit RL100 were developed as a suitable delivery system. Low penetration of naftifine into nail has been determined as less than 10% of applied drug dose accumulated in the nail layers. Incorporation of thioglycolic acid into formulations resulted in increased accumulation of antifungal agent in the nail layers by 100% compared with a control group. Salicylic acid did not effect naftifine accumulation in the human nail. The permeation of naftifine through the nail increased by threefold when the thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO₂ laser. Structural changes of the nail barrier, induced by fractional CO₂ laser, were visualized by microscopy. The results suggest, that naftifine nail penetration could be significantly increased when physical and chemical enhancing factors are applied. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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17 pages, 2917 KiB

Open AccessArticle

Comparative Molecular Transporter Properties of Cyclic Peptides Containing Tryptophan and Arginine Residues Formed through Disulfide Cyclization

by Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari and Keykavous Parang

Molecules 2020, 25(11), 2581; https://doi.org/10.3390/molecules25112581 - 02 Jun 2020

Cited by 3 | Viewed by 3689

Abstract

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated [...] Read more.

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast carcinoma (MDA-MB-231), and normal kidney (LLCPK) cells after 24 and 72 h incubation. Both cyclic [C(WR)₅C] and linear (C(WR)₅C) demonstrated comparable molecular transporter properties versus [WR]₅ in the delivery of a phosphopeptide (F′-GpYEEI) in CCRF-CEM cells. The uptake of F′-GpYEEI in the presence of 1,4-dithiothreitol (DTT) as the reducing agent was significantly improved in case of l(C(WR)₅C), while it was not changed by [C(WR)₅C]. Fluorescence microscopy also demonstrated a significant uptake of F′-GpYEEI in the presence of l(C(WR)₅C). Cyclic [C(WR)₅C] improved the uptake of the fluorescent-labeled anti-HIV drugs F′-d4T, F′-3TC, and F′-FTC by 3.0–4.9-fold. These data indicate that both [C(WR)₅C] and linear (C(WR)₅C) peptides can act as molecular transporters. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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12 pages, 5684 KiB

Open AccessCommunication

Polyvinyl Alcohol/Chitosan/Polyhexamethylene Biguanide Phase Separation System: A Potential Topical Antibacterial Formulation with Enhanced Antimicrobial Effect

by Yunzhou Ni, Zhixiang Qian, Yu Yin, Weien Yuan, Fei Wu and Tuo Jin

Molecules 2020, 25(6), 1334; https://doi.org/10.3390/molecules25061334 - 15 Mar 2020

Cited by 10 | Viewed by 3510

Abstract

An aqueous polyvinyl alcohol (PVA)/chitosan (CHT)/polyhexamethylene biguanide (PHMB) blends (PVA/CHT/PHMB blends) has been developed as a potential low dose topical antibacterial formulation with enhanced antimicrobial effect. The preparation of PVA/CHT/PHMB blends was quite facilely, with just dissolved PVA, CHT, PHMB in water in [...] Read more.

An aqueous polyvinyl alcohol (PVA)/chitosan (CHT)/polyhexamethylene biguanide (PHMB) blends (PVA/CHT/PHMB blends) has been developed as a potential low dose topical antibacterial formulation with enhanced antimicrobial effect. The preparation of PVA/CHT/PHMB blends was quite facilely, with just dissolved PVA, CHT, PHMB in water in order. There was the aggregates with 100 nm size around induced by phase separation in the blends and an aqueous two-phase system (ATPS) formed, as non-ionic polymer PVA formed a continuous phase and cationic polymer CHT and PHMB formed dispersed phases. The minimum inhibitory concentration (MIC) of PHMB in the PVA/CHT/PHMB blends was 0.5μg/mL, which was four times lower than the MIC of PHMB individually. A phase separation increased zeta potential mechanism was proposed to explain the enhanced antibacterial activities. In addition, the blends could easily form film on the skin surface with good water vapor permeability and be used as a liquid bandage to accelerate the scratch wound healing process of nude mouse. These findings provide experimental evidence that the PHMB-functionalized blends could be further explored as low-dose topical antibacterial formulations, and the nano-sized phase separation strategy could be used to design novel low-dose topical antibacterial formulations with an enhanced antimicrobial effect. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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22 pages, 5337 KiB

Open AccessArticle

Sterically Stabilised Polymeric Mesoporous Silica Nanoparticles Improve Doxorubicin Efficiency: Tailored Cancer Therapy

by Thashini Moodley and Moganavelli Singh

Molecules 2020, 25(3), 742; https://doi.org/10.3390/molecules25030742 - 08 Feb 2020

Cited by 27 | Viewed by 4309

Abstract

The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are [...] Read more.

The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are attractive nanocarriers due to their biodegradable, biocompatible, and relative malleable porous frameworks that can be functionalized for enhanced targeting and delivery in a variety of disease models. The optimal formulation of an MSN with polyethylene glycol (2% and 5%) and chitosan was undertaken, to produce sterically stabilized, hydrophilic MSNs, capable of efficient loading and delivery of the hydrophobic anti-neoplastic drug, doxorubicin (DOX). The pH-sensitive release kinetics of DOX, together with the anticancer, apoptosis and cell-cycle activities of DOX-loaded MSNs in selected cancer cell lines were evaluated. MSNs of 36–60 nm in size, with a pore diameter of 9.8 nm, and a cumulative surface area of 710.36 m²/g were produced. The 2% pegylated MSN formulation (PCMSN) had the highest DOX loading capacity (0.98 mg_dox/mg_msn), and a sustained release profile over 72 h. Pegylated-drug nanoconjugates were effective at a concentration range between 20–50 μg/mL, inducing apoptosis in cancer cells, and affirming their potential as effective drug delivery vehicles. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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17 pages, 5891 KiB

Open AccessArticle

Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals

by Jun Wang, Feng-Mei Lv, Dong-Li Wang, Jian-Liang Du, Hai-Yan Guo, Hai-Ni Chen, Shou-Jin Zhao, Zhe-Peng Liu and Yu Liu

Molecules 2020, 25(3), 604; https://doi.org/10.3390/molecules25030604 - 30 Jan 2020

Cited by 23 | Viewed by 3445

Abstract

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time [...] Read more.

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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18 pages, 4390 KiB

Open AccessArticle

Development of Asialoglycoprotein Receptor-Targeted Nanoparticles for Selective Delivery of Gemcitabine to Hepatocellular Carcinoma

by Anroop B. Nair, Jigar Shah, Bandar E. Al-Dhubiab, Snehal S. Patel, Mohamed A. Morsy, Vimal Patel, Vishal Chavda, Shery Jacob, Nagaraja Sreeharsha, Pottathil Shinu, Mahesh Attimarad and Katharigatta N. Venugopala

Molecules 2019, 24(24), 4566; https://doi.org/10.3390/molecules24244566 - 13 Dec 2019

Cited by 48 | Viewed by 4153

Abstract

Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein [...] Read more.

Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein receptors expressed on hepatocytes. Nanoparticles were formulated (G1–G5) by an ionic gelation method and evaluated for various physicochemical characteristics. Targeting efficacy of formulation G4 was evaluated in rats. Physicochemical characteristics exhibited by nanoparticles were optimal for administering and targeting gemcitabine effectively to the liver. The biphasic release behavior observed with G4 can provide higher drug concentration and extend the pharmacotherapy in the liver target site. Rapid plasma clearance of gemcitabine (70% in 30 min) from G4 was noticed in rats with HCC as compared to pure drug (p < 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; p < 0.0001) demonstrated excellent liver targeting by G4, while mitigating systemic toxicity. Morphological, biochemical, and histopathological examination as well as blood levels of the tumor marker, alpha-fetoprotein, in rats confirmed the curative effect of G4. In conclusion, this study demonstrated site-specific delivery and enhanced in vivo anti-HCC efficacy of gemcitabine by G4, which could function as promising carrier in hepatoma. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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Review

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27 pages, 2902 KiB

Open AccessFeature PaperReview

Novel Tamoxifen Nanoformulations for Improving Breast Cancer Treatment: Old Wine in New Bottles

by Candace M. Day, Shane M. Hickey, Yunmei Song, Sally E. Plush and Sanjay Garg

Molecules 2020, 25(5), 1182; https://doi.org/10.3390/molecules25051182 - 05 Mar 2020

Cited by 44 | Viewed by 9305

Abstract

Breast cancer (BC) is one of the leading causes of death from cancer in women; second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite [...] Read more.

Breast cancer (BC) is one of the leading causes of death from cancer in women; second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite having striking efficacy in BC therapy, concerns regarding the dose-dependent carcinogenicity of TAM still persist, restricting its therapeutic applications. Nanotechnology has emerged as one of the most important strategies to solve the issue of TAM toxicity, owing to the ability of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Various TAM-containing-nanosystems have been successfully fabricated to selectively deliver TAM to specific molecular targets found on tumour membranes, reducing unwanted toxic effects. This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC. A detailed discussion of various nanoformulation strategies used to deliver lower doses of TAM selectively to breast tumours will then follow. Finally, a commentary on future perspectives of TAM being employed as a targeting vector, to guide the delivery of other therapeutic and diagnostic agents selectively to breast tumours will be presented. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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