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1.
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
2.
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.

3.
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
4.
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
5.
Int J Mol Sci ; 24(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37108772

RESUMO

This research aimed to substantiate the potential practicality of utilizing a matrix-like platform, a novel 3D-printed biomaterial scaffold, to enhance and guide host cells' growth for bone tissue regeneration. The 3D biomaterial scaffold was successfully printed using a 3D Bioplotter® (EnvisionTEC, GmBH) and characterized. Osteoblast-like MG63 cells were utilized to culture the novel printed scaffold over a period of 1, 3, and 7 days. Cell adhesion and surface morphology were examined using scanning electron microscopy (SEM) and optical microscopy, while cell viability was determined using MTS assay and cell proliferation was evaluated using a Leica microsystem (Leica MZ10 F). The 3D-printed biomaterial scaffold exhibited essential biomineral trace elements that are significant for biological bone (e.g., Ca-P) and were confirmed through energy-dispersive X-ray (EDX) analysis. The microscopy analyses revealed that the osteoblast-like MG63 cells were attached to the printed scaffold surface. The viability of cultured cells on the control and printed scaffold increased over time (p < 0.05); however, on respective days (1, 3, and 7 days), the viability of cultured cells between the two groups was not significantly different (p > 0.05). The protein (human BMP-7, also known as growth factor) was successfully attached to the surface of the 3D-printed biomaterial scaffold as an initiator of osteogenesis in the site of the induced bone defect. An in vivo study was conducted to substantiate if the novel printed scaffold properties were engineered adequately to mimic the bone regeneration cascade using an induced rabbit critical-sized nasal bone defect. The novel printed scaffold provided a potential pro-regenerative platform, rich in mechanical, topographical, and biological cues to guide and activate host cells toward functional regeneration. The histological studies revealed that there was progress in new bone formation, especially at week 8 of the study, in all induced bone defects. In conclusion, the protein (human BMP-7)-embedded scaffolds showed higher regenerative bone formation potential (week 8 complete) compared to the scaffolds without protein (e.g., growth factor; BMP-7) and the control (empty defect). At 8 weeks postimplantation, protein (BMP-7) significantly promoted osteogenesis as compared to other groups. The scaffold underwent gradual degradation and replacement by new bones at 8 weeks in most defects.


Assuntos
Materiais Biocompatíveis , Engenharia Tecidual , Animais , Humanos , Coelhos , Materiais Biocompatíveis/farmacologia , Alicerces Teciduais , Proteína Morfogenética Óssea 7 , Osteogênese , Regeneração Óssea , Impressão Tridimensional
6.
Curr Drug Deliv ; 20(10): 1487-1503, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35959905

RESUMO

BACKGROUND: Currently, the treatment protocols for tuberculosis (TB) have several challenges, such as inconsistent oral bioavailability, dose-related adverse effects, and off-target drug toxicity. METHODS: This research reports the design and characterization of rifampicin (RIF) and isoniazid (INH) loaded hybrid lipid-polysaccharide nanoparticles using the solvent injection method, and demonstrated the influence of conjugated mannosyl residue on macrophage targeting and intracellular drug delivery capacity. RESULTS: The nanospheres, herein called mannose-decorated lipopolysaccharide nanoparticles, were spherical in shape, exhibiting average sizes less than 120 nm (PDI<0.20) and positive zeta potentials. Drug encapsulation was greater than 50% for rifampicin and 60% for isoniazid. The pH-responsive drug release was sustained over a 48-hour period and preferentially released more rifampicin/isoniazid in a simulated acidic phagolysosomal environment (pH 4.8) than in a simulated physiological medium. TGA and FTIR analysis confirmed successful mannose-grafting on nanoparticle surface and optimal degree of mannosylation was achieved within 48-hour mannose-lipopolysaccharide reaction time. The mannosylated nanoparticles were biocompatible and demonstrated a significant improvement towards uptake by RAW 264.7 cells, producing higher intracellular RIF/INH accumulation when compared to the unmannosylated nanocarriers. CONCLUSION: Overall, the experimental results suggested that mannose-decorated lipopolysaccharide nanosystems hold promise towards safe and efficacious macrophage-targeted delivery of anti-TB therapeutics.


Assuntos
Nanopartículas , Nanosferas , Tuberculose , Humanos , Rifampina/farmacologia , Isoniazida/farmacologia , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/uso terapêutico , Manose/uso terapêutico , Tuberculose/tratamento farmacológico , Macrófagos , Nanopartículas/química
7.
Molecules ; 27(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36364474

RESUMO

A series of new 1,2,4-triazolo-linked bis-indolyl conjugates (15a-r) were prepared by multistep synthesis and evaluated for their cytotoxic activity against various human cancer cell lines. It was observed that they were more susceptible to colon and breast cancer cells. Conjugates 15o (IC50 = 2.04 µM) and 15r (IC50 = 0.85 µM) illustrated promising cytotoxicity compared to 5-fluorouracil (5-FU, IC50 = 5.31 µM) against the HT-29 cell line. Interestingly, 15o and 15r induced cell cycle arrest at the G0/G1 phase and disrupted the mitochondrial membrane potential. Moreover, these conjugates led to apoptosis in HT-29 at 2 µM and 1 µM, respectively, and also enhanced the total ROS production as well as the mitochondrial-generated ROS. Immunofluorescence and Western blot assays revealed that these conjugates reduced the expression levels of the PI3K-P85, ß-catenin, TAB-182, ß-actin, AXIN-2, and NF-κB markers that are involved in the ß-catenin pathway of colorectal cancer. The results of the in silico docking studies of 15r and 15o further support their dual inhibitory behaviour against PI3K and tankyrase. Interestingly, the conjugates have adequate ADME-toxicity parameters based on the calculated results of the molecular dynamic simulations, as we found that these inhibitors (15r) influenced the conformational flexibility of the 4OA7 and 3L54 proteins.


Assuntos
Antineoplásicos , Tanquirases , Humanos , beta Catenina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células , Antineoplásicos/farmacologia , Apoptose , Fluoruracila/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular
8.
Int J Mol Sci ; 23(16)2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36012770

RESUMO

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs' suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.


Assuntos
Nanopartículas , Praziquantel , Animais , Modelos Animais de Doenças , Portadores de Fármacos/química , Lipídeos/química , Lipossomos , Camundongos , Nanopartículas/química , Tamanho da Partícula , Praziquantel/química , Praziquantel/farmacologia , Praziquantel/uso terapêutico
9.
Pharmaceutics ; 14(4)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35456663

RESUMO

The application of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as a nanomedicine for Non-Small Cell Lung Carcinoma (NSCLC) can provide effective delivery of anticancer drugs with minimal side-effects. SPIONs have the flexibility to be modified to achieve enhanced oading of hydrophobic anticancer drugs such as paclitaxel (PTX). The purpose of this study was to synthesize novel trans-10, cis-12 conjugated linoleic acid (CLA)-coated SPIONs loaded with PTX to enhance the anti-proliferative activity of PTX. CLA-coated PTX-SPIONs with a particle size and zeta potential of 96.5 ± 0.6 nm and -27.3 ± 1.9 mV, respectively, were synthesized. The superparamagnetism of the CLA-coated PTX-SPIONs was confirmed, with saturation magnetization of 60 emu/g and 29 Oe coercivity. CLA-coated PTX-SPIONs had a drug loading efficiency of 98.5% and demonstrated sustained site-specific in vitro release of PTX over 24 h (i.e., 94% at pH 6.8 mimicking the tumor microenvironment). Enhanced anti-proliferative activity was also observed with the CLA-coated PTX-SPIONs against a lung adenocarcinoma (A549) cell line after 72 h, with a recorded cell viability of 17.1%. The CLA-coated PTX-SPIONs demonstrated enhanced suppression of A549 cell proliferation compared to pristine PTX, thus suggesting potential application of the nanomedicine as an effective site-specific delivery system for enhanced therapeutic activity in NSCLC therapy.

10.
J Biomed Mater Res B Appl Biomater ; 110(10): 2189-2210, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35373911

RESUMO

In this research, a novel bioabsorbable suture that is, monofilament and capable of localized drug delivery, was developed from a combination of natural biopolymers that where not previously applied for this purpose. The optimized suture formulation comprised of sodium alginate (6% wt/vol), pectin (0.1% wt/vol), and gelatin (3% wt/vol), in the presence of glycerol (4% vol/vol) which served as a plasticizer. The monofilament bioabsorbable sutures where synthesized via in situ ionic crosslinking in a barium chloride solution (2% wt/vol). The resulting suture was characterized in terms of mechanical properties, morphology, swelling, degradation, drug release, and biocompatibility, in addition to Fourier-transform infrared (FTIR) spectroscopy, Powder X-ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC) analysis. The drug loaded and non-drug loaded sutures had a maximum breaking strength of 4.18 and 4.08 N, in the straight configuration and 2.44 N and 2.59 N in the knot configuration, respectively. FTIR spectrum of crosslinked sutures depicted Δ9 cm-1 downward shift for the carboxyl stretching band which was indicative of ionic interactions between barium ions and sodium alginate. In vitro analysis revealed continued drug release for 7 days and gradual degradation by means of surface erosion, which was completed by day 28. Biocompatibility studies revealed excellent hemocompatibility and no cytotoxicity. These results suggest that the newly developed bioabsorbable suture meets the basic requirements of a suture material and provides a viable alternative to the synthetic polymer sutures that are currently on the market.


Assuntos
Implantes Absorvíveis , Suturas , Alginatos , Polímeros , Técnicas de Sutura , Resistência à Tração
11.
Bioorg Med Chem ; 58: 116652, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35180594

RESUMO

The toxicity of existing anticancer agents on healthy cells and the emergence of multidrug-resistance cancer cells have led to the search for less toxic anticancer agents with different mechanisms of action. In this study, a novel class of ferrocenylbisphosphonate hybrid compounds (H1-H8) were designed and characterized using NMR, IR and HRMS. The in vitro anticancer activity of the hybrid compounds on HeLa (cervix adenocarcinoma) and A549 (non-small cell lung cancer cell lines) was evaluated. The structure-activity relationship of the hybrid molecules was also studied. The lead compound, tetraethyl (3-(4-oxo-4-ferrocenylbutanamido) propane-1-1-diylbis(phosphonate) (H6) exhibited higher cytotoxicity on A549 (IC50 = 28.15 µM) than cisplatin (IC50 = 58.28 µM), while its activity on HeLa cells (IC50 = 14.69 µM) was equivalent to that of cisplatin 15.10 µM (HeLa cells). H6 (IC50 = 95.58 µM) was also five times less toxic than cisplatin (IC50 = 20.86 µM) on fibroblast NIH3T3 suggesting that H6 can be a future replacement for cisplatin due to its non-toxicity to healthy cells. Interestingly, some ferrocene and bisphosphonate parent compounds exhibited promising anticancer activity with 4-ferrocenyl-4-oxobutanoic acid (FI) exhibiting higher cytotoxic activity (IC50 = 1.73 µM) than paclitaxel (IC50 = 3.5 µM) on A549 cell lines. F1 also exhibited lower cytotoxicity than paclitaxel and cisplatin on the normal murine fibroblast cell line (NIH3T3). The molecular docking studies showed H6 strong binding affinity for the STAT3 signaling pathway in A549 cell line, and the MAdCAM-1 and cellular tumor antigen p53 proteins in HeLa cell lines.


Assuntos
Antineoplásicos/farmacologia , Difosfonatos/farmacologia , Compostos Ferrosos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Difosfonatos/síntese química , Difosfonatos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Ferrosos/síntese química , Compostos Ferrosos/química , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
12.
Pharmaceutics ; 14(2)2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35214173

RESUMO

Traumatic brain injuries (TBIs) are still a challenge for the field of modern medicine. Many treatment options such as autologous grafts and stem cells show limited promise for the treatment and the reversibility of damage caused by TBIs. Injury beyond the critical size necessitates the implementation of scaffolds that function as surrogate extracellular matrices. Two scaffolds were synthesised utilising polysaccharides, chitosan and hyaluronic acid in conjunction with gelatin. Both scaffolds were chemically crosslinked using a naturally derived crosslinker, Genipin. The polysaccharides increased the mechanical strength of each scaffold, while gelatin provided the bioactive sequence, which promoted cellular interactions. The effect of crosslinking was investigated, and the crosslinked hydrogels showed higher thermal decomposition temperatures, increased resistance to degradation, and pore sizes ranging from 72.789 ± 16.85 µm for the full interpenetrating polymer networks (IPNs) and 84.289 ± 7.658 µm for the semi-IPN. The scaffolds were loaded with Dexamethasone-21-phosphate to investigate their efficacy as a drug delivery vehicle, and the full IPN showed a 100% release in 10 days, while the semi-IPN showed a burst release in 6 h. Both scaffolds stimulated the proliferation of rat pheochromocytoma (PC12) and human glioblastoma multiforme (A172) cell cultures and also provided signals for A172 cell migration. Both scaffolds can be used as potential drug delivery vehicles and as artificial extracellular matrices for potential neural regeneration.

13.
Polymers (Basel) ; 13(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34372008

RESUMO

In many clinical applications, the transdermal route is used as an alternative approach to avoid the significant limitations associated with oral drug delivery. There is a long history for drug delivery through the skin utilizing transdermal microneedle arrays. Microneedles are reported to be versatile and very efficient devices. This technique has spurred both industrial and scientific curiosity, due to its outstanding characteristics such as painless penetration, affordability, excellent medicinal efficiency, and relative protection. Microneedles possess outstanding properties for diverse biomedical uses such as the delivery of very large substances with ionic and hydrophilic physicochemical properties. Importantly, microneedles are applicable in numerous biomedical fields such as therapy, diagnosis, and vaccine administration. Microneedles are emerging tools that have shown profound potential for biomedical applications. Transdermal microneedle technologies are likely to become a preferred route of therapeutic substances administration in the future since they are effective, painless, and affordable. In this review, we summarize recent advances in microneedles for therapeutic applications. We explore their constituent materials and fabrication methods that improve the delivery of critical therapeutic substances through the skin. We further discuss the practicality of advanced microneedles used as drug delivery tools.

14.
Polymers (Basel) ; 13(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946703

RESUMO

Nanotechnology has aided in the advancement of drug delivery for the treatment of several neurological disorders including depression. Depression is a relatively common mental disorder which is characterized by a severe imbalance of neurotransmitters. Several current therapeutic regimens against depression display drawbacks which include low bioavailability, delayed therapeutic outcome, undesirable side effects and drug toxicity due to high doses. The blood-brain barrier limits the entry of the drugs into the brain matrix, resulting in low bioavailability and tissue damage due to drug accumulation. Due to their size and physico-chemical properties, nanotechnological drug delivery systems present a promising strategy to enhance the delivery of nanomedicines into the brain matrix, thereby improving bioavailability and limiting toxicity. Furthermore, ligand-complexed nanocarriers can improve drug specificity and antidepressant efficacy and reduce drug toxicity. Biopolymers and nanocarriers can also be employed to enhance controlled drug release and reduce the hepatic first-pass effect, hence reducing the dosing frequency. This manuscript reviews recent advances in different biopolymers, such as polysaccharides and other nanocarriers, for targeted antidepressant drug delivery to the brain. It probes nano-based strategies that can be employed to enhance the therapeutic efficacy of antidepressants through the oral, intranasal, and parenteral routes of administration.

15.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805969

RESUMO

The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.


Assuntos
Sistemas de Liberação de Medicamentos , Substâncias Macromoleculares/química , Nanomedicina/métodos , Compostos Azo , Portadores de Fármacos/química , Humanos , Ácido Hialurônico/química , Hidrogéis/química , Imunoglobulina G/química , Injeções , Iridoides/química , Luz , Nanosferas/química , Tamanho da Partícula , Fototerapia/métodos , Prolaminas/química , Reologia , Temperatura , Difração de Raios X
16.
PLoS One ; 14(9): e0222614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560702

RESUMO

The Warburg Effect has emerged as a potential drug target because, in some cancer cell lines, it is sufficient to subvert it in order to kill cancer cells. It has also been shown that the Warburg Effect occurs in innate immune cells upon infection. Innate immune cells play critical roles in the tumour microenvironment but the Warburg Effect is not fully understood in monocytes. Furthermore, it is important to understand the impact of infections on key players in the tumour microenvironment because inflammatory conditions often precede carcinogenesis and mutated oncogenes induce inflammation. We investigated the metabolic programme in the acute monocytic leukaemia cell line, THP-1 in the presence and absence of lipopolysaccharide, mimicking bacterial infections. We found that stimulation of THP-1 cells by LPS induces a subset of pro-inflammatory chemokines and enhances the Warburg Effect. Surprisingly, perturbation of the Warburg Effect in these cells does not lead to cell death in contrast to what was observed in non-myeloid cancer cell lines in a previous study. These findings indicate that the Warburg Effect and inflammation are activated by bacterial lipopolysaccharide and may have a profound influence on the microenvironment.


Assuntos
Quimiocinas/metabolismo , Glicólise , Lipopolissacarídeos/farmacologia , Neoplasias/metabolismo , Fosforilação Oxidativa , Receptor 4 Toll-Like/metabolismo , Apoptose , Humanos , Potencial da Membrana Mitocondrial , Consumo de Oxigênio , Transdução de Sinais/efeitos dos fármacos , Células THP-1
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