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1.
Oncol Res ; 32(4): 769-784, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560569

RESUMO

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Neoplasias da Mama , Poloxaleno , Humanos , Feminino , Micelas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ligantes , Qualidade de Vida , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Polímeros/química , Polímeros/uso terapêutico , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias Ósseas/tratamento farmacológico , Alendronato/farmacologia , Alendronato/química , Alendronato/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico
2.
ACS Nano ; 18(11): 8392-8410, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38450656

RESUMO

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Nanomedicina , RNA Mensageiro/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Fatores de Crescimento do Endotélio Vascular , Polímeros/uso terapêutico , Pulmão/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico
3.
Medicine (Baltimore) ; 103(11): e37506, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489708

RESUMO

Poly-L-lactin acid (PLLA) has been widely used in the field of bio-medicine. In 2004, as an injectable material, PLLA was approved by the FDA to treat AIDS-related facial atrophy. Since then, several injectable stuffs containing PLLA have been approved for marketing in various countries and regions. Recently, PLLA has often been used to treat facial rejuvenation problems like cutaneous depressions and static wrinkles which always induce unsatisfactory facial expression. This review introduces the physicochemical properties, regeneration stimulating mechanism, applications in aesthetics and injectable comorbidity of PLLA.


Assuntos
Técnicas Cosméticas , Poliésteres , Polímeros , Humanos , Polímeros/uso terapêutico , Rejuvenescimento , Ácido Láctico , Estética , Reprodução
4.
Biomacromolecules ; 25(4): 2302-2311, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38507248

RESUMO

Photodynamic therapy (PDT) employs photosensitizers to convert nearby oxygen into toxic singlet oxygen (1O2) upon laser light irradiation, showing great potential as a noninvasive approach for tumor ablation. However, the therapeutic efficacy of PDT is essentially impeded by π-π stacking and the aggregation of photosensitizers. Herein, we propose a tumor microenvironment-triggered self-adaptive nanoplatform to weaken the aggregation of photosensitizers by selenium-based oxidation at the tumor site. The selenide units in a selenium-based porphyrin-containing amphiphilic copolymer (PSe) could be oxidized into hydrophilic selenoxide units, leading to the nanoplatform self-expansion and stretching of the distance between intramolecular porphyrin units. This process could provide a better switch to greatly reduce the aggregation of photosensitive porphyrin units, generating more 1O2 upon laser irradiation. As verified in a series of in vitro and in vivo studies, PSe could be efficiently self-adapted at tumor sites, thus significantly enhancing the PDT therapeutic effect against solid tumors and minimizing side effects.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Selênio , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral , Selênio/uso terapêutico , Nanopartículas/uso terapêutico , Oxigênio , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Polímeros/uso terapêutico , Porfirinas/farmacologia , Linhagem Celular Tumoral
5.
Int J Biol Macromol ; 264(Pt 2): 130645, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460633

RESUMO

Hyaluronic acid (HA), a biodegradable, biocompatible and non-immunogenic therapeutic polymer is a key component of the cartilage extracellular matrix (ECM) and has been widely used to manage two major types of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA). OA joints are characterized by lower concentrations of depolymerized (low molecular weight) HA, resulting in reduced physiological viscoelasticity, while in RA, the associated immune cells are over-expressed with various cell surface receptors such as CD44. Due to HA's inherent viscoelastic property and its ability to target CD44, there has been a surge of interest in developing HA-based systems to deliver various bioactives (drugs and biologics) and manage arthritis. Considering therapeutic benefits of HA in arthritis management and potential advantages of novel delivery systems, bioactive delivery through HA-based systems is beginning to display improved outcomes over bioactive only treatment. The benefits include enhanced bioactive uptake due to receptor-mediated targeting, prolonged retention of bioactives in the synovium, reduced expressions of proinflammatory mediators, enhanced cartilage regeneration, reduced drug toxicity due to sustained release, and improved and cost-effective treatment. This review provides an underlying rationale to prepare and use HA-based bioactive delivery systems for arthritis applications. With special emphasis given to preclinical/clinical results, this article reviews various bioactive-loaded HA-based particulate carriers (organic and inorganic), gels, scaffolds and polymer-drug conjugates that have been reported to treat and manage OA and RA. Furthermore, the review identifies several key challenges and provides valuable suggestions to address them. Various developments, strategies and suggestions described in this review may guide the formulation scientists to optimize HA-based bioactive delivery systems as an effective approach to manage and treat arthritis effectively.


Assuntos
Artrite Reumatoide , Osteoartrite , Humanos , Ácido Hialurônico/uso terapêutico , Ácido Hialurônico/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Artrite Reumatoide/metabolismo , Preparações Farmacêuticas , Polímeros/uso terapêutico
6.
ACS Macro Lett ; 13(3): 288-295, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38368530

RESUMO

We report a facile stimuli-responsive strategy to generate reactive oxygen and nitrogen species (ROS and RNS) in the biological milieu from a photocleavable water-soluble block copolymer under visible light irradiation (427 nm, 2.25 mW/cm2). An anthraquinone-based water-soluble polymeric nitric oxide (NO) donor (BCPx-NO) is synthesized, which exhibits NO release in the range of 40-65 µM within 10 h of photoirradiation with a half-life of 30-103 min. Additionally, BCPx-NO produces peroxynitrite (ONOO-) and singlet oxygen (1O2) under photoirradiation. To understand the mechanism of NO release and photolysis of the functional group under blue light, we prepared a small-molecule anthraquinone-based N-nitrosamine (NOD). The cellular investigation of the effect of spatiotemporally controlled ONOO- and 1O2 generation from the NO donor polymeric nanoparticles in a triple negative breast adenocarcinoma (MDA-MB-231) under visible light irradiation (white light, 5.83 mW/cm2; total dose 31.5 J/cm2) showed an IC50 of 0.6 mg/mL. The stimuli-responsive strategy using a photolabile water-soluble block copolymer employed to generate ROS and RNS in a biological setting widens the horizon for their potential in cancer therapy.


Assuntos
Neoplasias , Ácido Peroxinitroso , Humanos , Ácido Peroxinitroso/uso terapêutico , Espécies Reativas de Oxigênio/uso terapêutico , Polímeros/uso terapêutico , Espécies Reativas de Nitrogênio/uso terapêutico , Luz , Oxigênio/uso terapêutico , Óxido Nítrico/uso terapêutico , Antraquinonas/uso terapêutico , Neoplasias/tratamento farmacológico
7.
Nat Commun ; 15(1): 1118, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320994

RESUMO

Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.


Assuntos
Glioblastoma , Camundongos , Animais , Glioblastoma/patologia , Micelas , Inibidores de Checkpoint Imunológico/uso terapêutico , Polímeros/uso terapêutico , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/uso terapêutico , Imunoterapia , Microambiente Tumoral
8.
Drugs ; 84(3): 363-368, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38409574

RESUMO

Berdazimer topical gel, 10.3% (ZELSUVMI™) is a nitric oxide (NO) releasing topical gel developed by Novan Inc. (a Ligand Pharmaceuticals company) for the treatment of molluscum contagiosum (MC). Novan has used their proprietary NO-based technology platform (NITRICIL™), which stores gaseous NO species on large polymers, in the development of berdazimer topical gel, 10.3%. In January 2024, berdazimer topical gel, 10.3% was approved for the topical treatment of MC in adult and paediatric patients 1 year of age and older in the USA. This article summarizes the milestones in the development of berdazimer topical gel, 10.3% leading to this first approval for the treatment of MC.


Assuntos
Molusco Contagioso , Adulto , Criança , Humanos , Molusco Contagioso/tratamento farmacológico , Administração Tópica , Géis/uso terapêutico , Polímeros/uso terapêutico
9.
Antiviral Res ; 224: 105835, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401714

RESUMO

Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing. Here we report on an optimized in vivo DHBV duck model and explore several characteristics of NAP treatment. REP2139 was efficacious in reducing DHBV DNA and DHBsAg levels in approximately half of the treated ducks, whether administered intraperitoneally or subcutaneously. Intrahepatic or serum NAP concentrations did not correlate with efficacy, nor did the appearance of anti-DHBsAg antibodies. Furthermore, NAP efficacy was only observed in experimentally infected ducks, not in endogenously infected ducks (vertical transmission). REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy. Destabilized REP2165 showed a different activity profile with a more homogenous antiviral response followed by a faster rebound. In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders.


Assuntos
Infecções por Hepadnaviridae , Vírus da Hepatite B do Pato , Hepatite B Crônica , Hepatite Viral Animal , Ácidos Nucleicos , Animais , Humanos , Vírus da Hepatite B do Pato/genética , Hepatite B Crônica/tratamento farmacológico , Antivirais/farmacologia , Ácidos Nucleicos/uso terapêutico , Polímeros/uso terapêutico , Resultado do Tratamento , Patos/genética , DNA Viral , Hepatite Viral Animal/tratamento farmacológico , Vírus da Hepatite B , Infecções por Hepadnaviridae/tratamento farmacológico , Infecções por Hepadnaviridae/veterinária , Fígado
10.
AAPS PharmSciTech ; 25(3): 47, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424367

RESUMO

Lung cancer is one of the most severe lethal malignancies, with approximately 1.6 million deaths every year. Lung cancer can be broadly categorised into small and non-small-cell lung cancer. The traditional chemotherapy is nonspecific, destroys healthy cells and produces systemic toxicity; targeted inhalation drug delivery in conjunction with nanoformulations has piqued interest as an approach for improving chemotherapeutic drug activity in the treatment of lung cancer. Our aim is to discuss the impact of polymer and lipid-based nanocarriers (polymeric nanoparticles, liposomes, niosomes, nanostructured lipid carriers, etc.) to treat lung cancer via the inhalational route of drug administration. This review also highlights the clinical studies, patent reports and latest investigations related to lung cancer treatment through the pulmonary route. In accordance with the PRISMA guideline, a systematic literature search was carried out for published works between 2005 and 2023. The keywords used were lung cancer, pulmonary delivery, inhalational drug delivery, liposomes in lung cancer, nanotechnology in lung cancer, etc. Several articles were searched, screened, reviewed and included. The analysis demonstrated the potential of polymer and lipid-based nanocarriers to improve the entrapment of drugs, sustained release, enhanced permeability, targeted drug delivery and retention impact in lung tissues. Patents and clinical observations further strengthen the translational potential of these carrier systems for human use in lung cancer. This systematic review demonstrated the potential of pulmonary (inhalational) drug delivery approaches based on nanocarriers for lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Humanos , Lipossomos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Portadores de Fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Pulmão , Polímeros/uso terapêutico , Lipídeos
11.
J Control Release ; 368: 265-274, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423474

RESUMO

Combined photodynamic therapy (PDT) and photothermal therapy (PTT) not only effectively reduce the hypoxic resistance to PDT, but also overcome the heat shock effect to PTT. However, the residual phototherapeutic agents still produce reactive oxygen species (ROS) to damage normal tissue under sunlight after treatment, which induces undesirable side effects to limit their biomedical application. Herein, a facile strategy is proposed to construct a biodegradable semiconducting polymer p-DTT, which is constructed by thieno[3,2-b]thiophene modified diketopyrrolopyrrole and (E)-1,2-bis(5-(trimethylstannyl)thiophen-2-yl)ethene moieties, to avoid the post-treatment side effects of phototherapy. Additionally, p-DTT exhibits strong photoacoustic (PA) for imaging, as well as good ROS production capacity and high photothermal conversion efficiency for synergistic PDT and PTT, which has been confirmed by both in vitro and in vivo results. After phototherapy, p-DTT could be gradually oxidized and degraded by endogenous ClO-, and subsequently lose ROS production and photothermal conversion capacities, which can guarantee the post-treatment safety, and address above key limitation of traditional phototherapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio , Fototerapia , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico
12.
Int J Biol Macromol ; 262(Pt 1): 129434, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232877

RESUMO

The field of cancer therapy is advancing rapidly, placing a crucial emphasis on innovative drug delivery systems. The increasing global impact of cancer highlights the need for creative therapeutic strategies. Natural polymer-based nanotherapeutics have emerged as a captivating avenue in this pursuit, drawing substantial attention due to their inherent attributes. These attributes include biodegradability, biocompatibility, negligible toxicity, extended circulation time, and a wide range of therapeutic payloads. The unique size, shape, and morphological characteristics of these systems facilitate profound tissue penetration, complementing active and passive targeting strategies. Moreover, these nanotherapeutics exploit specific cellular and subcellular trafficking pathways, providing precise control over drug release kinetics. This comprehensive review emphasizes the utilization of naturally occurring polymers such as polysaccharides (e.g., chitosan, hyaluronic acid, alginates, dextran, and cyclodextrin) and protein-based polymers (e.g., ferritin, gelatin, albumin) as the foundation for nanoparticle development. The paper meticulously examines their in vitro characteristics alongside in vivo efficacy, particularly focusing on their pivotal role in ameliorating diverse types of solid tumors within cancer therapy. The amalgamation of material science ingenuity and biological insight has led to the formulation of these nanoparticles, showcasing their potential to reshape the landscape of cancer treatment.


Assuntos
Quitosana , Nanopartículas , Neoplasias , Humanos , Polímeros/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Polissacarídeos/uso terapêutico , Quitosana/uso terapêutico
13.
Nat Commun ; 15(1): 170, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167652

RESUMO

Practical photodynamic therapy calls for high-performance, less O2-dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based photosensitizers exhibit excellent photocatalytic performance, but the in vivo applications are hindered by conventional O2-dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy for engineering iridium complexes exhibiting Type-I photochemistry and enhancing absorption intensity in the blue to near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1, where the iridium atom is covalently coupled to the polymer backbone, is over 80 times higher than that of its mother polymer without iridium under 680 nm irradiation. This strategy also works effectively when the iridium atom is directly included (Ir-P2) in the polymer backbones, exhibiting wide generality. The metallopolymer nanoparticles exhibiting efficient O2•- generation are conjugated with integrin αvß3 binding cRGD to achieve targeted photodynamic therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Irídio/química , Hipóxia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Polímeros/uso terapêutico , Microambiente Tumoral
14.
J Biotechnol ; 381: 100-108, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38181982

RESUMO

Metal sulfide nanoparticles are synthesized for their biomedical applications, including cancer drug targeting. This paper reports a novel nanocomposite made of praseodymium sulfide nanoparticles and poly-cyclodextrin. The praseodymium sulfide nanoparticles were synthesized hydrothermal, autoclaving the nitrate precursors at 150 °C for 18 hours. The material is characterized using XRD and shows an orthorhombic crystal system with high crystallinity. The size and morphology of the nanomaterial were optimized. The material shows a rod-shaped morphology, as seen in the TEM image, with 150 ± 3 nm length and 25 ± 5 nm width. Particle size analysis supports this size range. The colloidal particles were stable in the aqueous medium without precipitation at neutral pH. The elements in the material in the polymer-coated form and their electronic states are studied by X-ray photoelectron spectroscopy. Thermogravimetry confirms that the material contains about 18.5% of the weight of the polymer. The material has an observable magnetic property at room temperature due to the praseodymium element. The UV-vis-NIR absorption spectrum of the material shows a long absorption range that extends to 1200 nm. The drug 5-fluorouracil is encapsulated in the nanoparticles through host: guest association, and its release profile is analyzed. The release is modulated at a slightly acidic pH, indicating the pH-tunability. The nanoparticles and 5-fluorouracil were taken in the w/w ratio of 2:1 (2/1 mg in 1 mL of deionized water). Further, the in vitro anticancer activity of the drug-encapsulated material is screened on breast cancer and non-cancerous cell lines. The IC50 values are reported, and the advantageous properties of the material as drug carriers are discussed.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Praseodímio/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Antineoplásicos/química , Fluoruracila/química , Fluoruracila/uso terapêutico , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Polímeros/uso terapêutico , Nanopartículas/química
15.
ACS Biomater Sci Eng ; 10(3): 1869-1879, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38291563

RESUMO

Localized photodynamic therapy (PDT) uses a polymeric-photosensitizer (PS)-embedded, covered self-expandable metallic stent (SEMS). PDT is minimally invasive and a noteworthy potential alternative for treating esophageal strictures, where surgery is not a viable option. However, preclinical evidence is insufficient, and optimized irradiation energy dose ranges for localized PDT are unclear. Herein, we validated the irradiation energy doses of the SEMS (embedded in a PS using chlorin e6 [Ce6] and covered in silicone) and PDT-induced tissue changes in a rat esophagus. Cytotoxicity and phototoxicity in the Ce6-embedded SEMS piece with laser irradiation were significantly higher than that of the silicone-covered SEMS with or without laser and the Ce6-embedded silicone-covered SEMS without laser groups (all p < 0.001). Moreover, surface morphology, atomic changes, and homogeneous coverage of the Ce6-embedded silicone-covered membrane were confirmed. The ablation range of the porcine liver was proportionally increased with the irradiation dose (all p < 0.001). The ablation region was identified at different irradiation energy doses of 50, 100, 200, and 400 J/cm2. The in vivo study in the rat esophagus comprised a control group and 100, 200, and 400 J/cm2 energy-dose groups. Finally, histology and immunohistochemistry (TUNEL and Ki67) confirmed that the optimized Ce6-embedded silicone-covered SEMS with selected irradiation energy doses (200 and 400 J/cm2) effectively damaged the esophageal tissue without ductal perforation. The polymeric PS-embedded silicone-covered SEMS can be easily placed via a minimally invasive approach and represents a promising new approach for the palliative treatment of malignant esophageal strictures.


Assuntos
Clorofilídeos , Estenose Esofágica , Fotoquimioterapia , Porfirinas , Stents Metálicos Autoexpansíveis , Humanos , Ratos , Suínos , Animais , Estenose Esofágica/tratamento farmacológico , Estenose Esofágica/cirurgia , Cuidados Paliativos , Silicones , Constrição Patológica/tratamento farmacológico , Porfirinas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico
16.
J Aerosol Med Pulm Drug Deliv ; 37(1): 30-40, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38197850

RESUMO

Background: Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. Methods: In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. Results: Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of -17.23 mV, and in vitro drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, in vitro drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 µm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in in vivo deposition with respect to pure drug deposition, respectively. In vitro drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. Conclusion: PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability.


Assuntos
Nanopartículas , Tuberculose Pulmonar , Humanos , Pirazinamida/uso terapêutico , Administração por Inalação , Sistemas de Liberação de Medicamentos , Tuberculose Pulmonar/tratamento farmacológico , Polímeros/química , Polímeros/uso terapêutico , Nanopartículas/química , Tamanho da Partícula
17.
Sci Rep ; 14(1): 1359, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228631

RESUMO

In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 33. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Humanos , Camundongos , Animais , Adapaleno , Acne Vulgar/tratamento farmacológico , Acne Vulgar/patologia , Pele/patologia , Polímeros/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Resultado do Tratamento , Géis/uso terapêutico
18.
Eur J Pharm Sci ; 192: 106631, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37951316

RESUMO

Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 µg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC0-144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.


Assuntos
Cetorolaco de Trometamina , Nanofibras , Animais , Coelhos , Cetorolaco de Trometamina/uso terapêutico , Anti-Inflamatórios não Esteroides , Inflamação/tratamento farmacológico , Polímeros/uso terapêutico , Soluções Oftálmicas
19.
Adv Mater ; 36(7): e2307940, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37921569

RESUMO

Selective and targeted removal of individual species or strains of bacteria from complex communities can be desirable over traditional and broadly acting antibiotics in several conditions. However, strategies that can detect and ablate bacteria with high specificity are emerging in recent years. Herein, a platform is reported that uses bacteria as a template to synthesize polymers containing guanidinium groups for self-selective depletion of specific pathogenic bacteria without disturbing microbial communities. Different from conventional antibiotics, repeated treatment of bacteria with the templated polymers does not evolve drug resistance mutants after 20 days of serial passaging. Especially, high in vivo therapeutic effectiveness of the templated polymers is achieved in E. coli- and P. aeruginosa-induced microbial peritonitis. The templated polymers have shown high selectivity in in vivo antimicrobial activity, which has excellent potential as systemic antimicrobials against bacterial infections.


Assuntos
Escherichia coli , Polímeros , Polímeros/uso terapêutico , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias
20.
Adv Mater ; 36(1): e2308924, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37864513

RESUMO

Cancer immunotherapy has become a promising method for cancer treatment, bringing hope to advanced cancer patients. However, immune-related adverse events caused by immunotherapy also bring heavy burden to patients. Semiconducting polymer nanoparticles (SPNs) as an emerging nanomaterial with high biocompatibility, can eliminate tumors and induce tumor immunogenic cell death through different therapeutic modalities, including photothermal therapy, photodynamic therapy, and sonodynamic therapy. In addition, SPNs can work as a functional nanocarrier to synergize with a variety of immunomodulators to amplify anti-tumor immune responses. In this review, SPNs-based combination cancer immunotherapy is comprehensively summarized according to the SPNs' therapeutic modalities and the type of loaded immunomodulators. The in-depth understanding of existing SPNs-based therapeutic modalities will hopefully inspire the design of more novel nanomaterials with potent anti-tumor immune effects, and ultimately promote their clinical translation.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Polímeros/uso terapêutico , Semicondutores , Técnicas Fotoacústicas/métodos , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Imunoterapia , Adjuvantes Imunológicos/uso terapêutico , Linhagem Celular Tumoral
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