Pharmaceutics

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18 pages, 8963 KiB

Open AccessArticle

Influence of Different Cationic Polymer-Based Micelles on the Corneal Behavior and Anti-Cataract Effect of Diosmetin

by Jing Zhang, Min Zha, Anping Wan, Satya Siva Kishan Yalamarty, Nina Filipczak and Xiang Li

Pharmaceutics 2025, 17(3), 302; https://doi.org/10.3390/pharmaceutics17030302 - 25 Feb 2025

Viewed by 584

Abstract

Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and [...] Read more.

Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)—on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). Methods The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. Results Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a P_app value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. Conclusion The modification of micelle vesicles with different cationic polymers significantly influences their performance in ocular drug delivery. Among the tested formulations, D-M-T stands out due to its multiple advantages, including enhanced transcorneal drug delivery, therapeutic efficacy for DIO, and safety, making it the most promising candidate for ophthalmic applications. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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15 pages, 3230 KiB

Open AccessArticle

Enhanced Ocular Bioavailability and Prolonged Duration via Hydrophilic Surface Nanocomposite Vesicles for Topical Drug Administration

by Sa Huang, Yuan Xu, Yingyao Luo, Zhijiong Wang, Fan Li, Zhenmiao Qin and Junfeng Ban

Pharmaceutics 2024, 16(12), 1496; https://doi.org/10.3390/pharmaceutics16121496 - 21 Nov 2024

Cited by 1 | Viewed by 981

Abstract

Background: Internal ocular diseases, such as macular edema, uveitis, and diabetic macular edema require precise delivery of therapeutic agents to specific regions within the eye. However, the eye’s complex anatomical structure and physiological barriers present significant challenges to drug penetration and distribution. Traditional [...] Read more.

Background: Internal ocular diseases, such as macular edema, uveitis, and diabetic macular edema require precise delivery of therapeutic agents to specific regions within the eye. However, the eye’s complex anatomical structure and physiological barriers present significant challenges to drug penetration and distribution. Traditional eye drops suffer from low bioavailability primarily due to rapid clearance mechanisms. Methods: The novel ocular drug delivery system developed in this study utilizes poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified with cell-penetrating peptides (CPPs). In vitro drug release studies were conducted to evaluate the sustained-release properties of the nanoparticles. Ex vivo experiments using MDCK cells assessed corneal permeability and uptake efficiency. Additionally, in vivo studies were performed in rabbit eyes to determine the nanoparticles’ resistance to elimination by tears and their retention time in the aqueous humor. Results: In vitro drug release studies demonstrated superior sustained-release properties of the nanoparticles. Ex vivo experiments revealed enhanced corneal permeability and increased uptake efficiency by MDCK cells. In vivo studies in rabbit eyes confirmed the nanoparticles’ resistance to elimination by lacrimal fluid and their ability to extend retention time in the aqueous humor. CPP modification significantly improved ocular retention, corneal penetration, and cellular endocytosis efficiency. Conclusions: The CPP-modified PLGA nanoparticles provide an effective and innovative solution for ocular drug delivery, offering improved bioavailability, prolonged retention, and enhanced drug penetration, thereby overcoming the challenges of traditional intraocular drug administration methods. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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19 pages, 3026 KiB

Open AccessArticle

Stable Polymer-Lipid Hybrid Nanoparticles Based on mcl-Polyhydroxyalkanoate and Cationic Liposomes for mRNA Delivery

by Sergey M. Shishlyannikov, Ilya N. Zubkov, Vera V. Vysochinskaya, Nina V. Gavrilova, Olga A. Dobrovolskaya, Ekaterina A. Elpaeva, Mikhail A. Maslov and Andrey Vasin

Pharmaceutics 2024, 16(10), 1305; https://doi.org/10.3390/pharmaceutics16101305 - 7 Oct 2024

Cited by 1 | Viewed by 2015

Abstract

Background/Objectives: The development of polymer–lipid hybrid nanoparticles (PLNs) is a promising area of research, as it can help increase the stability of cationic lipid carriers. Hybrid PLNs are core–shell nanoparticle structures that combine the advantages of both polymer nanoparticles and liposomes, especially in [...] Read more.

Background/Objectives: The development of polymer–lipid hybrid nanoparticles (PLNs) is a promising area of research, as it can help increase the stability of cationic lipid carriers. Hybrid PLNs are core–shell nanoparticle structures that combine the advantages of both polymer nanoparticles and liposomes, especially in terms of their physical stability and biocompatibility. Natural polymers such as polyhydroxyalkanoate (PHA) can be used as a matrix for the PLNs’ preparation. Methods: In this study, we first obtained stable cationic hybrid PLNs using a cationic liposome (CL) composed of a polycationic lipid 2X3 (1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride), helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), and the hydrophobic polymer mcl-PHA, which was produced by the soil bacterium Pseudomonas helmantisensis P1. Results: The new polymer-lipid carriers effectively encapsulated and delivered model mRNA-eGFP (enhanced green fluorescent protein mRNA) to BHK-21 cells. We then evaluated the role of mcl-PHA in increasing the stability of cationic PLNs in ionic solutions using dynamic light scattering data, electrophoretic mobility, and transmission electron microscopy techniques. Conclusions: The results showed that increasing the concentration of PBS (phosphate buffered saline) led to a decrease in the stability of the CLs. At high concentrations of PBS, the CLs aggregate. In contrast, the presence of isotonic PBS did not result in the aggregation of PLNs, and the particles remained stable for 120 h when stored at +4 °C. The obtained results show that PLNs hold promise for further in vivo studies on nucleic acid delivery. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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26 pages, 3627 KiB

Open AccessArticle

Unveiling the Performance of Co-Assembled Hybrid Nanocarriers: Moving towards the Formation of a Multifunctional Lipid/Random Copolymer Nanoplatform

by Efstathia Triantafyllopoulou, Diego Romano Perinelli, Aleksander Forys, Pavlos Pantelis, Vassilis G. Gorgoulis, Nefeli Lagopati, Barbara Trzebicka, Giulia Bonacucina, Georgia Valsami, Natassa Pippa and Stergios Pispas

Pharmaceutics 2024, 16(9), 1204; https://doi.org/10.3390/pharmaceutics16091204 - 13 Sep 2024

Cited by 2 | Viewed by 1369

Abstract

Despite the appealing properties of random copolymers, the use of these biomaterials in association with phospholipids is still limited, as several aspects of their performance have not been investigated. The aim of this work is the formulation of lipid/random copolymer platforms and the [...] Read more.

Despite the appealing properties of random copolymers, the use of these biomaterials in association with phospholipids is still limited, as several aspects of their performance have not been investigated. The aim of this work is the formulation of lipid/random copolymer platforms and the comprehensive study of their features by multiple advanced characterization techniques. Both biomaterials are amphiphilic, including two phospholipids (1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)) and a statistical copolymer of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(diisopropylamino) ethyl methacrylate (DIPAEMA). We examined the design parameters, including the lipid composition, the % comonomer ratio, and the lipid-to-polymer ratio that could be critical for their behavior. The structures were also probed in different conditions. To the best of the authors’ knowledge, this is the first time that P(OEGMA-co-DIPAEMA)/lipid hybrid colloidal dispersions have been investigated from a membrane mechanics, biophysical, and morphological perspective. Among other parameters, the copolymer architecture and the hydrophilic to hydrophobic balance are deemed fundamental parameters for the biomaterial co-assembly, having an impact on the membrane’s fluidity, morphology, and thermodynamics. Exploiting their unique characteristics, the most promising candidates were utilized for methotrexate (MTX) loading to explore their encapsulation capability and potential antitumor efficacy in vitro in various cell lines. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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18 pages, 4995 KiB

Open AccessArticle

Curcumin-Loaded RH60/F127 Mixed Micelles: Characterization, Biopharmaceutical Characters and Anti-Inflammatory Modulation of Airway Inflammation

by Xinli Wang, Yanyan Wang, Tao Tang, Guowei Zhao, Wei Dong, Qiuxiang Li and Xinli Liang

Pharmaceutics 2023, 15(12), 2710; https://doi.org/10.3390/pharmaceutics15122710 - 30 Nov 2023

Cited by 3 | Viewed by 1465

Abstract

Curcumin’s ability to impact chronic inflammatory conditions, such as metabolic syndrome and arthritis, has been widely researched; however, its poor bioavailability limits its clinical application. The present study is focused on the development of curcumin-loaded polymeric nanomicelles as a drug delivery system with [...] Read more.

Curcumin’s ability to impact chronic inflammatory conditions, such as metabolic syndrome and arthritis, has been widely researched; however, its poor bioavailability limits its clinical application. The present study is focused on the development of curcumin-loaded polymeric nanomicelles as a drug delivery system with anti-inflammatory effects. Curcumin was loaded in PEG-60 hydrogenated castor oil and puronic F127 mixed nanomicelles (Cur-RH60/F127-MMs). Cur-RH60/F127-MMs was prepared using the thin film dispersion method. The morphology and releasing characteristics of nanomicelles were evaluated. The uptake and permeability of Cur-RH60/F127-MMs were investigated using RAW264.7 and Caco-2 cells, and their bioavailability and in vivo/vitro anti-inflammatory activity were also evaluated. The results showed that Cur-RH60/F127-MMs have regular sphericity, possess an average diameter smaller than 20 nm, and high encapsulation efficiency for curcumin (89.43%). Cur-RH60/F127-MMs significantly increased the cumulative release of curcumin in vitro and uptake by cells (p < 0.01). The oral bioavailability of Cur-RH60/F127-MMs was much higher than that of curcumin-active pharmaceutical ingredients (Cur-API) (about 9.24-fold). The treatment of cell lines with Cur-RH60/F127-MMs exerted a significantly stronger anti-inflammatory effect compared to Cur-API. In addition, Cur-RH60/F127-MMs significantly reduced OVA-induced airway hyperresponsiveness and inflammation in an in vivo experimental asthma model. In conclusion, this study reveals the possibility of formulating a new drug delivery system for curcumin, in particular nanosized micellar aqueous dispersion, which could be considered a perspective platform for the application of curcumin in inflammatory diseases of the airways. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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Review

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23 pages, 6399 KiB

Open AccessReview

Smart Responsive and Controlled-Release Hydrogels for Chronic Wound Treatment

by Xintao Jia, Zixuan Dou, Ying Zhang, Fanqin Li, Bin Xing, Zheming Hu, Xin Li, Zhongyan Liu, Wenzhuo Yang and Zhidong Liu

Pharmaceutics 2023, 15(12), 2735; https://doi.org/10.3390/pharmaceutics15122735 - 6 Dec 2023

Cited by 17 | Viewed by 3564

Abstract

Chronic wounds are a major health challenge that require new treatment strategies. Hydrogels are promising drug delivery systems for chronic wound healing because of their biocompatibility, hydration, and flexibility. However, conventional hydrogels cannot adapt to the dynamic and complex wound environment, which involves [...] Read more.

Chronic wounds are a major health challenge that require new treatment strategies. Hydrogels are promising drug delivery systems for chronic wound healing because of their biocompatibility, hydration, and flexibility. However, conventional hydrogels cannot adapt to the dynamic and complex wound environment, which involves low pH, high levels of reactive oxygen species, and specific enzyme expression. Therefore, smart responsive hydrogels that can sense and respond to these stimuli are needed. Crucially, smart responsive hydrogels can modulate drug release and eliminate pathological factors by changing their properties or structures in response to internal or external stimuli, such as pH, enzymes, light, and electricity. These stimuli can also be used to trigger antibacterial responses, angiogenesis, and cell proliferation to enhance wound healing. In this review, we introduce the synthesis and principles of smart responsive hydrogels, describe their design and applications for chronic wound healing, and discuss their future development directions. We hope that this review will inspire the development of smart responsive hydrogels for chronic wound healing. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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20 pages, 1774 KiB

Open AccessReview

Hyaluronic Acid Nanogels: A Promising Platform for Therapeutic and Theranostic Applications

by Su Sundee Myint, Chavee Laomeephol, Sirikool Thamnium, Supakarn Chamni and Jittima Amie Luckanagul

Pharmaceutics 2023, 15(12), 2671; https://doi.org/10.3390/pharmaceutics15122671 - 25 Nov 2023

Cited by 13 | Viewed by 4947

Abstract

Hyaluronic acid (HA) nanogels are a versatile class of nanomaterials with specific properties, such as biocompatibility, hygroscopicity, and biodegradability. HA nanogels exhibit excellent colloidal stability and high encapsulation capacity, making them promising tools for a wide range of biomedical applications. HA nanogels can [...] Read more.

Hyaluronic acid (HA) nanogels are a versatile class of nanomaterials with specific properties, such as biocompatibility, hygroscopicity, and biodegradability. HA nanogels exhibit excellent colloidal stability and high encapsulation capacity, making them promising tools for a wide range of biomedical applications. HA nanogels can be fabricated using various methods, including polyelectrolyte complexation, self-assembly, and chemical crosslinking. The fabrication parameters can be tailored to control the physicochemical properties of HA nanogels, such as size, shape, surface charge, and porosity, enabling the rational design of HA nanogels for specific applications. Stimulus-responsive nanogels are a type of HA nanogels that can respond to external stimuli, such as pH, temperature, enzyme, and redox potential. This property allows the controlled release of encapsulated therapeutic agents in response to specific physiological conditions. HA nanogels can be engineered to encapsulate a variety of therapeutic agents, such as conventional drugs, genes, and proteins. They can then be delivered to target tissues with high efficiency. HA nanogels are still under development, but they have the potential to become powerful tools for a wide range of theranostic or solely therapeutic applications, including anticancer therapy, gene therapy, drug delivery, and bioimaging. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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85 pages, 8256 KiB

Open AccessReview

Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery

by Mariia Stepanova, Alexey Nikiforov, Tatiana Tennikova and Evgenia Korzhikova-Vlakh

Pharmaceutics 2023, 15(11), 2641; https://doi.org/10.3390/pharmaceutics15112641 - 20 Nov 2023

Cited by 13 | Viewed by 3899

Abstract

Synthetic polypeptides are biocompatible and biodegradable macromolecules whose composition and architecture can vary over a wide range. Their unique ability to form secondary structures, as well as different pathways of modification and biofunctionalization due to the diversity of amino acids, provide variation in [...] Read more.

Synthetic polypeptides are biocompatible and biodegradable macromolecules whose composition and architecture can vary over a wide range. Their unique ability to form secondary structures, as well as different pathways of modification and biofunctionalization due to the diversity of amino acids, provide variation in the physicochemical and biological properties of polypeptide-containing materials. In this review article, we summarize the advances in the synthesis of polypeptides and their copolymers and the application of these systems for drug delivery in the form of (nano)particles or hydrogels. The issues, such as the diversity of polypeptide-containing (nano)particle types, the methods for their preparation and drug loading, as well as the influence of physicochemical characteristics on stability, degradability, cellular uptake, cytotoxicity, hemolysis, and immunogenicity of polypeptide-containing nanoparticles and their drug formulations, are comprehensively discussed. Finally, recent advances in the development of certain drug nanoformulations for peptides, proteins, gene delivery, cancer therapy, and antimicrobial and anti-inflammatory systems are summarized. Full article

(This article belongs to the Special Issue Polymer-Based Delivery System)

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