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1.
J Biomater Sci Polym Ed ; : 1-22, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037962

RESUMO

Burn wounds are associated with infections, drug resistance, allergic reactions, odour, bleeding, excess exudates, and scars, requiring prolonged hospital stay. It is crucial to develop wound dressings that can effectively combat allergic reactions and drug resistance, inhibit infections, and absorb excess exudates to accelerate wound healing. To overcome the above-mentioned problems associated with burn wounds, SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers incorporated with Capparis sepiaria plant extract were prepared using an electrospinning technique. Fourier-transform infrared spectroscopy confirmed the successful incorporation of the extract into the nanofibers without any interaction between the extract and the polymers. The nanofibers displayed porous morphology and a rough surface suitable for cellular adhesion and proliferation. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers demonstrated significant antibacterial effects against wound infection-associated bacterial strains: Pseudomonas aeruginosa, Enterococcus faecalis, Mycobaterium smegmatis, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, and Staphylococcus aureus. Cytocompatibility studies using HaCaT cells revealed the non-toxicity of the nanofibers. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers exhibited hemostatic properties, resulting from the synergistic effect of the plant extract and polymers. The in vitro scratch wound healing assay showed that the SA/PVA/Capparis sepiaria nanofiber wound-healing capability is more than the plant extract and a commercially available wound dressing. The wound-healing potential of SA/PVA/Capparis sepiaria nanofiber is attributed to the synergistic effect of the phytochemicals present in the extract, their porosity, and the ECM-mimicking structure of the nanofibers. The findings suggest that the electrospun nanofibers loaded with Capparis sepiaria extract are promising wound dressings that should be explored for burn wounds.

2.
ACS Omega ; 9(29): 31410-31426, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39072132

RESUMO

Current challenges with ocular drug delivery and the chronic nature of many ocular ailments render the use of traditional ocular devices for additional drug delivery purposes very attractive. To achieve this feat, there is the need to develop biomaterials that are biocompatible, mechanically robust for ocular applications, highly transparent (depending on the targeted ocular device), and with ultralow protein adhesion potential (the primary step in processes that lead to fouling and potential device failure). Herein is reported the facile synthesis of a novel, highly transparent, mechanically robust, nontoxic, bulk functionalized hydrogel with characteristics suited to scalable fabrication of ocular implantable and nonimplantable devices. Synergistic superhydrophilicity between methacrylated poly(vinyl alcohol) (PVAGMA) and zwitterionic sulfobetaine methacrylate was exploited to obtain a superhydrophilic polymer conjugate through facile photoinitiated cross-linking polymerization. Proton nuclear magnetic resonance (1H NMR), attenuated total reflectance-Fourier transform infrared spectroscopy (ATF-FTIR), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to confirm the synthesis and establish the physicochemical parameters for both the starting materials, the conjugated polymer, and the hydrogels. Cytotoxicity and cell adhesion potential evaluated in primary human retinal epithelial cells showed no toxicity or adhesion of the ocular cells. Biofilm adhesion studies in Escherichia coli and Staphylococcus aureus showed over 85% reduction in biofilm adhesion for the best-modified polymer compared to the unconjugated PVAGMA, highlighting its antifouling potential.

3.
Curr Pharm Des ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38910485

RESUMO

Skin cancer is broadly classified into two categories i.e., non-melanoma skin cancer (NMSC) and malignant melanoma (MM), with MM having a greater fatality rate than NMSC. A large number of treatment strategies currently exist for these skin cancer types, ranging from monotherapies to complex multifaceted synergistic interventions including dual therapies, trimodality therapy, and multicomponent combinations therapy. These combinatorial cancer treatments have delivered more favorable results when compared with monotherapies, and although combination treatments increase the cost of treatment, these regimens have lower side effect profiles, decreased resistance, high efficacy and an improved long-term response. Synergistic combination treatments for skin cancer are often complex, wide-ranging and encompass diverse platforms with various mechanisms of action. An understanding of the physiological potential, as well the efficacy of such treatments, is therefore vital to ensure patients receive the best possible treatment. This review therefore focuses on the current advancements and existing non-surgical combinative drug delivery methods utilized for treating skin cancer. It encompasses the diverse pharmaceutical delivery systems, clinical outcomes, and oncology strategies employed and aims to highlight the role of non-surgical combination therapies in enhancing patient compliance, reducing treatment durations, and improving overall survival rates while addressing relapses and metastasis. The promising outlook of the research being conducted in this field has also been provided, as well as the barriers to the effective treatment of this complex condition.

4.
Pharmaceutics ; 16(5)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38794250

RESUMO

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas-Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications.

5.
Int J Pharm ; 657: 124182, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38697584

RESUMO

Despite advances in drug delivery technologies, treating acute respiratory distress syndrome (ARDS) is challenging due to pathophysiological barriers such as lung injury, oedema fluid build-up, and lung inflammation. Active pharmaceutical ingredients (API) can be delivered directly to the lung site of action with the use of aerosol-based drug delivery devices, and this circumvents the hepatic first-pass effect and improves the bioavailability of drugs. This review discusses the various challenges and barriers for pulmonary drug delivery, current interventions for delivery, considerations for effective drug delivery, and the use of nanoparticle drug delivery carriers as potential strategies for delivering therapeutics in ARDS. Nanosystems have the added benefit of entrapping drugs, increase pulmonary drug bioavailability, and using biocompatible and biodegradable excipients that can facilitate targeted and/or controlled delivery. These systems provide an alternative to existing conventional systems. An effective way to deliver drugs for the treatment of ARDS can be by using colloidal systems that are aerosolized or inhaled. Drug distribution to the deeper pulmonary tissues is necessary due to the significant endothelial cell destruction that is prevalent in ARDS. The particle size of nanoparticles (<0.5 µm) makes them ideal candidates for treating ARDS as they can reach the alveoli. A look into the various potential benefits and limitations of nanosystems used for other lung disorders is also considered to indicate how they may be useful for the potential treatment of ARDS.


Assuntos
Sistemas de Liberação de Medicamentos , Pulmão , Nanopartículas , Síndrome do Desconforto Respiratório , Síndrome do Desconforto Respiratório/tratamento farmacológico , Humanos , Sistemas de Liberação de Medicamentos/métodos , Administração por Inalação , Animais , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Aerossóis , Portadores de Fármacos/química
6.
Biomater Adv ; 161: 213870, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38701686

RESUMO

Wound healing following skin tumour surgery still remains a major challenge. To address this issue, polysaccharide-loaded nanofibrous mats have been engineered as skin patches on the wound site to improve wound healing while simultaneously eliminating residual cancer cells which may cause cancer relapse. The marine derived polysaccharides kappa-carrageenan (KCG) and fucoidan (FUC) were blended with polydioxanone (PDX) nanofibers due to their inherent anti-cancer activity conferred by the sulphate groups as well as their immunomodulatory properties which can reduce inflammation resulting in accelerated wound healing. KCG and FUC were released sustainably from the blend nanofibers via the Korsmeyer-Peppas kinetics. MTT assays, live/dead staining and SEM images demonstrated the toxicity of KCG and FUC towards skin cancer MP 41 cells. In addition, MP 41 cells showed reduced metastatic potential when grown on KCG or FUC containing mats. Both KCG and FUC were non- cytotoxic to healthy L 929 fibroblast cells. In vivo studies on healthy Wistar rats confirmed the non-toxicity of the nanofibrous patches as well as their improved and scarless wound healing potential. In vivo studies on tumour xenograft model further showed a reduction of 7.15 % in tumour volume in only 4 days following application of the transdermal patch.


Assuntos
Melanoma , Nanofibras , Polissacarídeos , Ratos Wistar , Neoplasias Cutâneas , Alicerces Teciduais , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Nanofibras/química , Ratos , Neoplasias Cutâneas/patologia , Melanoma/patologia , Alicerces Teciduais/química , Polissacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Camundongos , Linhagem Celular Tumoral , Carragenina/farmacologia , Humanos , Polidioxanona/farmacologia , Polidioxanona/química , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia
7.
Expert Opin Drug Deliv ; : 1-14, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722022

RESUMO

INTRODUCTION: Three-Dimensional (3D) microneedles have recently gained significant attention due to their versatility, biocompatibility, enhanced permeation, and predictable behavior. The incorporation of biological agents into these 3D constructs has advanced the traditional microneedle into an effective platform for wide-ranging applications. AREAS COVERED: This review discusses the current state of microneedle fabrication as well as the developed 3D printed microneedles incorporating labile pharmaceutical agents and biological materials for potential biomedical applications. The mechanical and processing considerations for the preparation of microneedles and the barriers to effective 3D printing of microneedle constructs have additionally been reviewed along with their therapeutic applications and potential for tissue engineering and regenerative applications. Additionally, the regulatory considerations for microneedle approval have been discussed as well as the current clinical trial and patent landscapes. EXPERT OPINION: The fields of tissue engineering and regenerative medicine are evolving at a significant pace with researchers constantly focused on incorporating advanced manufacturing techniques for the development of versatile, complex, and biologically specific platforms. 3D bioprinted microneedles, fabricated using conventional 3D printing techniques, have resultantly provided an alternative to 2D bioscaffolds through the incorporation of biological materials within 3D constructs while providing further mechanical stability, increased bioactive permeation and improved innervation into surrounding tissues. This advancement therefore potentially allows for a more effective biomimetic construct with improved tissue-specific cellular growth for the enhanced treatment of physiological conditions requiring tissue regeneration and replacement.

8.
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
9.
Drug Deliv Transl Res ; 14(10): 2668-2694, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38519828

RESUMO

This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153 nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.


Assuntos
Ácido Hialurônico , Hidrogéis , Nanopartículas , Triancinolona Acetonida , Corpo Vítreo , Animais , Coelhos , Nanopartículas/administração & dosagem , Nanopartículas/química , Hidrogéis/química , Hidrogéis/administração & dosagem , Ácido Hialurônico/química , Ácido Hialurônico/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/química , Triancinolona Acetonida/farmacocinética , Corpo Vítreo/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Poloxâmero/química , Camundongos , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Segmento Posterior do Olho/efeitos dos fármacos , Humanos , Linhagem Celular , Injeções Intravítreas , Ácido Poliglicólico/química , Ácido Poliglicólico/administração & dosagem
10.
J Biomed Mater Res B Appl Biomater ; 112(2): e35376, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38359173

RESUMO

Calvarial defects of bone present difficult clinical situations, and their restoration using biocompatible materials requires special treatments that enable bone regeneration. Magnesium phosphate (MgP) is known as an osteoinductive biomaterial because it contains Mg2+ ions and P ions that enhance the activity of osteoplast cells and help in bone regeneration. In this study, MgP and CuO-doped MgP were fabricated and characterized for their physicomechanical properties, particle size, morphology, surface area, antibacterial test, and in vitro bioactivity evaluation using the following techniques: X-rays diffraction, Fourier-transformer infrared, TEM, and Brunauer, Emmett and Teller (BET) surface area, X-rays photoelectron spectroscopy (XPS), and Scanning electron microscopy (SEM). Furthermore, these nanopowders were implanted in adult inbred male Wistar rats and studied after two periods (28 and 56 days). The results demonstrated that the obtained semiamorphous powders are in nanoscale (≤ 50 nm). XPS analysis ensured the preparation of MgP as mono MgP and CuO were incorporated in the structure as Cu2+ . The bioactivity was supported by the observation of calcium phosphate layer on the nanopowders' surface. The in vivo study demonstrated success of MgP nanopowders especially those doped with CuO in restoration of calvarial defect bone. Therefore, fabricated biomaterials are of great potential in restoration of bone calvarial defects.


Assuntos
Osso e Ossos , Cobre , Compostos de Magnésio , Ratos , Animais , Masculino , Cobre/farmacologia , Cobre/química , Ratos Wistar , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Fosfatos/farmacologia
11.
AAPS PharmSciTech ; 25(1): 15, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200167

RESUMO

This research aimed to explore the possibilities of Eudragit S100 (ES100) and sodium alginate as carriers for tenofovir disoproxil fumarate (TDF) in the female genital tract. Alginate and alginate-ES100 nanoparticles were prepared using the ionic gelation and emulsion/gelation complexation method, respectively. The nanocarriers were tested using morphological, physicochemical, in vitro drug release, and cytotoxicity analyses. In SEM and TEM images, the presence of spherical and uniformly distributed nanoparticles was revealed. The FTIR spectrum showed that alginate and calcium chloride interacted due to ionic bonds linking divalent calcium ions and the -COO- of alginate groups. Alginate and ES100 interacted via the ester C=O amide stretching. The results obtained from XRD and DSC, on the other hand, revealed a favorable interaction between sodium alginate and ES100 polymers, as evidenced by the crystallization peaks observed. Under experimental design analysis and optimization, overall size distribution profiles ranged from 134.9 to 228.0 nm, while zeta potential results showed stable nanoparticles (-17.8 to -38.4 MV). The optimal formulation exhibited a maximum cumulative in vitro release of 72% (pH 4.2) up to 96 h. The cytotoxicity tests revealed the safety of TDF-loaded nanoparticles on vaginal epithelial cells at concentrations of 0.025 mg/mL, 0.5 mg/mL, and 1 mg/mL for 72 h. These results indicated that alginate-ES100 nanoparticles have the potential to preserve and sustain the release of the TDF drug in the FGT. The future goal is to develop a low-dose non-toxic microbicide that can be administered long term in the vagina to cater to both pregnant and non-pregnant HIV patients.


Assuntos
Infecções por HIV , Ácidos Polimetacrílicos , Gravidez , Feminino , Humanos , Tenofovir , Infecções por HIV/tratamento farmacológico , Genitália Feminina , Alginatos
12.
ACS Omega ; 9(1): 700-713, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222506

RESUMO

The design of targeted antiangiogenic nanovectors for the delivery of anticancer drugs presents a viable approach for effective management of nonsmall-cell lung carcinoma (NSCLC). Herein, we report on the fabrication of a targeted delivery nanosystem for paclitaxel (PTX) functionalized with a short antimatrix metalloproteinase 2 (MMP-2) CTT peptide for selective MMP-2 targeting and effective antitumor activity in NSCLC. The fabrication of the targeted nanosystem (CLA-coated PTX-SPIONs@CTT) involved coating of superparamagnetic iron-oxide nanoparticles (SPIONs) with conjugated linoleic acid (CLA) via chemisorption, onto which PTX was adsorbed, and subsequent surface functionalization with carboxylic acid groups for conjugation of the CTT peptide. CLA-coated PTX SPIONs@CTT had a mean particle size of 99.4 nm and a PTX loading efficiency of ∼98.5%. The nanosystem exhibited a site-specific in vitro PTX release and a marked antiproliferative action on lung adenocarcinoma cells. The CTT-functionalized nanosystem significantly inhibited MMP-2 secretion by almost 70% from endothelial cells, indicating specific anti-MMP-2 activity. Treatment of tumor-bearing mice with subcutaneous injection of the CTT-functionalized nanosystem resulted in 69.7% tumor inhibition rate, and the administration of the nanosystem subcutaneously prolonged the half-life of PTX and circulation time in vivo. As such, CLA-coated PTX-SPIONs@CTT presents with potential for application as a targeted nanomedicine in NSCLC management.

13.
Curr Pharm Des ; 29(40): 3187-3205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779402

RESUMO

The physicochemical properties of polymeric hydrogels render them attractive for the development of 3D printed prototypes for tissue engineering in regenerative medicine. Significant effort has been made to design hydrogels with desirable attributes that facilitate 3D printability. In addition, there is significant interest in exploring stimuli-responsive hydrogels to support automated 3D printing into more structurally organised prototypes such as customizable bio-scaffolds for regenerative medicine applications. Synthesizing stimuli-responsive hydrogels is dependent on the type of design and modulation of various polymeric materials to open novel opportunities for applications in biomedicine and bio-engineering. In this review, the salient advances made in the design of stimuli-responsive polymeric hydrogels for 3D printing in tissue engineering are discussed with a specific focus on the different methods of manipulation to develop 3D printed stimuli-responsive polymeric hydrogels. Polymeric functionalisation, nano-enabling and crosslinking are amongst the most common manipulative attributes that affect the assembly and structure of 3D printed bio-scaffolds and their stimuli- responsiveness. The review also provides a concise incursion into the various applications of stimuli to enhance the automated production of structurally organized 3D printed medical prototypes.


Assuntos
Medicina Regenerativa , Engenharia Tecidual , Humanos , Hidrogéis/química , Impressão Tridimensional , Alicerces Teciduais
14.
AAPS PharmSciTech ; 24(7): 201, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37783896

RESUMO

Neurovascular diseases are linked to the brain's blood vessels. These disorders are complicated to treat due to the strict selective characteristics of the blood-brain barrier. Consequently, the potency of the pharmacological treatments for these conditions is immensely diminished, leading to a rise in neurovascular-associated morbidity and mortality. Carbon nanotubes are regarded as essential nanoparticles with a promise of treating neurovascular disorders. Current findings have demonstrated the effectiveness of carbon nanotubes as vehicles for ferrying drugs to the site of interest. This review accentuates the theoretical utilisation of carbon nanotubes as drug nanocarriers equipped with the penetrating capability to the blood-brain barrier for treating neurovascular disorders such as ischemic stroke. The success of the carbon nanotube system may result in the development of a new and highly relevant drug delivery procedure. This review will also cover carbon nanotube functionalisation for applications in the biomedical fields, toxicity, in vitro and in vivo drugs and biomolecule delivery, and the future outlook of carbon nanotubes.


Assuntos
Nanotubos de Carbono , Sistemas de Liberação de Medicamentos , Barreira Hematoencefálica , Transporte Biológico , Preparações Farmacêuticas , Excipientes
15.
Biomedicines ; 11(9)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37760986

RESUMO

The optimal treatment of diabetes (in particular, type 1 diabetes-T1D) remains a challenge. Closed-loop systems (implants/inserts) provide significant advantages for glucose responsivity and providing real-time sustained release of rapid-acting insulin. Concanavalin A (ConA), a glucose affinity agent, has been used to design closed-loop insulin delivery systems but not without significant risk of leakage of ConA from the matrices and poor mechanical strength of the hydrogels impacting longevity and control of insulin release. Therefore, this work focused on employing a thermoresponsive co-forming matrix between Pluronic F-127 (PL) and structurally robust chitosan (CHT) via EDC/NHS coupling (i.e., covalent linkage of -NH2 from CHT and ConA to the -COOH of PL). The system was characterized for its chemical structure stability and integrity (FTIR, XRD and TGA), injectability, rheological parameters and hydrogel morphology (Texture Analysis, Elastosens TM Bio2 and SEM). The prepared hydrogels demonstrated shear-thinning for injectability with a maximum force of 4.9 ± 8.3 N in a 26G needle with sol-gel transitioning from 25 to 38 °C. The apparent yield stress value of the hydrogel was determined to be 67.47 Pa. The insulin loading efficiency within the hydrogel matrix was calculated to be 46.8%. Insulin release studies revealed glucose responsiveness in simulated glycemic media (4 and 10 mg/mL) over 7 days (97%) (305 nm via fluorescence spectrophotometry). The MTT studies were performed over 72 h on RIN-5F pancreatic cells with viability results >80%. Results revealed that the thermoresponsive hydrogel is a promising alternative to current closed-loop insulin delivery systems.

16.
Biomedicines ; 11(7)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37509497

RESUMO

The purpose of the study was to synthesize and investigate the influence of geometrical structure, magnetism, and cytotoxic activity on core-shell platinum and iron-platinum (Fe/Pt) composite nanowires (NWs) for potential application in targeted chemotherapeutic approaches. The Pt-NWs and Fe/Pt composite NWs were synthesized via template electrodeposition, using anodic aluminum oxide (AAO) membranes. The Fe/Pt composite NWs (Method 1) was synthesized using two electrodeposition steps, allowing for greater control of the diameter of the NW core. The Fe/Pt composite NWs (Method 2) was synthesized by pulsed electrodeposition, using a single electrolytic bath. The properties of the synthesized NWs were assessed by high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, powder X-ray diffraction (XRD), inductively coupled plasma-optical emission spectrometry (ICP-OES), vibrating-sample magnetometry (VSM), and surface charge (zeta potential). A microscopy image analysis of the NWs revealed the presence of high-aspect-ratio NWs with nominal diameters of 40-50 nm and lengths of approximately <4 µm. The obtained powder XRD patterns confirmed the presence of a polycrystalline structure for both Pt NWs and Fe/Pt composite NWs. The potential utility of the synthesized NW nanoplatforms for anticancer activity was investigated using Tera 1 cells and Mouse 3T3 cells. Pt-NWs displayed modest cytotoxic activity against Tera 1 cells, while the Fe/Pt composite NWs (both Methods 1 and 2) demonstrated enhanced cytotoxic activity compared to the Pt-NWs on Tera 1 cells. The Fe/Pt composite NWs (Method 1) displayed ferromagnetic behavior and enhanced cytotoxic activity compared to Pt-NWs on Tera 1 cells, thus providing a sound basis for future magnetically targeted chemotherapeutic applications.

17.
Lancet Infect Dis ; 23(8): e288-e300, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37290473

RESUMO

The COVID-19 pandemic heralded unprecedented resource mobilisation and global scientific collaboration to rapidly develop effective vaccines. Regrettably, vaccine distribution has been inequitable, particularly in Africa where manufacturing capacity remains nominal. To address this, several initiatives are underway to develop and manufacture COVID-19 vaccines in Africa. Nevertheless, diminishing demand for COVID-19 vaccines, the cost competitiveness of producing goods locally, intellectual property rights issues, and complex regulatory environments among other challenges can undermine these ventures. We outline how extending COVID-19 vaccine manufacturing in Africa to include diverse products, multiple vaccine platforms, and advanced delivery systems will ensure sustainability. Possible models, including leveraging public-academic-private partnerships to enhance success of vaccine manufacturing capacity in Africa are also discussed. Intensifying research in vaccine discovery on the continent could yield vaccines that further bolster sustainability of local production, ensuring greater pandemic preparedness in resource-constrained environments, and long-term health systems security.


Assuntos
COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19 , Pandemias/prevenção & controle , COVID-19/prevenção & controle , África/epidemiologia
18.
ACS Appl Bio Mater ; 6(7): 2747-2759, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37384895

RESUMO

A design has been established for the surface decoration of superparamagnetic iron oxide nanoparticles (SPIONs) with anti-vascular endothelial growth factor peptide, HRH, to formulate a targeted paclitaxel (PTX) delivery nanosystem with notable tumor targetability and antiangiogenic activity. The design methodology included (i) tandem surface functionalization via coupling reactions, (ii) pertinent physicochemical characterization, (iii) in vitro assessment of drug release, anti-proliferative activity, and quantification of vascular endothelial growth factor A (VEGF-A) levels, and (iv) in vivo testing using a lung tumor xenograft mouse model. Formulated CLA-coated PTX-SPIONs@HRH depicted a size and surface charge of 108.5 ± 3.5 nm and -30.4 ± 2.3 mV, respectively, and a quasi-spherical shape relative to pristine SPIONs. Fourier transform infrared (FTIR) analysis and estimation of free carboxylic groups supported the preparation of the CLA-coated PTX-SPIONs@HRH. CLA-coated PTX-SPIONs@HRH exhibited high PTX loading efficiency (98.5%) and sustained release in vitro, with a marked dose dependent anti-proliferative activity in A549 lung adenocarcinoma cells, complimented by an enhanced cellular uptake. CLA-coated PTX-SPIONs@HRH significantly reduced secretion levels of VEGF-A in human dermal microvascular endothelial cells from 46.9 to 35.6 pg/mL compared to untreated control. A 76.6% tumor regression was recorded in a lung tumor xenograft mouse model following intervention with CLA-coated PTX-SPIONs@HRH, demonstrating tumor targetability and angiogenesis inhibition. CLA-coated PTX-SPIONs@HRH enhanced the half-life of PTX by almost 2-folds and demonstrated a prolonged PTX plasma circulation time from a subcutaneous injection (SC). Thus, it is suggested that CLA-coated PTX-SPIONs@HRH could provide a potential effective treatment modality for non-small-cell lung carcinoma as a nanomedicine.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Células Endoteliais , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral , Peptídeos/química , Nanopartículas Magnéticas de Óxido de Ferro
19.
Biomedicines ; 11(4)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37189819

RESUMO

Nanoparticles are designed to entrap drugs at a high concentration, escape clearance by the immune system, be selectively taken up by cancer cells, and release bioactives in a rate-modulated manner. In this study, quercetin-loaded PLGA nanoparticles were prepared and optimized to determine whether coating with chitosan would increase the cellular uptake of the nanoparticles and if the targeting ability of folic acid as a ligand can provide selective toxicity and enhanced uptake in model LnCap prostate cancer cells, which express high levels of the receptor prostate-specific membrane antigen (PSMA), compared to PC-3 cells, that have relatively low PSMA expression. A design of experiments approach was used to optimize the PLGA nanoparticles to have the maximum quercetin loading, optimal cationic charge, and folic acid coating. We examined the in vitro release of quercetin and comparative cytotoxicity and cellular uptake of the optimized PLGA nanoparticles and revealed that the targeted nano-system provided sustained, pH-dependent quercetin release, and higher cytotoxicity and cellular uptake, compared to the non-targeted nano-system on LnCap cells. There was no significant difference in the cytotoxicity or cellular uptake between the targeted and non-targeted nano-systems on PC-3 cells (featured by low levels of PSMA), pointing to a PSMA-specific mechanism of action of the targeted nano-system. The findings suggest that the nano-system can be used as an efficient nanocarrier for the targeted delivery and release of quercetin (and other similar chemotherapeutics) against prostate cancer cells.

20.
Ther Deliv ; 14(2): 139-156, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-37125434

RESUMO

Aim: Essential oils are promising antibacterial and wound-healing agents that should be explored for the design of wound dressings. Materials & methods: Topical gels prepared from a combination of carboxymethyl cellulose and poloxamer were incorporated with tea tree and lavender oil together with Ag nanoparticles. In vitro release, cytotoxicity, antibacterial, and wound healing studies were performed. Results: The gels displayed good spreadability with viscosity in the range of 210-1200 cP. The gels displayed promising antibacterial activity against selected Gram-positive and Gram-negative bacteria used in the study. The % cell viability of the gels was more than 90.83%. Conclusion: The topical gels displayed excellent wound closure in vitro revealing that they are potential wound dressings for bacteria-infected wounds.


What is this article about? This article reports the efficacy of carboxymethyl cellulose-based topical gels loaded with a combination of essential oils and silver nanoparticles as potential wound dressings for bacterial-infected wounds. What were the results? The topical gels induced a faster rate of closure than the untreated cells in 96 h. The gel formulations did not induce any significant cytotoxic effect. They were effective against Gram-negative and Gram-positive bacteria used in the study. What do the results of the study mean? The topical gels displayed promising healing effects in vitro revealing that they are potential wound dressings for treating bacteria-infected wounds.


Assuntos
Nanopartículas Metálicas , Óleos Voláteis , Antibacterianos/farmacologia , Carboximetilcelulose Sódica , Poloxâmero , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Prata , Bandagens , Óleos Voláteis/farmacologia , Géis
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