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1.
J Infect Public Health ; 17(5): 906-917, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569270

RESUMO

BACKGROUND: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. METHODS: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. RESULTS: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. CONCLUSION: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.


Assuntos
Quitosana , Glicolatos , Nanopartículas , Pneumonia , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ácido Poliglicólico/química , Levofloxacino/farmacologia , Quitosana/química , Glicóis , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Ácido Láctico/química , Antibacterianos/farmacologia , Bactérias/metabolismo , Nanopartículas/química
2.
Carbohydr Polym ; 334: 122009, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38553200

RESUMO

Colon specific delivery of therapeutics have gained much attention of pharmaceutical researchers in the recent past. Colonic specific targeting of drugs is used not only for facilitating absorption of protein or peptide drugs, but also localization of therapeutic agents in colon to treat several colonic disorders. Among various biopolymers, guar gum (GG) exhibits pH dependent swelling, which allows colon specific release of drug. GG also shows microbial degradation in the colonic environment which makes it a suitable excipient for developing colon specific drug delivery systems. The uncontrolled swelling and hydration of GG can be controlled by structural modification or by grafting with another polymeric moiety. Several graft copolymerized guar gum derivatives are investigated for colon targeting of drugs. The efficacy of various guar gum derivatives are evaluated for colon specific delivery of drugs. The reviewed literature evidenced the potentiality of guar gum in localizing drugs in the colonic environment. This review focuses on the synthesis of several guar gum derivatives and their application in developing various colon specific drug delivery systems including matrix tablets, coated formulations, nano or microparticulate delivery systems and hydrogels.


Assuntos
Colo , Sistemas de Liberação de Medicamentos , Colo/metabolismo , Gomas Vegetais/química , Galactanos/química , Mananas/química , Portadores de Fármacos/metabolismo
3.
Biomater Sci ; 12(8): 2007-2018, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38456516

RESUMO

Background: drugs for Alzheimer's disease (AD) fail to exhibit efficacy in clinical trials for a number of reasons, a major one being blood-brain barrier (BBB) permeability. Meanwhile, the increasing incidence of this disease emphasizes the need for effective therapeutics. Herein, we discuss novel nanoplatform technologies developed for the effective delivery of AD drugs by traversing the BBB. Main text: the interfacial and surface chemistry of nanomaterials is utilized in several industries, including pharmaceutical, and has drawn considerable attention in the field of nanotechnology. Various reports have suggested the potential of nanotechnology for AD treatment, describing unique drug carriers that improve drug stability and solubility while maintaining therapeutic dosages. These nanotechnologies are harnessed for the transport of drugs across the BBB, with or without surface modifications. We also discuss the transfer of drugs via the nose-to-brain pathway, as intranasal delivery enables direct drug distribution in the brain. In addition, nanomaterial modifications that prolong drug delivery and improve safety following intranasal administration are addressed. Conclusion: although several studies have yielded promising results, limited efforts have been undertaken to translate research findings into clinical contexts. Nevertheless, nanomaterials hold considerable potential for the development of novel effective therapeutic solutions against AD.


Assuntos
Doença de Alzheimer , Nanopartículas , Humanos , Barreira Hematoencefálica/metabolismo , Administração Intranasal , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/metabolismo , Nanotecnologia
4.
Neuropharmacology ; 249: 109871, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38412889

RESUMO

Dopamine is unable to access the central nervous system through the bloodstream. Only its precursor can do so, and with an effectiveness below 100% of the dose administered, as it is metabolized before crossing the blood-brain barrier. In this study, we describe a new solid lipid nanocarrier system designed and developed for dopamine. The nanoparticles were prepared by the melt-emulsification method and then coated with chitosan. The nanocarriers developed had a droplet size of about 250 nm, a polydispersity index of 0.2, a positive surface charge (+30 mV), and a percentage encapsulation efficiency of 36.3 ± 5.4. Transmission and scanning electron microscopy verified uniformity of particle size with spherical morphology. Various types of tests were performed to confirm that the nanoparticles designed are suitable for carrying dopamine through the blood-brain barrier. In vitro tests demonstrated the ability of these nanocarriers to pass through endothelial cell monolayers without affecting their integrity. This study shows that the formulation of dopamine in chitosan-coated solid lipid nanoparticles is a potentially viable formulation strategy to achieve the bioavailability of the drug for the treatment of Parkinson's disease in the central nervous system.


Assuntos
Quitosana , Lipossomos , Nanopartículas , Portadores de Fármacos/metabolismo , Dopamina/metabolismo , Quitosana/metabolismo , Barreira Hematoencefálica/metabolismo
5.
Adv Drug Deliv Rev ; 207: 115197, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342240

RESUMO

Skin cancer is a heterogeneous disease that can be divided into two main groups, melanoma and nonmelanoma skin cancers. Conventional therapies for skin cancer have numerous systemic side effects and a high recurrence rate. Topical treatment is an alternative approach, but drug permeability remains a challenge. Therefore, nanocarriers appear as important nanotechnology tools that reduces both the side effects and improves clinical outcomes. This is why they are attracting growing interest. In this review, scientific articles on the use of nanocarriers for the topical treatment of skin cancer were collected. Despite the promising results of the presented nanocarriers and considering that some of them are already on the market, there is an urgent need for investment in the development of manufacturing methods, as well as of suitable toxicological and regulatory evaluations, since the conventional methods currently used to develop these nanocarriers-based products are more time-consuming and expensive than conventional products.


Assuntos
Absorção Cutânea , Neoplasias Cutâneas , Humanos , Administração Tópica , Nanotecnologia , Neoplasias Cutâneas/tratamento farmacológico , Portadores de Fármacos/metabolismo , Pele/metabolismo
6.
ACS Biomater Sci Eng ; 10(2): 897-904, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38243792

RESUMO

Particle-cell interactions, such as cellular uptake, vary depending on the particle size, shape, and surface properties. By dynamic control of the physical properties of particles, microparticle-cell interactions can intentionally be altered. Particle degradability is also necessary for their application in the body. In this study, we aimed to prepare degradable core-corona-type particles that are deformed near the body temperature and investigated particle shape-dependent cellular uptake. Degradable and transformable particles consisting of poly(2-methylene-1,3-dioxepane)-co-poly(ethylene glycol) with three-armed poly(ε-caprolactone) (PCL) were prepared. The particle melting point was controlled by the chain length of the three-armed PCL. Particle degradation occurred under both acidic and alkaline conditions via ester group hydrolysis in the polymer backbones. The rod-shaped microparticles prepared by uniaxial stretching at a temperature above the melting point of the core showed less uptake into macrophages than did the spherical microparticles. Therefore, the degradable transformable particles enable macrophage interaction control via stimuli-regulated particle shapes and are expected to be applied as drug delivery carriers that can be decomposed and excreted from the body.


Assuntos
Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/metabolismo , Polímeros/metabolismo , Polietilenoglicóis/farmacologia , Polietilenoglicóis/metabolismo , Macrófagos/metabolismo
7.
J Control Release ; 366: 114-127, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145664

RESUMO

Inflammatory skin diseases represent a significant health concern, affecting approximately 20-25% of the global population. These conditions not only reduce an individual's quality of life but also impose a huge burden on both humanity and society. However, addressing these challenges is hindered by their chronic nature, insufficient therapeutic effectiveness, and the propensity for recurrence and adverse side effects. Hyaluronic acid (HA) has emerged as a potential solution to these barriers, owing to its excellent attributes such as biocompatibility, non-toxicity, and targeted drug delivery. However, its practical application has been limited because endogenous hyaluronidase (HYAL) rapidly degrades HA in inflamed skin thus reducing its ability to penetrate deep into the skin. Interestingly, recent research has expanded the role of self-assembled HA-nanoparticles (HA-NPs) beyond drug carriers; they are resistant to HYAL, thereby enabling deep skin penetration, and possess inherent anti-inflammatory properties. Moreover, these abilities can be fine-tuned depending on the conditions during particle synthesis. Additionally, their role as a drug delivery system holds potential for use as a multi-target drug or hybrid drug. In conclusion, this review aims to specifically introduce and highlight the emerging potential of HA-NPs as a topical treatment for inflammatory skin conditions.


Assuntos
Portadores de Fármacos , Nanopartículas , Portadores de Fármacos/metabolismo , Ácido Hialurônico , Qualidade de Vida , Pele/metabolismo
8.
Drug Deliv ; 30(1): 2288797, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38069500

RESUMO

Nanotechnology has ignited a transformative revolution in disease detection, prevention, management, and treatment. Central to this paradigm shift is the innovative realm of cell membrane-based nanocarriers, a burgeoning class of biomimetic nanoparticles (NPs) that redefine the boundaries of biomedical applications. These remarkable nanocarriers, designed through a top-down approach, harness the intrinsic properties of cell-derived materials as their fundamental building blocks. Through shrouding themselves in natural cell membranes, these nanocarriers extend their circulation longevity and empower themselves to intricately navigate and modulate the multifaceted microenvironments associated with various diseases. This comprehensive review provides a panoramic view of recent breakthroughs in biomimetic nanomaterials, emphasizing their diverse applications in cancer treatment, cardiovascular therapy, viral infections, COVID-19 management, and autoimmune diseases. In this exposition, we deliver a concise yet illuminating overview of the distinctive properties underpinning biomimetic nanomaterials, elucidating their pivotal role in biomedical innovation. We subsequently delve into the exceptional advantages these nanomaterials offer, shedding light on the unique attributes that position them at the forefront of cutting-edge research. Moreover, we briefly explore the intricate synthesis processes employed in creating these biomimetic nanocarriers, shedding light on the methodologies that drive their development.


Assuntos
Nanopartículas , Nanoestruturas , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Nanotecnologia , Membrana Celular/metabolismo
9.
Sci Rep ; 13(1): 22475, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110480

RESUMO

Tumor microenvironment (TME) targeted strategy could control the drug release in tumor cells more accurately and creates a new opportunity for enhanced site-specific targeted delivery. In this study, (PAA-b-PCL-S-S-PCL-b-PAA) copolymeric nanoparticles (NPs) with size-switchable ability and dual pH/redox-triggered drug release behavior were designed to significantly promote cancer uptake (cell internalization of around 100% at 30 min) and site-specific targeted doxorubicin (DOX) delivery in MDA-MB-231 tumor cells. NPs surface charge was shifted from - 17.8 to - 2.4 and their size shrunk from 170.3 to 93 nm in TME. The cell cycle results showed that DOX-loaded NPs showed G2/M (68%) arrest, while free DOX showed sub-G1 arrest (22%). Apoptosis tests confirmed that the cells treated with DOX-loaded NPs showed a higher amount of apoptosis (71.6%) than the free DOX (49.8%). Western blot and RT-PCR assays revealed that the apoptotic genes and protein levels were significantly upregulated using the DOX-loaded NPs vs. the free DOX (Pvalue < 0.001). In conclusion, dual pH/redox-responsive and size-switchable DOX-loaded NPs developed here showed outstanding anti-tumoral features compared with free DOX that might present a prospective platform for tumor site-specific accumulation and drug release that suggest further in vivo research.


Assuntos
Nanopartículas , Neoplasias , Humanos , Microambiente Tumoral , Concentração de Íons de Hidrogênio , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oxirredução , Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos
10.
Biol Pharm Bull ; 46(10): 1353-1364, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779037

RESUMO

Extracellular vesicles (EVs) are a class of nanoparticles that mediate signaling molecules delivery between donor and recipient cells. Heterogeneity in the content of EVs and their membrane surface proteins determines their unique targetability. Their low immunogenicity, capability to cross various biological barriers, and superior biocompatibility enable engineering-modified EVs to be ideal drug delivery carriers. In addition, the engineered EVs that emerge in recent years have become a powerful tool for cancer treatment through the selective delivery of bioactive molecules to therapeutic targets, such as tumor cells and stroma. Our review focuses on the various types of EV modifications and their promoting therapeutic capabilities, which provide an innovative means for cancer precision therapy.


Assuntos
Vesículas Extracelulares , Nanopartículas , Neoplasias , Vesículas Extracelulares/metabolismo , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/metabolismo , Transdução de Sinais , Proteínas de Membrana/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
11.
J Control Release ; 363: 114-135, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37742846

RESUMO

Organelles not only constitute the basic structure of the cell but also are important in maintaining the normal physiological activities of the cell. With the development of biomimetic nanoscience, researchers have developed technologies to use organelles as drug carriers for disease treatment. Compared with traditional drug carriers, organelle drug carriers have the advantages of good biocompatibility, high drug loading efficiency, and modifiability, and the surface biomarkers of organelles can also participate in intracellular signal transduction to enhance intracellular and intercellular communication, and assist in enhancing the therapeutic effect of drugs. Among different types of organelles, extracellular vesicles, lipid droplets, lysosomes, and mitochondria have been used as drug carriers. This review briefly reviews the biogenesis, isolation methods, and drug-loading methods of four types of organelles, and systematically summarizes the research progress in using organelles as drug-delivery systems for disease treatment. Finally, the challenges faced by organelle-based drug delivery systems are discussed. Although the organelle-based drug delivery systems still face challenges before they can achieve clinical translation, they offer a new direction and vision for the development of next-generation drug carriers.


Assuntos
Portadores de Fármacos , Mitocôndrias , Portadores de Fármacos/metabolismo , Mitocôndrias/metabolismo , Lisossomos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Gotículas Lipídicas
12.
J Biomater Sci Polym Ed ; 34(17): 2356-2375, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37622439

RESUMO

A chronic skin disorder called atopic dermatitis (AD) is brought on by the deterioration of the skin's barrier function marked by inflammation, dryness, and bacterial infection along with immunological changes. Althaea officinalis (AO), known for its anti-inflammatory and immunomodulatory properties, has been explored as a potential treatment for AD. This study aimed to develop and evaluate a novel transliposomes (TL) formulation containing AO for AD treatment. Using rotary evaporation, AO-TL formulations were created and optimized employing Box Behnken Design. The optimized AO-TL formulation showed consistent characteristics: vesicle size of 145.8 nm, polydispersity index of 0.201, zeta potential of -28.22 mV, and entrapment efficiency of 86.21%. TEM imaging shows the spherical shapes of the vesicle. These findings demonstrate the formulation's stability and ability to encapsulate AO effectively. In vitro drug release studies revealed that the AO-TL formulation released 81.28% of the drug, outperforming conventional AO dispersion (56.80%). Additionally, when applied to rat skin, the TL gel demonstrated deeper penetration (30 µm) in comparison to the standard solution (5.0 µm) based on confocal laser scanning microscopy (CLSM). Ex vivo and dermatokinetics studies showed improved penetration of drug-loaded transliposomes gel in rat skin than the conventional AO gel. Overall, the optimized AO-TL formulation offers promising characteristics and performance for the topical treatment of AD. Its drug release, antioxidant activity, and deeper penetration suggest enhanced therapeutic effects. Further research and clinical trials are needed to validate its efficacy and safety in AD patients.


Assuntos
Althaea , Dermatite Atópica , Ratos , Humanos , Animais , Absorção Cutânea , Administração Cutânea , Portadores de Fármacos/metabolismo , Dermatite Atópica/tratamento farmacológico , Pele , Tamanho da Partícula
13.
J Nanobiotechnology ; 21(1): 261, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553718

RESUMO

The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.


Assuntos
Depressão , Exossomos , Camundongos , Animais , Nanogéis , Depressão/tratamento farmacológico , Depressão/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Exossomos/metabolismo , Perimenopausa/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Portadores de Fármacos/metabolismo
14.
Adv Mater ; 35(44): e2212000, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37452635

RESUMO

Extracellular vesicles (EVs) are secreted by all living cells and are found in body fluids. They exert numerous physiological and pathological functions and serve as cargo shuttles. Due to their safety and inherent bioactivity, they have emerged as versatile therapeutic agents, biomarkers, and potential drug carriers. Despite the growing interest in EVs, current progress in this field is, in part, limited by relatively inefficient isolation techniques. Conventional methods are indeed slow, laborious, require specialized laboratory equipment, and may result in low yield and purity. This work describes an electrochemically controlled "all-in-one" device enabling capturing, loading, and releasing of EVs. The device is composed of a fluidic channel confined within antibody-coated microstructured electrodes. It rapidly isolates EVs with a high level of purity from various biofluids. As a proof of principle, the device is applied to isolate EVs from skin wounds of healthy and diabetic mice. Strikingly, it is found that EVs from healing wounds of diabetic mice are enriched in mitochondrial proteins compared to those of healthy mice. Additionally, the device improves the loading protocol of EVs with polyplexes, and may therefore find applications in nucleic acid delivery. Overall, the electrochemical device can greatly facilitate the development of EVs-based technologies.


Assuntos
Diabetes Mellitus Experimental , Vesículas Extracelulares , Animais , Camundongos , Diabetes Mellitus Experimental/metabolismo , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo , Comunicação Celular , Portadores de Fármacos/metabolismo
15.
Int J Mol Sci ; 24(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37373342

RESUMO

Exosomes are nanovesicles 40-120 nm in diameter secreted by almost all cell types and providing humoral intercellular interactions. Given the natural origin and high biocompatibility, the potential for loading various anticancer molecules and therapeutic nucleic acids inside, and the surface modification possibility for targeted delivery, exosomes are considered to be a promising means of delivery to cell cultures and experimental animal organisms. Milk is a unique natural source of exosomes available in semi-preparative and preparative quantities. Milk exosomes are highly resistant to the harsh conditions of the gastrointestinal tract. In vitro studies have demonstrated that milk exosomes have an affinity to epithelial cells, are digested by cells by endocytosis mechanism, and can be used for oral delivery. With milk exosome membranes containing hydrophilic and hydrophobic components, exosomes can be loaded with hydrophilic and lipophilic drugs. This review covers a number of scalable protocols for isolating and purifying exosomes from human, cow, and horse milk. Additionally, it considers passive and active methods for drug loading into exosomes, as well as methods for modifying and functionalizing the surface of milk exosomes with specific molecules for more efficient and specific delivery to target cells. In addition, the review considers various approaches to visualize exosomes and determine cellular localization and bio-distribution of loaded drug molecules in tissues. In conclusion, we outline new challenges for studying milk exosomes, a new generation of targeted delivery agents.


Assuntos
Antineoplásicos , Exossomos , Animais , Bovinos , Feminino , Humanos , Exossomos/metabolismo , Leite/metabolismo , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/metabolismo
16.
Adv Drug Deliv Rev ; 200: 114966, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37329985

RESUMO

Gastrointestinal mucus plays essential roles in modulating interactions between intestinal lumen contents, including orally delivered drug carriers and the gut microbiome, and underlying epithelial and immune tissues and cells. This review is focused on the properties of and methods for studying native gastrointestinal mucus and its interactions with intestinal lumen contents, including drug delivery systems, drugs, and bacteria. The properties of gastrointestinal mucus important to consider in its analysis are first presented, followed by a discussion of different experimental setups used to study gastrointestinal mucus. Applications of native intestinal mucus are then described, including experimental methods used to study mucus as a barrier to drug delivery and interactions with intestinal lumen contents that impact barrier properties. Given the significance of the microbiota in health and disease, its impact on drug delivery and drug metabolism, and the use of probiotics and microbe-based delivery systems, analysis of interactions of bacteria with native intestinal mucus is then reviewed. Specifically, bacteria adhesion to, motility within, and degradation of mucus is discussed. Literature noted is focused largely on applications of native intestinal mucus models as opposed to isolated mucins or reconstituted mucin gels.


Assuntos
Aderência Bacteriana , Portadores de Fármacos , Humanos , Portadores de Fármacos/metabolismo , Intestinos , Mucinas/metabolismo , Muco/metabolismo , Bactérias/metabolismo , Mucosa Intestinal/metabolismo
17.
Environ Res ; 233: 116454, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37343751

RESUMO

Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.


Assuntos
Canabidiol , Nanoestruturas , Neoplasias Cutâneas , Humanos , Absorção Cutânea , Canabidiol/metabolismo , Canabidiol/farmacologia , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Pele , Fluoruracila/metabolismo , Fluoruracila/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Lipídeos , Tamanho da Partícula
18.
Chem Phys Lipids ; 255: 105315, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37356610

RESUMO

Drug delivery through the skin improves solubility, bioavailability, and unwanted systemic side effects of the drug. The selection of a suitable carrier is a challenging process. The conventional lipid vesicles have some limitations. They deliver the drug in the stratum corneum and have poor colloidal stability. Here comes the need for ultra-deformable lipid vesicles to provide the drug beyond the stratum corneum. Transethosomes are novel ultra-deformable vesicles that can deliver drugs into deeper tissues. The composition of transethosomes includes phospholipid, ethanol and surfactants. Each ingredient has a pivotal role in the properties of the carrier. This review covers the design, preparation method, characterisation, and characteristics of the novel vesicle. Also, we cover the impact of surfactants on vesicular properties and the skin permeation behaviour of novel vesicles.


Assuntos
Absorção Cutânea , Pele , Administração Cutânea , Pele/metabolismo , Sistemas de Liberação de Medicamentos , Fosfolipídeos/metabolismo , Etanol , Tensoativos/farmacologia , Portadores de Fármacos/metabolismo , Lipossomos/metabolismo
19.
Eur J Pharm Sci ; 186: 106458, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37137418

RESUMO

The present study screened the utility of topically-applied nanoformulations to target the drugs/actives into the skin reservoir with the reduction of possible systemic absorption. The lipid-based nanoformulations selected in this study included solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions (NEs), liposomes, and niosomes. We loaded flavanone and retinoic acid (RA) as the penetrants. The prepared nanoformulations were assessed for their average diameter, polydispersity index (PDI), and zeta potential. An in vitro permeation test (IVPT) was utilized to determine the skin delivery into/across pig skin, atopic dermatitis (AD)-like mouse skin, and photoaged mouse skin. We found an increased skin absorption of lipid nanoparticles following the increase of solid lipid percentage in the formulations (SLNs > NLCs > NEs). The use of liposomes even reduced the dermal/transdermal selectivity (S value) to lessen the cutaneous targeting. The niosomes resulted in significantly greater RA deposition and reduced permeation in the Franz cell receptor compared to the other nanoformulations. The S value of the RA delivery via stripped skin was increased by 26-fold in the niosomes compared to the free RA. The dye-labeled niosomes displayed a strong fluorescence in the epidermis and upper dermis through the visualization of fluorescence and confocal microscopies. The cyanoacrylate skin biopsy manifested greater hair follicle uptake of the niosomes compared to the free penetrants by 1.5 to three-fold. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay indicated an increase in antioxidant ability from 55% to 75% after flavanone entrapment in the niosomes. In the activated keratinocytes, the niosomal flavanone could suppress the overexpressed CCL5 to the baseline control because of the facile cell internalization. After the formulation optimization, the niosomes with higher phospholipid amount had a superior effect in delivering penetrants into the skin reservoir, with limited permeation to the receptors.


Assuntos
Lipossomos , Absorção Cutânea , Camundongos , Animais , Suínos , Lipossomos/metabolismo , Pele/metabolismo , Administração Cutânea , Tretinoína , Lipídeos , Portadores de Fármacos/metabolismo
20.
Biomolecules ; 13(5)2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37238708

RESUMO

Plant cells release tiny membranous vesicles called extracellular vesicles (EVs), which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. These plant-derived EVs (PDEVs) are safe and easily extractable and have been shown to have therapeutic effects against inflammation, cancer, bacteria, and aging. They have shown promise in preventing or treating colitis, cancer, alcoholic liver disease, and even COVID-19. PDEVs can also be used as natural carriers for small-molecule drugs and nucleic acids through various administration routes such as oral, transdermal, or injection. The unique advantages of PDEVs make them highly competitive in clinical applications and preventive healthcare products in the future. This review covers the latest methods for isolating and characterizing PDEVs, their applications in disease prevention and treatment, and their potential as a new drug carrier, with special attention to their commercial viability and toxicological profile, as the future of nanomedicine therapeutics. This review champions the formation of a new task force specializing in PDEVs to address a global need for rigor and standardization in PDEV research.


Assuntos
COVID-19 , Vesículas Extracelulares , Neoplasias , Humanos , COVID-19/metabolismo , Vesículas Extracelulares/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/metabolismo , Neoplasias/metabolismo
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