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1.
Expert Opin Drug Deliv ; : 1-22, 2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39397403

RESUMO

INTRODUCTION: Alzheimer's disease (AD) stands as significant challenge in realm of neurodegenerative disorder. It is characterized by gradual decline in cognitive function and memory loss. It has already expanded its prevalence to 55 million people worldwide and is expected to rise significantly. Unfortunately, there exists a limited therapeutic option that would mitigate its progression. Repurposing existing drugs and employing nanoparticle as delivery agent presents a potential solution to address the intricate pathology of AD. AREAS COVERED: In this review, we delve into utilization of nanoparticular platforms to enhance the delivery of repurposed drugs for treatment of AD. Firstly, the review begins with the elucidation of intricate pathology underpinning AD, subsequently followed by rationale behind drug repurposing in AD. Covered are explorations of nanoparticle-based repurposing of drugs in AD, highlighting their clinical implication. Further, the associated challenges and probable future perspective are delineated. EXPERT OPINION: The article has highlighted that extensive research has been carried out on the delivery of repurposed nanomedicines against AD. However, there is a need for advanced and long-term research including clinical trials required to shed light upon their safety and toxicity profile. Furthermore, their scalability in pharmaceutical set-up should also be validated.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39126576

RESUMO

Nanoparticulate drug delivery systems (NDDS) based nanoformulations have emerged as promising drug delivery systems. Various NDDS-based formulations have been reported such as polymeric nanoparticles (NPs), nanoliposomes, solid lipid NPs, nanocapsules, liposomes, self-nano emulsifying drug delivery systems, pro liposomes, nanospheres, microemulsion, nanoemulsion, gold NPs, silver NPs and nanostructured lipid carrier. They have shown numerous advantages such as enhanced bioavailability, aqueous solubility, permeability, controlled release profile, and blood-brain barrier (BBB) permeability. This advantage of NDDS can help to deliver pure drugs to the target site. However, the formulation of nanoparticles is a complex process that requires optimization to ensure product quality and efficacy. Quality by Design (QbD) is a systemic approach that has been implemented in the pharmaceutical industry to improve the quality and reliability of drug products. QbD involves the optimization of different parameters like zeta potential (ZP), particle size (PS), entrapment efficiency (EE), polydispersity index (PDI), and drug release using statistical experimental design. The present article discussed the detailed role of QbD in optimizing nanoformulations and their advantages, advancement, and applications from the industrial perspective. Various case studies of QbD in the optimization of nanoformulations are also discussed.

3.
Pathol Res Pract ; 261: 155490, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39126977

RESUMO

Pyroptosis is an inflammatory programed cell death process that plays a crucial role in cancer therapeutic, while Gasdermin-D is a critical effector protein for pyroptosis execution. This review discusses the intricate interactions between Gasdermin-D and some non-coding RNAs (lncRNA, miRNA, siRNA) and their potential application in the regulation of pyroptosis as an anticancer therapy. Correspondingly, these ncRNAs significantly implicate in Gasdermin-D expression and function regarding the pyroptosis pathway. Functioning as competing endogenous RNAs (ceRNAs), these ncRNAs might regulate Gasdermin-D at the molecular level, underlying fatal cell death caused by cancer and tumor propagation. Therefore, these interactions appeal to therapeutics, offering new avenues for cancer treatment. It address this research gap by discussing the possible roles of ncRNAs as mediators of gasdermin-D regulation. It suggest therapeutic strategies based on the current research findings to ensure the interchange between the ideal pyroptosis and cancer cell death.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias , Proteínas de Ligação a Fosfato , Piroptose , RNA não Traduzido , Piroptose/fisiologia , Humanos , Neoplasias/patologia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Animais , Regulação Neoplásica da Expressão Gênica , Gasderminas
4.
Life Sci ; 352: 122859, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38925223

RESUMO

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.


Assuntos
Antineoplásicos , Proliferação de Células , Reposicionamento de Medicamentos , Neoplasias Pulmonares , Ribavirina , Humanos , Reposicionamento de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Ribavirina/farmacologia , Células A549 , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Simulação de Acoplamento Molecular , Antivirais/farmacologia , Biologia Computacional/métodos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo
5.
Drug Deliv Transl Res ; 14(10): 1-17, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38789909

RESUMO

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.


Assuntos
Disponibilidade Biológica , Colo , Emulsões , Flavonoides , Flavonóis , Galactanos , Pectinas , Polissacarídeos Bacterianos , Flavonóis/farmacocinética , Flavonóis/administração & dosagem , Flavonóis/química , Animais , Colo/metabolismo , Flavonoides/farmacocinética , Flavonoides/administração & dosagem , Flavonoides/química , Masculino , Administração Oral , Galactanos/química , Galactanos/farmacocinética , Galactanos/administração & dosagem , Pectinas/química , Pectinas/farmacocinética , Pectinas/administração & dosagem , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacocinética , Polissacarídeos Bacterianos/administração & dosagem , Gomas Vegetais/química , Gomas Vegetais/farmacocinética , Gomas Vegetais/administração & dosagem , Mananas/química , Mananas/farmacocinética , Mananas/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Nanopartículas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Liberação Controlada de Fármacos , Solubilidade
6.
Drug Deliv Transl Res ; 14(9): 2325-2344, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38758498

RESUMO

Skin cancer remains one of the most prominent types of cancer. Melanoma and non-melanoma skin cancer are commonly found together, with melanoma being the more deadly type. Skin cancer can be effectively treated with chemotherapy, which mostly uses small molecular medicines, phytoceuticals, and biomacromolecules. Topical delivery of these therapeutics is a non-invasive way that might be useful in effectively managing skin cancer. Different skin barriers, however, presented a major obstacle to topical cargo administration. Transferosomes have demonstrated significant potential in topical delivery by improving cargo penetration through the circumvention of diverse skin barriers. Additionally, the transferosome-based gel can prolong the residence of drug on the skin, lowering the frequency of doses and their associated side effects. However, the choice of appropriate transferosome compositions, such as phospholipids and edge activators, and fabrication technique are crucial for achieving improved entrapment efficiency, penetration, and regulated particle size. The present review discusses skin cancer overview, current treatment strategies for skin cancer and their drawbacks. Topical drug delivery against skin cancer is also covered, along with the difficulties associated with it and the importance of transferosomes in avoiding these difficulties. Additionally, a summary of transferosome compositions and fabrication methods is provided. Furthermore, topical delivery of small molecular drugs, phytoceuticals, and biomacromolecules using transferosomes and transferosomes-based gel in treating skin cancer is discussed. Thus, transferosomes can be a significant option in the topical delivery of drugs to manage skin cancer efficiently.


Assuntos
Antineoplásicos , Lipossomos , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Animais , Administração Cutânea , Sistemas de Liberação de Medicamentos , Absorção Cutânea
7.
Ageing Res Rev ; 98: 102322, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723753

RESUMO

Age-related macular degeneration (AMD) is a significant factor contributing to serious vision loss in adults above 50. The presence of posterior segment barriers serves as chief roadblocks in the delivery of drugs to treat AMD. The conventional treatment strategies use is limited due to its off-targeted distribution in the eye, shorter drug residence, poor penetration and bioavailability, fatal side effects, etc. The above-mentioned downside necessitates drug delivery using some cutting-edge technology including diverse nanoparticulate systems and microneedles (MNs) which provide the best therapeutic delivery alternative to treat AMD efficiently. Furthermore, cutting-edge treatment modalities including gene therapy and stem cell therapy can control AMD effectively by reducing the boundaries of conventional therapies with a single dose. This review discusses AMD overview, conventional therapies for AMD and their restrictions, repurposed therapeutics and their anti-AMD activity through different mechanisms, and diverse barriers in drug delivery for AMD. Various nanoparticulate-based approaches including polymeric NPs, lipidic NPs, exosomes, active targeted NPs, stimuli-sensitive NPs, cell membrane-coated NPs, inorganic NPs, and MNs are explained. Gene therapy, stem cell therapy, and therapies in clinical trials to treat AMD are also discussed. Further, bottlenecks of cutting-edge (nanoparticulate) technology-based drug delivery are briefed. In a nutshell, cutting-edge technology-based therapies can be an effective way to treat AMD.


Assuntos
Terapia Genética , Degeneração Macular , Humanos , Degeneração Macular/terapia , Terapia Genética/métodos , Terapia Genética/tendências , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , Animais , Nanopartículas/uso terapêutico , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/tendências
8.
Int J Pharm ; 660: 124172, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38679243

RESUMO

The goal of this study was to formulate tacrolimus nanogel based on nanostructured lipid carrier (NLC) in order to improve the efficacy, aesthetic, and patient compliance for the treatment of psoriasis. The microemulsion method was used to create phase diagrams and NLCs were prepared using points obtained from the microemulsion region and characterized. The gelling agent carbopol was used to develop an NLC-based nanogel. The pH, drug assay, viscosity, spreadability, and in vitro release of the nanogel, were evaluated. Ex vivo cytotoxicity of the formulation was assessed in murine fibroblast cells. Oxazolone and imiquimod models of psoriasis were used to assess the effectiveness of the nanogel. The NLCs exhibited a submicron particle size of 320 ± 10 nm, a low polydispersity index (<0.3), and a zeta potential of -19.4 mV. Morphological analysis revealed spherical nanoparticles with an encapsulation efficiency of 60 ± 3 %. The nanogel maintained a pH of 6.0 ± 0.5 and possessed a remarkable drug content of 99.73 ± 1.4 %. It exhibited pseudoplastic flow behaviour, ensuring easy spreadability, and demonstrated sustained drug release exceeding 90 % over a 24-hr period. Ex vivo cytotoxicity assessments revealed that the nanogel was safe because no cell death was induced. Nanogel resolved psoriatic blisters, was non-irritating and improved skin elasticity. The favorable properties, safety profile, and remarkable efficacy show the potential of the nanogel as a patient-friendly and effective therapeutic option for psoriasis treatment.


Assuntos
Portadores de Fármacos , Liberação Controlada de Fármacos , Lipídeos , Nanogéis , Psoríase , Tacrolimo , Psoríase/tratamento farmacológico , Animais , Portadores de Fármacos/química , Camundongos , Lipídeos/química , Lipídeos/administração & dosagem , Tacrolimo/administração & dosagem , Tacrolimo/química , Tacrolimo/farmacocinética , Nanogéis/química , Preparações de Ação Retardada , Tamanho da Partícula , Nanoestruturas/química , Nanoestruturas/administração & dosagem , Nanopartículas/química , Imunossupressores/administração & dosagem , Imunossupressores/química , Masculino , Imiquimode/administração & dosagem , Fibroblastos/efeitos dos fármacos , Química Farmacêutica/métodos , Géis , Polietilenoglicóis/química , Polietilenoglicóis/administração & dosagem , Polietilenoimina
9.
Pathol Res Pract ; 255: 155157, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38320440

RESUMO

Lung cancer (LCs) is still a serious health problem globally, with many incidences attributed to environmental triggers such as Volatile Organic Compounds (VOCs). VOCs are a broad class of compounds that can be released via various sources, including industrial operations, automobile emissions, and indoor air pollution. VOC exposure has been linked to an elevated risk of lung cancer via multiple routes. These chemicals can be chemically converted into hazardous intermediate molecules, resulting in DNA damage and genetic alterations. VOCs can also cause oxidative stress, inflammation, and a breakdown in the cellular protective antioxidant framework, all of which contribute to the growth of lung cancer. Moreover, VOCs have been reported to alter critical biological reactions such as cell growth, apoptosis, and angiogenesis, leading to tumor development and metastasis. Epidemiological investigations have found a link between certain VOCs and a higher probability of LCs. Benzene, formaldehyde, and polycyclic aromatic hydrocarbons (PAHs) are some of the most well-researched VOCs, with comprehensive data confirming their cancer-causing potential. Nevertheless, the possible health concerns linked with many more VOCs and their combined use remain unknown, necessitating further research. Identifying the toxicological consequences of VOCs in LCs is critical for establishing focused preventative tactics and therapeutic strategies. Better legislation and monitoring mechanisms can limit VOC contamination in occupational and environmental contexts, possibly reducing the prevalence of LCs. Developing VOC exposure indicators and analyzing their associations with genetic susceptibility characteristics may also aid in early identification and targeted therapies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Neoplasias Pulmonares , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/efeitos adversos , Compostos Orgânicos Voláteis/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise
10.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 751-762, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37650889

RESUMO

The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.


Assuntos
Antiasmáticos , Asma , Microbiota , Humanos , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/metabolismo , Pulmão/metabolismo , Bactérias
11.
Artigo em Inglês | MEDLINE | ID: mdl-37991539

RESUMO

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for both ailments. These diseases share common pathogenetic mechanisms including inflammation, oxidative stress, and tissue remodelling. Current therapeutic approaches are limited by low efficacy and adverse effects. Consequentially, LC has a 5-year survival of < 20%, while COPD is incurable, underlining the necessity for innovative treatment strategies. Two promising emerging classes of therapy against these diseases include plant-derived molecules (phytoceuticals) and nucleic acid-based therapies. The clinical application of both is limited by issues including poor solubility, poor permeability, and, in the case of nucleic acids, susceptibility to enzymatic degradation, large size, and electrostatic charge density. Nanoparticle-based advanced drug delivery systems are currently being explored as flexible systems allowing to overcome these limitations. In this review, an updated summary of the most recent studies using nanoparticle-based advanced drug delivery systems to improve the delivery of nucleic acids and phytoceuticals for the treatment of LC and COPD is provided. This review highlights the enormous relevance of these delivery systems as tools that are set to facilitate the clinical application of novel categories of therapeutics with poor pharmacokinetic properties. This picture was generated with BioRender.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38036849

RESUMO

In recent year, the research of transdermal drug delivery systems has got substantial attention towards the development of microneedles (MNs). This shift has occurred due to multifaceted advantages of MNs as they can be utilized to deliver the drug deeper to the skin with minimal invasion, offer successful delivery of drugs and biomolecules that are susceptible to degradation in gastrointestinal tract (GIT), act as biosensors, and help in monitoring the level of biomarkers in the body. These can be fabricated into different types based on their applications as well as material for fabrication. Some of their types include solid MNs, hollow MNs, coated MNs, hydrogel forming MNs, and dissolving MNs. These MNs deliver the therapeutics via microchannels deeper into the skin. The coated and hollow MNs have been found successful. However, they suffer from poor drug loading and blocking of pores. In contrast, dissolving MNs offer high drug loading. These MNs have also been utilized to deliver vaccines and biologicals. They have also been used in cosmetics. The current review covers the different types of MNs, materials used in their fabrication, properties of MNs, and various case studies related to their role in delivering therapeutics, monitoring level of biomarkers/hormones in body such as insulin. Various patents and clinical trials related to MNs are also covered. Covered are the major bottlenecks associated with their clinical translation and potential future perspectives.

13.
AAPS PharmSciTech ; 24(5): 106, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37085596

RESUMO

Simvastatin (SMV) is noticed as a repurposed candidate to be effective against breast cancer (BC). However, poor solubility, dose-limiting toxicities, and side effects are critical hurdles in its use against BC. The above drawbacks necessitate the site-specific (localized) delivery of SMV via suitable nanocarriers. Therefore, the present study intended to develop SMV nanostructured lipid carrier (NLC)-based gel using carbopol-934 as a gelling agent to achieve local delivery and improve patient compliance while combating BC. The SMV NLCs were fabricated by melt-emulsification ultrasonication technique using stearic acid as solid lipid, olive oil (OO) as liquid lipid, tween 20 as a surfactant, and PEG-200 as a co-surfactant, and optimized by Box-Behnken design. The optimized SMV-loaded NLCs displayed % entrapment efficiency of 91.66 ± 5.2% and particle size of 182 ± 11.9 nm. The pH of NLC-based gels prepared using a 2.0% w/v of carbopol-934 was found in the range of 5.3-5.6 while the viscosity was in the range of 5.1-6.6 Pa.S. Besides, NLC-based gels exhibited higher and controlled SMV release (71-76%) at pH 6.8 and (78-84%) at pH 5.5 after 48 h than SMV conventional gel (37%) at both pH 6.8 and 5.5 after 48 h. The ex vivo permeation of SMV from NLC-based gel was 3.8 to 4.5 times more than conventional gel. Notably, SMV-loaded NLCs displayed ameliorated cytotoxicity than plain SMV against MCF-7 and MDA-MB-231 BC cells. No substantial difference was noticed in the cytotoxicity of NLC-based gels and pure SMV against both cell lines. The SMV NLC-based gel exhibited the absence of skin irritation in vivo in the mice following topical application. In addition, the histopathological study revealed no alteration in the mice skin anatomy. Furthermore, the SMV-loaded NLCs and NLC-based gels were stable for 6 months at refrigerator conditions (4°C ± 2°C). Thus, the present research confirms that NLC-based gel can be a safe, efficacious, and novel alternative to treat BC.


Assuntos
Nanoestruturas , Neoplasias , Camundongos , Animais , Portadores de Fármacos/química , Nanoestruturas/química , Géis/química , Excipientes , Tensoativos , Lipídeos/química , Tamanho da Partícula
14.
J Control Release ; 353: 1150-1170, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36566843

RESUMO

Cancer ranks as the second foremost cause of death in various corners of the globe. The clinical uses of assorted anticancer therapeutics have been limited owing to the poor physicochemical attributes, pharmacokinetic performance, and lethal toxicities. Various sorts of co-crystals or nano co-crystals or co-crystals-laden nanocarriers have presented great promise in targeting cancer via improved physicochemical attributes, pharmacokinetic performance, and reduced toxicities. These systems have also demonstrated the controlled cargo release and passive targeting via enhanced permeation and retention (EPR) effect. In addition, regional delivery of co-crystals via inhalation and transdermal route displayed remarkable potential in targeting lung and skin cancer effectively. However, more research is required on the use of co-crystals in cancer and their commercialization. The present review mainly emphasizes co-crystals as emerging avenues in the treatment of various cancers by modulating the physicochemical and pharmacokinetic attributes of approved anticancer therapeutics. The worth of co-crystals in cancer treatment, computational paths in the co-crystals screening, diverse experimental techniques of co-crystals fabrication, and sorts of co-crystals and their noteworthy applications in targeting cancer are also discussed. Besides, the game changer approaches like nano co-crystals and co-crystals-laden nanocarriers, and co-crystals in regional delivery in cancer are also explained with reported case studies. Furthermore, regulatory directives for pharmaceutical co-crystals and their scale-up, and challenges are also highlighted with concluding remarks and future initiatives. In essence, co-crystals and nano co-crystals emerge to be a promising strategy in overwhelming cancers through improving anticancer efficacy, safety, patient compliance, and reducing the cost.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias Cutâneas , Humanos , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos
15.
Braz. J. Pharm. Sci. (Online) ; 59: e21820, 2023. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1439542

RESUMO

ABSTRACT Diabetes is a life-threatening disease, and currently available synthetic medicines for treating diabetes are associated with various side effects. Therefore, there is an unmet need to develop herbal remedies against diabetes as an alternative to synthetic medicines. Although local healers use the roots of Spermadicyton suaveolens (SS) to manage diabetes, there is negligible research to validate its antidiabetic properties. The present investigation aims to the assess the antioxidant, antidiabetic, and antihyperlipidemic potential of the ethanolic extract of S. Suaveolen's roots (EESS) on streptozotocin (STZ) induced diabetic rats. The extract was screened for in vitro antioxidant and antidiabetic activity. The in vivo antidiabetic potential of EESS (at 200 and 400 mg/kg) was studied on STZ-induced diabetic rats for 20 days. The EESS displayed significant (p<0.05) antidiabetic and antioxidant properties. The administration of 200 mg/kg and 400 mg/kg EESS in STZ-induced diabetic rats significantly reduced hyperglycemia, and restored antioxidant enzymes and lipid profile-a high density lipoprotein (HDL) increased by the administration of a single dose of streptozotocin. Thus, EESS could be a promising herbal medicine in the treatment of diabetes and hyperlipidemia


Assuntos
Animais , Masculino , Ratos , Extratos Vegetais/análise , Estreptozocina/efeitos adversos , Diabetes Mellitus Experimental/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Antioxidantes/farmacologia , Técnicas In Vitro/métodos , Medicina Herbária/classificação , Medicamento Fitoterápico , Medicamentos Sintéticos/efeitos adversos , Hiperlipidemias/complicações
16.
Chem Biol Interact ; 368: 110238, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306865

RESUMO

Polysaccharides (PS) represent a broad class of polymer-based compounds that have been extensively researched as therapeutics and excipients for drug delivery. As pharmaceutical carriers, PS have mostly found their use as adsorbents, suspending agents, as well as cross-linking agents for various formulations such as liposomes, nanoparticles, nanoemulsions, nano lipid carriers, microspheres etc. This is due to inherent properties of PS such as porosity, steric stability and swellability, insolubility in pH. There have been emerging reports on the use of PS as therapeutic agent due to its anti-inflammatory and anti-oxidative properties for various diseases. In particular, for Crohn's disease, ulcerative colitis and inflammatory bowel disease. However, determining the dosage, treatment duration and effective technology transfer of these therapeutic moieties have not occurred. This is due to the fact that PS are still at a nascent stage of development to a full proof therapy for a particular disease. Recently, a combination of polysaccharide which act as a prebiotic and a probiotic have been used as a combination to treat various intestinal and colorectal (CRC) related diseases. This has proven to be beneficial, has shown good in vivo correlation and is well reported. The present review entails a detailed description on the role of PS used as a therapeutic agent and as a formulation pertaining to gastrointestinal diseases.


Assuntos
Colite Ulcerativa , Polímeros , Humanos , Sistemas de Liberação de Medicamentos , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Preparações Farmacêuticas , Portadores de Fármacos/química
17.
J Control Release ; 349: 812-830, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35914614

RESUMO

Breast cancer (BC) is a highly diagnosed and topmost cause of death in females worldwide. Drug repurposing (DR) has shown great potential against BC by overcoming major shortcomings of approved anticancer therapeutics. However, poor physicochemical properties, pharmacokinetic performance, stability, non-selectivity to tumors, and side effects are severe hurdles in repurposed drug delivery against BC. The variety of nanocarriers (NCs) has shown great promise in delivering repurposed therapeutics for effective treatment of BC via improving solubility, stability, tumor selectivity and reducing toxicity. Besides, delivering repurposed cargos via theranostic NCs can be helpful in the quick diagnosis and treatment of BC. Localized delivery of repurposed candidates through apt NCs can diminish the systemic side effects and improve anti-tumor effectiveness. However, breast tumor variability and tumor microenvironment have created several challenges to nanoparticulate delivery of repurposed cargos. This review focuses on DR as an ingenious strategy to treat BC and circumvent the drawbacks of approved anticancer therapeutics. Various nanoparticulate avenues delivering repurposed therapeutics, including non-oncology cargos and vaccines to target BC effectively, are discussed along with case studies. Moreover, clinical trial information on repurposed medications and vaccines for the treatment of BC is covered along with various obstacles in nanoparticulate drug delivery against cancer that have been so far identified. In a nutshell, DR and drug delivery of repurposed drugs via NCs appears to be a propitious approach in devastating BC.


Assuntos
Neoplasias da Mama , Vacinas , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Reposicionamento de Medicamentos , Feminino , Humanos , Preparações Farmacêuticas , Microambiente Tumoral , Vacinas/uso terapêutico
18.
Eur J Pharmacol ; 926: 175031, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35580707

RESUMO

Skin cancer is one of the most common forms of cancer. Several million people are estimated to have affected with this condition worldwide. Skin cancer generally includes melanoma and non-melanoma with the former being the most dangerous. Chemotherapy has been one of the key therapeutic strategies employed in the treatment of skin cancer, especially in advanced stages of the disease. It could be also used as an adjuvant with other treatment modalities depending on the type of skin cancer. However, there are several shortfalls associated with the use of chemotherapy such as non-selectivity, tumour resistance, life-threatening toxicities, and the exorbitant cost of medicines. Furthermore, new drug discovery is a lengthy and costly process with minimal likelihood of success. Thus, drug repurposing (DR) has emerged as a new avenue where the drug approved formerly for the treatment of one disease can be used for the treatment of another disease like cancer. This approach is greatly beneficial over the de novo approach in terms of time and cost. Moreover, there is minimal risk of failure of repurposed therapeutics in clinical trials. There are a considerable number of studies that have reported on drugs repurposed for the treatment of skin cancer. Thus, the present manuscript offers a comprehensive overview of drugs that have been investigated as repurposing candidates for the efficient treatment of skin cancers mainly melanoma and its oncogenic subtypes, and non-melanoma. The prospects of repurposing phytochemicals against skin cancer are also discussed. Furthermore, repurposed drug delivery via topical route and repurposed drugs in clinical trials are briefed. Based on the findings from the reported studies discussed in this manuscript, drug repurposing emerges to be a promising approach and thus is expected to offer efficient treatment at a reasonable cost in devitalizing skin cancer.


Assuntos
Melanoma , Neoplasias Cutâneas , Descoberta de Drogas , Reposicionamento de Medicamentos , Humanos , Melanoma/tratamento farmacológico , Preparações Farmacêuticas , Neoplasias Cutâneas/tratamento farmacológico , Melanoma Maligno Cutâneo
19.
Int J Pharm ; 618: 121681, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35307469

RESUMO

Nanotechnology has been a dynamic field for formulation scientists with multidisciplinary research being conducted worldwide. Advancements in development of functional nanosystems have led to evolution of breakthrough technologies. Lipidic nanosystems, in particular, are highly preferred owing to their non-immunogenic safety profiles along with a range of versatile intrinsic properties. Surface modification of lipid nanoparticles by anchoring carbohydrates to these systems is one such attractive drug delivery technology. Carbohydrates confer interesting properties to the nanosystems such as stealth, biostability, bioavailability, reduced toxicity due to decreased immunogenic response, targeting potential as well as ease of commercial availability. The carbohydrate anchored systems can be developed using methods such as adsorption, incorporation (nanoprecipitation or solvent displacement method), crosslinking and grafting. Current review provides a detailed overview of potential lipid based nanoparticulate systems with an emphasis on liposomes, solid lipid nanoparticles, nanostructures lipid carriers and micelles. Review further explores basics of surface modification, methods applied therein, advantages of carbohydrates as surface modifiers, their versatile applications, techniques for characterization of carbohydrate anchored systems and vital regulatory aspects concerned with these specialized systems.


Assuntos
Lipossomos , Nanopartículas , Carboidratos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanopartículas/química
20.
Drug Discov Today ; 27(5): 1495-1512, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35158056

RESUMO

Polymeric micelles (PMs) have been explored pre-clinically for the delivery of chemotherapeutics to treat cancer. Their unique features, such as easy surface functionalization, stimuli-responsiveness, good stability, ability to modify drug release, enhanced permeation and retention effect, and potential to encapsulate more than one type of therapeutic molecules at a time, make them unique carriers for the targeted delivery or for enhancing the bioavailability of chemotherapeutics. PMs can also be used as theranostic nanocarriers for the mapping of drug therapy along with tumor imaging in patients with cancer. This review focuses on the limitations of existing treatment strategies and on innovative approaches employed for the functionalization of PMs for targeting cancer cells. In addition, the bottlenecks associated with the translation of PMs from the laboratory to clinics are also discussed.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Micelas , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Polímeros/uso terapêutico
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