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13 pages, 2215 KiB

Open AccessArticle

Synthesis and Characterization of Antibiotic–Loaded Biodegradable Citrate Functionalized Mesoporous Hydroxyapatite Nanocarriers as an Alternative Treatment for Bone Infections

by Nasser H. Alotaibi, Muhammad Usman Munir, Nabil K. Alruwaili, Khalid Saad Alharbi, Ayesha Ihsan, Alanood S. Almurshedi, Ikram Ullah Khan, Syed Nasir Abbas Bukhari, Mubashar Rehman and Naveed Ahmad

Pharmaceutics 2022, 14(5), 975; https://doi.org/10.3390/pharmaceutics14050975 - 30 Apr 2022

Cited by 7 | Viewed by 1762

Abstract

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to [...] Read more.

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to provide an alternative to currently available bone-infection treatments. Here we designed mesoporous hydroxyapatite nanocarriers functionalized with citrate (Ctr–mpHANCs). Amoxicillin (AMX) is used as a model drug to load in Ctr–mpHANCs, and the drug loading was more than 90% due to the porous nature of nanocarriers. Scanning electron microscopy shows the roughly spherical morphology of nanocarriers, and the DLS study showed the approximate size of 92 nm. The Brunauer–Emmett–Teller (BET) specific surface area and pore diameter was found to be about 182.35 m²/g and 4.2 nm, respectively. We noticed that almost 100% of the drug is released from the AMX loaded Ctr–mpHANCs (AMX@Ctr–mpHANCs) in a pH-dependent manner within 3 d and 5 d at pH 2.0 and 4.5, respectively. The sustained drug release behaviour was observed for 15 d at pH 7.4 and no RBCs hemolysis by AMX@Ctr–mpHANCs. The broth dilution and colony forming unit (CFU) assays were used to determine the antimicrobial potential of AMX@Ctr–mpHANCs. It was observed in both studies that AMX@Ctr–mpHANCs showed a significant reduction in the bacterial growth of S. aureus, E. coli, and P. aeruginosa as compared to Ctr–mpHANCs with no bacteria-killing. Thus, we proposed that Ctr–mpHANCs can be used as a drug carrier and a treatment option for bone infections caused by bacteria. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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15 pages, 3034 KiB

Open AccessArticle

Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities

by Ananda Chowdhury, Alexander Marin, David J. Weber and Alexander K. Andrianov

Pharmaceutics 2021, 13(11), 1834; https://doi.org/10.3390/pharmaceutics13111834 - 02 Nov 2021

Cited by 2 | Viewed by 1671

Abstract

Self-assembly of ionically charged small molecule drugs with water-soluble biodegradable polyelectrolytes into nano-scale complexes can potentially offer a novel and attractive approach to improving drug solubility and prolonging its half-life. Nanoassemblies of quisinostat with water-soluble PEGylated anionic polyphosphazene were prepared by gradient-driven escape [...] Read more.

Self-assembly of ionically charged small molecule drugs with water-soluble biodegradable polyelectrolytes into nano-scale complexes can potentially offer a novel and attractive approach to improving drug solubility and prolonging its half-life. Nanoassemblies of quisinostat with water-soluble PEGylated anionic polyphosphazene were prepared by gradient-driven escape of solvent resulting in the reduction of solvent quality for a small molecule drug. A study of binding, analysis of composition, stability, and release profiles was conducted using asymmetric flow field flow fractionation (AF4) and dynamic light scattering (DLS) spectroscopy. Potency assays were performed with WM115 human melanoma and A549 human lung cancer cell lines. The resulting nano-complexes contained up to 100 drug molecules per macromolecular chain and displayed excellent water-solubility and improved hemocompatibility when compared to co-solvent-based drug formulations. Quisinostat release time (complex dissociation) at near physiological conditions in vitro varied from 5 to 14 days depending on initial drug loading. Multimeric complexes displayed dose-dependent potency in cell-based assays and the results were analyzed as a function of complex concentration, as well as total content of drug in the system. The proposed self-assembly process may present a simple alternative to more sophisticated delivery modalities, namely chemically conjugated prodrug systems and nanoencapsulation-based formulations. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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22 pages, 4265 KiB

Open AccessArticle

Designing Multifunctional Devices for Regenerative Pharmacology Based on 3D Scaffolds, Drug-Loaded Nanoparticles, and Thermosensitive Hydrogels: A Proof-of-Concept Study

by Francesco Colucci, Vanessa Mancini, Clara Mattu and Monica Boffito

Pharmaceutics 2021, 13(4), 464; https://doi.org/10.3390/pharmaceutics13040464 - 30 Mar 2021

Cited by 9 | Viewed by 2075

Abstract

Regenerative pharmacology combines tissue engineering/regenerative medicine (TERM) with drug delivery with the aim to improve the outcomes of traditional TERM approaches. In this work, we aimed to design a multicomponent TERM platform comprising a three-dimensional scaffold, a thermosensitive hydrogel, and drug-loaded nanoparticles. We [...] Read more.

Regenerative pharmacology combines tissue engineering/regenerative medicine (TERM) with drug delivery with the aim to improve the outcomes of traditional TERM approaches. In this work, we aimed to design a multicomponent TERM platform comprising a three-dimensional scaffold, a thermosensitive hydrogel, and drug-loaded nanoparticles. We used a thermally induced phase separation method to obtain scaffolds with anisotropic mechanical properties, suitable for soft tissue engineering. A thermosensitive hydrogel was developed using a Poloxamer^® 407-based poly(urethane) to embed curcumin-loaded nanoparticles, obtained by the single emulsion nanoprecipitation method. We found that encapsulated curcumin could retain its antioxidant activity and that embedding nanoparticles within the hydrogel did not affect the hydrogel gelation kinetics nor the possibility to progressively release the drug. The porous scaffold was easily loaded with the hydrogel, resulting in significantly enhanced (4-fold higher) absorption of a model molecule of nutrients (fluorescein isothiocyanate dextran 4kDa) from the surrounding environment compared to pristine scaffold. The developed platform could thus represent a valuable alternative in the treatment of many pathologies affecting soft tissues, by concurrently exploiting the therapeutic effects of drugs, with the 3D framework acting as a physical support for tissue regeneration and the cell-friendly environment represented by the hydrogel. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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14 pages, 5243 KiB

Open AccessArticle

Optimising PLGA-PEG Nanoparticle Size and Distribution for Enhanced Drug Targeting to the Inflamed Intestinal Barrier

by Lauren J. Mohan, Lauren McDonald, Jacqueline S. Daly and Zebunnissa Ramtoola

Pharmaceutics 2020, 12(11), 1114; https://doi.org/10.3390/pharmaceutics12111114 - 19 Nov 2020

Cited by 11 | Viewed by 2977

Abstract

Oral nanomedicines are being investigated as an innovative strategy for targeted drug delivery to treat inflammatory bowel diseases. Preclinical studies have shown that nanoparticles (NPs) can preferentially penetrate inflamed intestinal tissues, allowing for targeted drug delivery. NP size is a critical factor affecting [...] Read more.

Oral nanomedicines are being investigated as an innovative strategy for targeted drug delivery to treat inflammatory bowel diseases. Preclinical studies have shown that nanoparticles (NPs) can preferentially penetrate inflamed intestinal tissues, allowing for targeted drug delivery. NP size is a critical factor affecting their interaction with the inflamed intestinal barrier and this remains poorly defined. In this study we aimed to assess the impact of NP particle size (PS) and polydispersity (PDI) on cell interaction and uptake in an inflamed epithelial cell model. Using 10, 55 and 100 mg/mL poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG), NPs of 131, 312 and 630 nm PS, respectively, were formulated by solvent dispersion. NP recovery was optimised by differential centrifugation to yield NPs of decreased and unimodal size distribution. NP-cell interaction was assessed in healthy and inflamed caco-2 cell monolayers. Results show that NP interaction with caco-2 cells increased with increasing PS and PDI and was significantly enhanced in inflamed cells. Trypan blue quenching revealed that a significant proportion of multimodal NPs were primarily membrane bound, while monomodal NPs were internalized within cells. These results are interesting as the PS and PDI of NPs can be optimised to allow targeting of therapeutic agents to the epithelial membrane and/or intracellular targets in the inflamed intestinal epithelium. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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15 pages, 3061 KiB

Open AccessArticle

Development of ErbB2-Targeting Liposomes for Enhancing Drug Delivery to ErbB2-Positive Breast Cancer

by Sho Ueno, Min Woo Kim, Gibok Lee, Yong Il Park, Takuro Niidome and Ruda Lee

Pharmaceutics 2020, 12(6), 585; https://doi.org/10.3390/pharmaceutics12060585 - 24 Jun 2020

Cited by 4 | Viewed by 3242

Abstract

ErbB2 is a type of receptor tyrosine kinase, which is known to be involved in tumorigenesis, tumor aggressiveness, and clinical outcome. ErbB2-targeting therapy using therapeutic antibodies has been successful in breast cancer treatment. However, the need for repeated treatments and the high cost [...] Read more.

ErbB2 is a type of receptor tyrosine kinase, which is known to be involved in tumorigenesis, tumor aggressiveness, and clinical outcome. ErbB2-targeting therapy using therapeutic antibodies has been successful in breast cancer treatment. However, the need for repeated treatments and the high cost are major disadvantages with monoclonal antibody therapies. Compared with antibodies, peptides are cheap, relatively stable, and have low immunogenicity. We have developed a highly specific cancer-targeting drug delivery system using a targeting peptide to maximize the therapeutic efficiency of rapamycin and to help prevent drug resistance in ErbB2-positive breast cancer. Physicochemical characterization confirmed the successful construction of ErbB2-targeting liposomes (^ErbB2Lipo). A comparison of a scrambled peptide (ScrErbB2) with the ErbB2-targeting peptide confirmed that these peptides had similar properties except for the targeting ability. The ^ErbB2Lipo exhibited higher delivery efficiency in ErbB2 positive BT-474 cells than non-targeting liposomes conjugated with ScrErbB2 (^ScrErbB2Lipo). This peptide-targeting strategy has the potential to improve the efficacy of chemotherapy in ErbB2-positive cancers. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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Review

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32 pages, 2545 KiB

Open AccessReview

Nanomedicine for Gene Delivery and Drug Repurposing in the Treatment of Muscular Dystrophies

by Ilaria Andreana, Mathieu Repellin, Flavia Carton, David Kryza, Stéphanie Briançon, Bénédicte Chazaud, Rémi Mounier, Silvia Arpicco, Manuela Malatesta, Barbara Stella and Giovanna Lollo

Pharmaceutics 2021, 13(2), 278; https://doi.org/10.3390/pharmaceutics13020278 - 19 Feb 2021

Cited by 16 | Viewed by 5267

Abstract

Muscular Dystrophies (MDs) are a group of rare inherited genetic muscular pathologies encompassing a variety of clinical phenotypes, gene mutations and mechanisms of disease. MDs undergo progressive skeletal muscle degeneration causing severe health problems that lead to poor life quality, disability and premature [...] Read more.

Muscular Dystrophies (MDs) are a group of rare inherited genetic muscular pathologies encompassing a variety of clinical phenotypes, gene mutations and mechanisms of disease. MDs undergo progressive skeletal muscle degeneration causing severe health problems that lead to poor life quality, disability and premature death. There are no available therapies to counteract the causes of these diseases and conventional treatments are administered only to mitigate symptoms. Recent understanding on the pathogenetic mechanisms allowed the development of novel therapeutic strategies based on gene therapy, genome editing CRISPR/Cas9 and drug repurposing approaches. Despite the therapeutic potential of these treatments, once the actives are administered, their instability, susceptibility to degradation and toxicity limit their applications. In this frame, the design of delivery strategies based on nanomedicines holds great promise for MD treatments. This review focuses on nanomedicine approaches able to encapsulate therapeutic agents such as small chemical molecules and oligonucleotides to target the most common MDs such as Duchenne Muscular Dystrophy and the Myotonic Dystrophies. The challenge related to in vitro and in vivo testing of nanosystems in appropriate animal models is also addressed. Finally, the most promising nanomedicine-based strategies are highlighted and a critical view in future developments of nanomedicine for neuromuscular diseases is provided. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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26 pages, 3656 KiB

Open AccessReview

Biodegradable Nanoparticle for Cornea Drug Delivery: Focus Review

by Mohammadmahdi Mobaraki, Madjid Soltani, Samaneh Zare Harofte, Elham L. Zoudani, Roshanak Daliri, Mohamadreza Aghamirsalim and Kaamran Raahemifar

Pharmaceutics 2020, 12(12), 1232; https://doi.org/10.3390/pharmaceutics12121232 - 18 Dec 2020

Cited by 27 | Viewed by 4160

Abstract

During recent decades, researchers all around the world have focused on the characteristic pros and cons of the different drug delivery systems for cornea tissue change for sense organs. The delivery of various drugs for cornea tissue is one of the most attractive [...] Read more.

During recent decades, researchers all around the world have focused on the characteristic pros and cons of the different drug delivery systems for cornea tissue change for sense organs. The delivery of various drugs for cornea tissue is one of the most attractive and challenging activities for researchers in biomaterials, pharmacology, and ophthalmology. This method is so important for cornea wound healing because of the controllable release rate and enhancement in drug bioavailability. It should be noted that the delivery of various kinds of drugs into the different parts of the eye, especially the cornea, is so difficult because of the unique anatomy and various barriers in the eye. Nanoparticles are investigated to improve drug delivery systems for corneal disease. Biodegradable nanocarriers for repeated corneal drug delivery is one of the most attractive and challenging methods for corneal drug delivery because they have shown acceptable ability for this purpose. On the other hand, by using these kinds of nanoparticles, a drug could reside in various part of the cornea for longer. In this review, we summarized all approaches for corneal drug delivery with emphasis on the biodegradable nanoparticles, such as liposomes, dendrimers, polymeric nanoparticles, niosomes, microemulsions, nanosuspensions, and hydrogels. Moreover, we discuss the anatomy of the cornea at first and gene therapy at the end. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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15 pages, 2313 KiB

Open AccessReview

Recent Development to Explore the Use of Biodegradable Periodic Mesoporous Organosilica (BPMO) Nanomaterials for Cancer Therapy

by Shanmugavel Chinnathambi and Fuyuhiko Tamanoi

Pharmaceutics 2020, 12(9), 890; https://doi.org/10.3390/pharmaceutics12090890 - 18 Sep 2020

Cited by 17 | Viewed by 4072

Abstract

Porous nanomaterials can be used to load various anti-cancer drugs efficiently and deliver them to a particular location in the body with minimal toxicity. Biodegradable periodic mesoporous organosilica nanoparticles (BPMOs) have recently emerged as promising candidates for disease targeting and drug delivery. They [...] Read more.

Porous nanomaterials can be used to load various anti-cancer drugs efficiently and deliver them to a particular location in the body with minimal toxicity. Biodegradable periodic mesoporous organosilica nanoparticles (BPMOs) have recently emerged as promising candidates for disease targeting and drug delivery. They have a large functional surface and well-defined pores with a biodegradable organic group framework. Multiple biodegradation methods have been explored, such as the use of redox, pH, enzymatic activity, and light. Various drug delivery systems using BPMO have been developed. This review describes recent advances in the biomedical application of BPMOs. Full article

(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)

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