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1.
Artículo en Inglés | MEDLINE | ID: mdl-38995610

RESUMEN

Abiraterone acetate (ABA), a biopharmaceutical class IV drug suffers from solubility and permeability pitfalls resulting in limited oral bioavailability and positive food effect, i.e. multi-fold enhancement in drug absorption in the presence of food. This poses difficulties to physicians towards the estimation of dose and dosage regimen required for efficacious therapy of prostate cancer (PCa). Nanostructured lipid carriers (NLC) have demonstrated tremendous outcomes in enhancing the oral bioavailability of various entities along with food effect attenuation. In this study, Quality by design and multivariate analysis was employed for optimization of ABA loaded NLC (ABA NLC). The optimal size, PDI and zeta potential obtained using QbD were 134.6 nm, 0.163 and -15.7 mV respectively. Ex vivo qualitative and quantitative intestinal permeability studies demonstrated improved traversion of NLC through the intestinal segments. In vitro dissolution profile in biorelevant fast and fed gastric and intestinal media revealed minimal differences for ABA NLC compared to ABA. In vivo pharmacokinetics was performed to decipher the efficacy of ABA NLC in mitigating the food effect of ABA. The studies demonstrated 14.51-fold and 1.94-fold improvement in oral bioavailability during fasted and fed state respectively as compared to free ABA. The absorption mechanism of ABA NLC using chylomicron flow blocking approach conveyed lymphatic uptake as the major mechanism. Cmax fast/fed ratio was 0.9758 whereas, AUC fast/fed ratio was 0.9386, which being nearly equivalent, confirmed the food effect attenuation. Therefore, the results of the study demonstrate optimal pharmacokinetics of ABA NLC and its utility in circumventing the fast fed variability.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39009931

RESUMEN

Breast cancer (BC) is the most commonly diagnosed cancer among women. Chemo-, immune- and photothermal therapies are employed to manage BC. However, the tumor microenvironment (TME) prevents free drugs and nanocarriers (NCs) from entering the tumor premises. Formulation scientists rely on enhanced permeation and retention (EPR) to extravasate NCs in the TME. However, recent research has demonstrated the inconsistent nature of EPR among different patients and tumor types. In addition, angiogenesis, high intra-tumor fluid pressure, desmoplasia, and high cell and extracellular matrix density resist the accumulation of NCs in the TME. In this review, we discuss TME normalization as an approach to improve the penetration of drugs and NCSs in the tumor premises. Strategies such as normalization of tumor vessels, reversal of hypoxia, alleviation of high intra-tumor pressure, and infiltration of lymphocytes for the reversal of therapy failure have been discussed in this manuscript. Strategies to promote the infiltration of anticancer immune cells in the TME after vascular normalization have been discussed. Studies strategizing time points to administer TME-normalizing agents are highlighted. Mechanistic pathways controlling the angiogenesis and normalization processes are discussed along with the studies. This review will provide greater tumor-targeting insights to the formulation scientists.

3.
Int J Nanomedicine ; 19: 5397-5418, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863647

RESUMEN

Background: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries. Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair. Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31±0.09 mm and 12±0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10. Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.


Asunto(s)
Ampicilina , Quemaduras , Colágeno , Escherichia coli , Nanofibras , Alcohol Polivinílico , Povidona , Resveratrol , Staphylococcus aureus , Cicatrización de Heridas , Resveratrol/farmacología , Resveratrol/química , Resveratrol/administración & dosificación , Resveratrol/farmacocinética , Nanofibras/química , Quemaduras/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Colágeno/química , Povidona/química , Staphylococcus aureus/efectos de los fármacos , Alcohol Polivinílico/química , Humanos , Escherichia coli/efectos de los fármacos , Ampicilina/farmacología , Ampicilina/química , Ampicilina/farmacocinética , Ampicilina/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Ratas , Biopelículas/efectos de los fármacos , Masculino
4.
Curr Drug Targets ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38910425

RESUMEN

Mitochondria are an essential intracellular organelle for medication targeting and delivery since they seem to create energy and conduct many other cellular tasks, and mitochondrial dysfunctions and malfunctions lead to many illnesses. Many initiatives have been taken to detect, diagnose, and image mitochondrial abnormalities, and to transport and accumulate medicines precisely to mitochondria, all because of special mitochondrial aspects of the pathophysiology of cancer. In addition to the negative membrane potential and paradoxical mitochondrial dynamics, they include high temperatures, high levels of reactive oxygen species, high levels of glutathione, and high temperatures. Neurodegenerative diseases represent a broad spectrum of debilitating illnesses. They are linked to the loss of certain groups of neurons based on an individual's physiology or anatomy. The mitochondria in a cell are generally accepted as the authority with respect to ATP production. Disruption of this system is linked to several cellular physiological issues. The development of neurodegenerative disorders has been linked to mitochondrial malfunction, according to pathophysiological studies. There seems to be substantial evidence connecting mitochondrial dysfunction and oxidative stress to the development of neurodegenerative disorders. It has been extensively observed that mitochondrial malfunction triggers autophagy, which plays a role in neurodegenerative disorders. In addition, excitotoxicity and mitochondrial dysfunction have been linked to the development of neurodegenerative disorders. The pathophysiology of neurodegenerative illnesses has been linked to increased apoptosis and necrosis, as well as mitochondrial malfunction. A variety of synthetic and natural treatments have shown efficacy in treating neurodegenerative illnesses caused by mitochondrial failure. Neurodegenerative illnesses can be effectively treated with existing drugs that target mitochondria, although their precise formulations are poorly understood. Therefore, there is an immediate need to focus on creating drug delivery methods specifically targeted at mitochondria in the treatment and diagnosis of neurodegenerative disorders.

5.
Curr Pharm Des ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38859792

RESUMEN

Organ-on-chip is an innovative technique that emerged from tissue engineering and microfluidic technologies. Organ-on-chip devices (OoCs) are anticipated to provide efficient resolutions to dealing with challenges in pharmaceutical advancement and individualized illness therapies. Organ-on-chip is an advanced method that can replicate human organs' physiological conditions and functions on a small chip. It possesses the capacity to greatly transform the drug development process by enabling the simulation of diseases and the testing of drugs. Effective integration of this advanced technical platform with common pharmaceutical and medical contexts is still a challenge. Microfluidic technology, a micro-level technique, has become a potent tool for biomedical engineering research. As a result, it has revolutionized disciplines including physiological material interpreting, compound detection, cell-based assay, tissue engineering, biological diagnostics, and pharmaceutical identification. This article aims to offer an overview of newly developed organ-on-a-chip systems. It includes single-organ platforms, emphasizing the most researched organs, including the heart, liver, blood arteries, and lungs. Subsequently, it provides a concise overview of tumour-on-a-chip systems and emphasizes their use in the evaluation of anti-cancer medications.

6.
Radiat Prot Dosimetry ; 200(10): 881-889, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38834189

RESUMEN

This research forms a part of the comprehensive Indian Environmental Radiation Monitoring Network program, focusing on the continuous measurement of absorbed dose rate in outdoor air due to natural gamma radiation (cosmic and terrestrial) in Bengaluru, Karnataka, India. Over the course of a decade (2013-2023), data were collected from 41 monitoring locations in the city using permanently field-installed Geiger-Mueller detector-based environmental radiation monitors. This paper presents an analysis of the extensive long-term monitoring results. The mean absorbed gamma dose rate in outdoor air across the monitoring locations ranged from 84 ± 9 to 156 ± 4 nGy.h-1, with a calculated mean value of 124 ± 15 nGy.h-1. The estimated mean annual effective dose due to outdoor natural gamma radiation varied from 0.10 ± 0.01 to 0.19 ± 0.01 mSv.y-1, with an overall mean of 0.15 ± 0.02 mSv.y-1.


Asunto(s)
Contaminantes Radiactivos del Aire , Radiación de Fondo , Rayos gamma , Dosis de Radiación , Monitoreo de Radiación , India , Monitoreo de Radiación/métodos , Contaminantes Radiactivos del Aire/análisis , Humanos
7.
Eur J Pharm Biopharm ; 201: 114361, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38871092

RESUMEN

Chimeric Antigen Receptor-T cell (CAR-T) therapy has evolved as a revolutionary cancer treatment modality, offering remarkable clinical responses by harnessing the power of a patient's immune system to target and eliminate cancer cells. However, the development and commercialization of CAR-T cell therapies are accompanied by complex regulatory requirements and challenges. This therapy falls under the regulatory category of advanced therapy medicinal products. The regulatory framework and approval tools of regenerative medicine, especially CAR-T cell therapies, vary globally. The present work comprehensively analyses the regulatory landscape and challenges in CAR-T cell therapy development in four key regions: the United States, the European Union, Japan, and India. This work explores the unique requirements and considerations for preclinical studies, clinical trial design, manufacturing standards, safety evaluation, and post-marketing surveillance in each jurisdiction. Due to their complex nature, developers and manufacturers face several challenges. In India, despite advancements in treatment protocols and government-sponsorships, there are still several difficulties regarding access to treatment for the increasing number of cancer patients. However, India's first indigenously developed CAR-T cell therapy, NexCAR19, for B-cell lymphoma or leukemia, approved and available at a low cost compared to other available CAR-T therapies, raises great hope in the battle against cancer. Several strategies are proposed to address the identified hurdles from global and Indian perspectives. It discusses the benefits of aligning regulatory requirements across regions, eventually facilitating international development and enabling access to this transformative therapy.


Asunto(s)
Unión Europea , Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Humanos , India , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/legislación & jurisprudencia , Estados Unidos , Japón , Receptores Quiméricos de Antígenos/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Vigilancia de Productos Comercializados/métodos , Ensayos Clínicos como Asunto/métodos
8.
Ther Deliv ; : 1-8, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38888757

RESUMEN

Ophthalmic diseases can result in permanent vision loss and blindness. Convenient topical and systemic treatments are preferred to address these sight-threatening conditions. However, the unique anatomy of the eye presents challenges for drug delivery. Various ophthalmic ointment formulations have been developed to enhance bioavailability in the eye to prolong residence time and improve corneal permeability. This article explores a wide range of ocular diseases affecting individuals globally and how ointments are used to manage them. From eye to ocular barriers, this review focuses on published scientific research and formulation strategies for severe ocular complications using conventional topical ointments. Additionally, it delves through patented technologies and marketed formulations supporting the use of ointments in ocular drug delivery.


Eye illnesses can cause blindness. The treatment is tricky due to eye's complex makeup. This paper talks about eye ointments also known as 'creams' or 'pomades' used to deliver medicine to the eye. These creams make the medicine work better by staying in the eye longer and absorbing faster. The present work looks at different eye problems and talks about ointments used to treat both internal and external eye diseases. It also explains how the eye is built and why it is hard for medicine to get in. There is also an information about ointments that have been discovered with some new ideas and those available in the market to cure eye problems.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38696091

RESUMEN

The current advent explores the potential of itraconazole (ITR) in prostate cancer (PCa), by its incorporation into albumin nanoparticles (NP). ITR as a repurposed moiety has displayed tremendous potential in various cancers. However, poor aqueous solubility poses hurdles towards its clinical translation. Amorphisation of ITR was observed post-incorporation within NP matrix which could prevent its precipitation in aqueous media. ITR NP was developed using quality by design and multivariate analysis and evaluated for cellular uptake, cell proliferation inhibition and the mechanism of PCa cell inhibition. Time and concentration-dependent serum stability and hemolytic potential revealed safety of ITR NP. Morphological changes and nuclear staining studies revealed the efficacy of ITR and ITR NP in promoting growth inhibition of PC-3 cells. Superior qualitative and quantitative uptake, reactive oxygen species (ROS) and mitochondrial impairment for ITR NP in comparison with ITR and control group was observed. Cell cycle study revealed remarkable G2/M phase inhibition in PC-3 cells. ITR NP demonstrated superior anticancer potential in 3D tumoroids mimicking the micro-metastatic lesions compared to control and ITR. Hence, ITR NP can be a favorable alternative therapeutic alternative in PCa.

10.
Mol Pharm ; 21(5): 2118-2147, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38660711

RESUMEN

The various kinds of nanocarriers (NCs) have been explored for the delivery of therapeutics designed for the management of skin manifestations. The NCs are considered as one of the promising approaches for the skin delivery of therapeutics attributable to sustained release and enhanced skin penetration. Despite the extensive applications of the NCs, the challenges in their delivery via skin barrier (majorly stratum corneum) have persisted. To overcome all the challenges associated with the delivery of NCs, the microneedle (MN) technology has emerged as a beacon of hope. Programmable drug release, being painless, and its minimally invasive nature make it an intriguing strategy to circumvent the multiple challenges associated with the various drug delivery systems. The integration of positive traits of NCs and MNs boosts therapeutic effectiveness by evading stratum corneum, facilitating the delivery of NCs through the skin and enhancing their targeted delivery. This review discusses the barrier function of skin, the importance of MNs, the types of MNs, and the superiority of NC-loaded MNs. We highlighted the applications of NC-integrated MNs for the management of various skin ailments, combinational drug delivery, active targeting, in vivo imaging, and as theranostics. The clinical trials, patent portfolio, and marketed products of drug/NC-integrated MNs are covered. Finally, regulatory hurdles toward benchtop-to-bedside translation, along with promising prospects needed to scale up NC-integrated MN technology, have been deliberated. The current review is anticipated to deliver thoughtful visions to researchers, clinicians, and formulation scientists for the successful development of the MN-technology-based product by carefully optimizing all the formulation variables.


Asunto(s)
Administración Cutánea , Sistemas de Liberación de Medicamentos , Agujas , Enfermedades de la Piel , Piel , Humanos , Sistemas de Liberación de Medicamentos/métodos , Enfermedades de la Piel/tratamiento farmacológico , Piel/metabolismo , Piel/efectos de los fármacos , Nanopartículas/química , Nanopartículas/administración & dosificación , Portadores de Fármacos/química , Animales , Absorción Cutánea , Microinyecciones/métodos , Microinyecciones/instrumentación
12.
Artículo en Inglés | MEDLINE | ID: mdl-38509343

RESUMEN

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180-230 nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel.

13.
Life Sci ; 343: 122545, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38458556

RESUMEN

Type-1 Diabetes Mellitus (T1DM) manifests due to pancreatic beta cell destruction, causing insulin deficiency and hyperglycaemia. Current therapies are inadequate for brittle diabetics, necessitating pancreatic islet transplants, which however, introduces its own set of challenges such as paucity of donors, rigorous immunosuppression and autoimmune rejection. Organoid technology represents a significant stride in the field of regenerative medicine and bypasses donor-based approaches. Hence this article focuses on strategies enhancing the in vivo engraftment of islet organoids (IOs), namely vascularization, encapsulation, immune evasion, alternative extra-hepatic transplant sites and 3D bioprinting. Hypoxia-induced necrosis and delayed revascularization attenuate organoid viability and functional capacity, alleviated by the integration of diverse cell types e.g., human amniotic epithelial cells (hAECs) and human umbilical vein endothelial cells (HUVECs) to boost vascularization. Encapsulation with biocompatible materials and genetic modifications counters immune damage, while extra-hepatic sites avoid surgical complications and immediate blood-mediated inflammatory reactions (IBMIR). Customizable 3D bioprinting may help augment the viability and functionality of IOs. While the clinical translation of IOs faces hurdles, preliminary results show promise. This article underscores the importance of addressing challenges in IO transplantation to advance their use in treating type 1 diabetes effectively.


Asunto(s)
Diabetes Mellitus Tipo 1 , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Humanos , Trasplante de Islotes Pancreáticos/métodos , Diabetes Mellitus Tipo 1/cirugía , Organoides , Células Endoteliales de la Vena Umbilical Humana
14.
Curr Drug Targets ; 25(4): 278-300, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38409709

RESUMEN

Compared to the conventional approach, nanoparticles (NPs) facilitate a non-hazardous, non-toxic, non-interactive, and biocompatible system, rendering them incredibly promising for improving drug delivery to target cells. When that comes to accomplishing specific therapeutic agents like drugs, peptides, nucleotides, etc., lipidic nanoparticulate systems have emerged as even more robust. They have asserted impressive ability in bypassing physiological and cellular barriers, evading lysosomal capture and the proton sponge effect, optimizing bioavailability, and compliance, lowering doses, and boosting therapeutic efficacy. However, the lack of selectivity at the cellular level hinders its ability to accomplish its potential to the fullest. The inclusion of surface functionalization to the lipidic NPs might certainly assist them in adapting to the basic biological demands of a specific pathological condition. Several ligands, including peptides, enzymes, polymers, saccharides, antibodies, etc., can be functionalized onto the surface of lipidic NPs to achieve cellular selectivity and avoid bioactivity challenges. This review provides a comprehensive outline for functionalizing lipid-based NPs systems in prominence over target selectivity. Emphasis has been put upon the strategies for reinforcing the therapeutic performance of lipidic nano carriers' using a variety of ligands alongside instances of relevant commercial formulations.


Asunto(s)
Sistemas de Liberación de Medicamentos , Lípidos , Nanopartículas , Humanos , Nanopartículas/química , Lípidos/química , Portadores de Fármacos/química , Animales , Liposomas
15.
Colloids Surf B Biointerfaces ; 234: 113732, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38181691

RESUMEN

Cabazitaxel has been approved for the treatment of prostate cancer since 2010. However, its poor solubility and permeability pitfalls prevent its accumulation at the target site and promote severe adverse effects. About 90% of prostate cancer (PCa) patients suffer from bone metastasis. This advent reports the development of CBZ-loaded pH-responsive polydopamine nanoparticles (CBZ NP) against metastatic PCa cells. Quality by design (QbD) and multivariate analysis tools were employed for the optimization of CBZ NP. Amorphisation of CBZ along with metastatic microenvironment responsive release was observed thereby imparting spatial release and circumventing solubility pitfalls. CBZ NP retained its cytotoxic potential, with a significant increase in quantitative cellular uptake. Apoptotic markers observed from nuclear staining with elevated reactive oxygen species (ROS) and mitochondrial damage revealed by JC-1 staining demonstrated the efficacy of CBZ NP against PC-3 cells with good serum stability and diminished hemolysis. Cell cycle analysis revealed substantial S and G2/M phase arrest with enhancement in apoptosis was observed. Western blot studies revealed an elevation in caspase-1 and suppression in Bcl-2 indicating enhanced apoptosis compared to the control group. Substantial reduction in the diameter of 3D-Tumoroid and enhanced cell proliferation inhibition indicated the efficacy of CBZ NP in PCa. Thus, we conclude that CBZ NP could be a promising Nanotherapeutic approach for PCa.


Asunto(s)
Antineoplásicos , Neoplasias de la Próstata , Taxoides , Humanos , Masculino , Línea Celular Tumoral , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Concentración de Iones de Hidrógeno , Microambiente Tumoral
16.
Drug Deliv Transl Res ; 14(5): 1218-1231, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37903963

RESUMEN

Bosutinib (BOS) is a BCS class IV drug that shows low oral bioavailability and high fast-fed variability. Various pharmaceutical formulations have been explored thus far in order to improve its bioavailability while avoiding fast-fed variability. In the present study, we explored cyclodextrin (CD) complexation strategy to overcome the aforementioned disadvantages associated with BOS. CD complexation is a simple, versatile and economic approach that enables formation of inclusion complexes, thereby improving aqueous solubility while nullifying pH-dependent solubility and fast-fed variability for poorly soluble drugs. Initially, we performed molecular dynamics and docking studies to select appropriate CD derivative. The results of in silico studies revealed that sulfo-butyl ether ß-cyclodextrin (SBE-CD) offered superior binding affinity with BOS. Further, Job's plot revealed that 1:1 stoichiometry of BOS and CD resulted in enhancement of BOS solubility up to ~ 132.6-folds. In vitro release studies in bio-relevant media (fasted and fed state simulated gastric and intestinal fluids) revealed higher drug release while overcoming its pH-dependent solubility. In vitro studies on K562 cells demonstrated a 1.83-fold enhancement in cytotoxicity due to enhanced ROS production and G2/M phase arrest.In vivo pharmacokinetic studies in Sprague-Dawley rats revealed insignificant fast-fed variability with AUCfast/fed 0.9493 and Cmaxfast/fed 0.8291 being closer to 1 in comparison with BOS. Hence, we conclude that SBE-CD complexation could be a promising approach in diminishing fast-fed variability of BOS.


Asunto(s)
Compuestos de Anilina , Ciclodextrinas , Nitrilos , Quinolinas , beta-Ciclodextrinas , Ratas , Animales , Ratas Sprague-Dawley , beta-Ciclodextrinas/química , Ciclodextrinas/química , Solubilidad , Éteres
17.
J Microencapsul ; 41(1): 27-44, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37982590

RESUMEN

AIM: Our aim was to repurpose atorvastatin for melanoma by encapsulating in a nanostructured lipid carrier matrix to promote tumour cell internalisation and skin permeation. pH-responsive chitosan gel was employed to restrict At-NLCs in upper dermal layers. METHODS: We utilised a quality by design approach for encapsulating At within the NLC matrix. Further, cellular uptake and cytotoxicity was evaluated along with pH-responsive release and ex vivo skin permeation. RESULTS: Cytotoxicity assay showed 3.13-fold enhanced cytotoxicity on melanoma cells compared to plain drug with nuclear staining showing apoptotic markers. In vitro, release studies showed 5.9-fold rapid release in chitosan gel matrix at pH 5.5 compared to neutral pH. CONCLUSIONS: At-NLCs prevented precipitation, promoted skin permeation, and SK-MEL 28 cell internalisation. The localisation of NLCs on the upper dermal layer due to electrostatic interactions of skin with chitosan gel diminished the incidence of untoward systemic effects.


Asunto(s)
Quitosano , Melanoma , Nanoestructuras , Humanos , Portadores de Fármacos/farmacología , Atorvastatina/farmacología , Melanoma/tratamiento farmacológico , Quitosano/farmacología , Piel , Tamaño de la Partícula
18.
Int J Biol Macromol ; 256(Pt 2): 128452, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38042321

RESUMEN

Cancer is a devastating disease that causes a substantial number of deaths worldwide. Current therapeutic interventions for cancer include chemotherapy, radiation therapy, or surgery. These conventional therapeutic approaches are associated with disadvantages such as multidrug resistance, destruction of healthy tissues, and tissue toxicity. Therefore, there is a paradigm shift in cancer management wherein nanomedicine-based novel therapeutic interventions are being explored to overcome the aforementioned disadvantages. Supramolecular self-assembled peptide nanofibers are emerging drug delivery vehicles that have gained much attention in cancer management owing to their biocompatibility, biodegradability, biomimetic property, stimuli-responsiveness, transformability, and inherent therapeutic property. Supramolecules form well-organized structures via non-covalent linkages, the intricate molecular arrangement helps to improve tissue permeation, pharmacokinetic profile and chemical stability of therapeutic agents while enabling targeted delivery and allowing efficient tumor imaging. In this review, we present fundamental aspects of peptide-based self-assembled nanofiber fabrication their applications in monotherapy/combinatorial chemo- and/or immuno-therapy to overcome multi-drug resistance. The role of self-assembled structures in targeted/stimuli-responsive (pH, enzyme and photo-responsive) drug delivery has been discussed along with the case studies. Further, recent advancements in peptide nanofibers in cancer diagnosis, imaging, gene therapy, and immune therapy along with regulatory obstacles towards clinical translation have been deliberated.


Asunto(s)
Nanofibras , Neoplasias , Humanos , Nanofibras/química , Péptidos/química , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Inmunidad Celular
19.
Nanomedicine (Lond) ; 18(26): 1941-1959, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37991203

RESUMEN

Aim: This work aims to synthesize the gold nanoparticles (GNPs) using a dual extract of tulsi and Vinca (T+V-Gold) for breast cancer tumor regression. Methods: The GNPs were synthesized and characterized for their microscopic, spectroscopic and crystalline properties. Further, the GNPs were investigated for in vitro and in vivo studies for the treatment of the 4T1-induced triple-negative breast cancer murine model. Results: The GNPs for 4T1 tumor-challenged mice resulted in delayed tumor development and lower tumor burden, with T+V-Gold demonstrating the highest prevention of tumor spread. The antitumor effect of T+V-Gold is highly significant in the glutathione family antioxidants glutathione S-transferase and glutathione in tumor tissue samples. Conclusion: The bioefficacy and anticancer outcomes of T+V-Gold nanoformulation can be used as therapeutic agents and drug-delivery vehicles.


Asunto(s)
Nanopartículas del Metal , Neoplasias , Vinca , Ratones , Animales , Oro/química , Nanopartículas del Metal/química , Glutatión/química
20.
Pharm Dev Technol ; 28(10): 1056-1078, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38018532

RESUMEN

Transethosomes, classified as 3rd generation nanocarriers, have gained global acclaim due to their profound potential in addressing diverse medical conditions. Their superior dermal penetration, attributed to essential constituents, such as edge activators and alcohol, sets them apart from other nanoformulations. The current review article embarks with an introduction followed by a comprehensive exploration of transethosome structures, differentiating them from fellow nanocarriers. A detailed analysis of characteristics and the spectrum of marketed products of various nanocarriers is also provided. Furthermore, the article offers a taxonomy of preparation methods of transethosomes and reports the frequently employed methods. It briefly surveys research studies encompassing various drug categories, spanning a wide range of medical conditions. In summary, this review article is dedicated to achieving several pivotal aims and objectives. We aim to substantiate the superior attributes of transethosomes when compared to conventional commercial products and other nanoformulations, demonstrating their clinical promise in addressing various human medical conditions. Additionally, we seek to elucidate the regulatory pathway required to secure approvals for transethosomes from relevant regulatory authorities and shine a light on their innovative potential as revealed in patent literature. Collectively, these objectives contribute to a comprehensive understanding of the significance and potential of transethosomes in the field of pharmaceutical nanotechnology.


Asunto(s)
Etanol , Absorción Cutánea , Humanos , Sistemas de Liberación de Medicamentos/métodos
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