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1.
Pharm Dev Technol ; 29(5): 492-503, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38682603

RESUMO

Bedaquiline fumarate (BQF) is classified as a BCS class II drug and has poor water solubility and dissolution rate, which ultimately compromises bioavailability. The objective of this study is to improve the biopharmaceutical properties of BQF through a solid dispersion system by using Soluplus®. Two solid dispersion systems were prepared i.e. binary solid dispersion (BSD) and ternary solid dispersion (TSD) where 14.31-fold and 20.43-fold increase in solubility of BQF was observed with BSD and TSD in comparison to BQF. In our previous research work, we explored the BSD and TSD of BQF with a crystalline polymer, poloxamer 188, which showed an increment in the solubility of BQF. In the current research, amorphous Soluplus® polymer was selected to formulate BSD and TSD with BQF and showed higher solubility than poloxamer 188. The various solid and liquid state characterization results confirmed the presence of an amorphous form of BQF inside solid dispersion. The Fourier transform infrared spectroscopy showed no chemical interactions between BQF and polymer. The cellular uptake results demonstrated higher uptake in Caco-2 cell lines. Pharmacokinetic studies showed enhanced solubility and bioavailability of TSDs. Hence, the present research shows a promising formulation strategy for enhancing the biopharmaceutical performance of BQF by increasing its solubility.


Assuntos
Disponibilidade Biológica , Diarilquinolinas , Polietilenoglicóis , Polivinil , Solubilidade , Polivinil/química , Células CACO-2 , Humanos , Animais , Diarilquinolinas/farmacocinética , Diarilquinolinas/química , Diarilquinolinas/farmacologia , Polietilenoglicóis/química , Masculino , Ratos , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Antituberculosos/farmacocinética , Antituberculosos/química , Antituberculosos/farmacologia , Antituberculosos/administração & dosagem , Poloxâmero/química
2.
AAPS PharmSciTech ; 24(8): 226, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37945925

RESUMO

Amphotericin B (AmB) is a membrane-acting antibiotic used for the treatment of fungal and protozoal infections. AmB exists in various molecular forms, i.e., monomeric, super-aggregated, and oligomeric forms, where oligomeric forms are highly toxic because of their relative affinity toward cholesterol present over human cell membrane. Hence, the objective of our research work was to study the aggregation state of AmB in two different nanoformulations, i.e., solid lipid nanoparticles (SLNs) and zein-based nanoparticles (PNPs), with the aim of enhancing the fraction of less toxic form of AmB, and a comparative study was performed. The zein and glyceryl monostearate can intercalate the polyenic domain of AmB and thereby hinder the hydrophobic attractions between the AmB molecules, which allows their existence in monomeric forms. The particle size of AmB-SLNs and AmB-PNPs were 378.90 ± 9.50 nm and 184.90 ± 6.00 nm, while zeta potential was -34.97 ± 0.51 mV and +28.93 ± 2.29 mV, respectively. In vitro release studies showed more controlled release of AmB from PNPs (52.48 ± 1.07%) as compared to SLNs (86.33 ± 0.93%). The predominant aggregation state of AmB in both formulations was determined by UV-visible and circular dichroism spectrophotometry, where a higher degree of monomerization of AmB was reported in AmB-SLNs as compared to AmB-PNPs. Toxicity of the nanoformulations was evaluated through hemolysis test, where the results suggested that AmB-SLNs and AmB-PNPs were less hemolytic as compared to pure AmB. The nanoformulations demonstrated the predominant monomeric form of AmB, which may offer higher selectivity index toward microbial membrane.


Assuntos
Nanopartículas , Zeína , Humanos , Anfotericina B/química , Antifúngicos/química , Nanopartículas/química , Polímeros
3.
Chem Res Toxicol ; 35(10): 1701-1719, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-35972774

RESUMO

Arsenic, a metalloid, is known to cause deleterious effects in various body organs, particularly the liver, urinary bladder, and brain, and these effects are primarily mediated through oxidative stress. Chelation therapy has been considered one of the promising medical treatments for arsenic poisoning. Meso 2,3- dimercaptosuccinic acid (DMSA) has been recognized as one of the most effective chelating drugs to treat arsenic poisoning. However, the drug is compromised with a number of shortcomings, including the inability to treat chronic arsenic poisoning due to its extracellular distribution. Monoisoamyl 2,3-dimercaptosuccinic acid, one of the analogues of meso 2,3-dimeraptosuccinic acid (DMSA), is a lipophilic chelator and has shown promise to be considered as a potential future chelating agent/antidote not only for arsenic but also for a few other heavy metals like lead, mercury, cadmium, and gallium arsenide. The results from numerous studies carried out in the recent past, mainly from our group, strongly support the clinical application of MiADMSA. This review paper summarizes most of the scientific details including the chemistry, pharmacology, and safety profile of MiADMSA. The efficacy of MiADMSA mainly against arsenic toxicity but also a few other heavy metals was also discussed. We also reviewed a few other strategies in order to achieve the optimum effects of MiADMSA, like combination therapy using two chelating agents or coadministration of a natural and synthetic antioxidant (including phytomedicine) along with MiADMSA for treatment of metal/metalloid poisoning. We also briefly discussed the use of nanotechnology (nano form of MiADMSA i.e. nano-MiADMSA) and compared it with bulk MiADMSA. All these strategies have been shown to be beneficial in getting more pronounced therapeutic efficacy of MiADMSA, as an adjuvant or as a complementary agent, by significantly increasing the chelating efficacy of MiADMSA.


Assuntos
Intoxicação por Arsênico , Arsênio , Mercúrio , Animais , Antídotos , Antioxidantes/uso terapêutico , Intoxicação por Arsênico/tratamento farmacológico , Cádmio , Quelantes/farmacologia , Quelantes/uso terapêutico , Intoxicação por Metais Pesados/tratamento farmacológico , Ratos , Ratos Wistar , Succímero/análogos & derivados , Succímero/farmacologia , Succímero/uso terapêutico
4.
AAPS PharmSciTech ; 23(5): 125, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474400

RESUMO

The accumulation of amyloid-beta at the neuronal sites is a major pathological hallmark involved in the etiology of Alzheimer's disease. To reduce the Aß-induced neuronal cytotoxicity, selenium nanoparticles and silymarin were fabricated in a single polysaccharide matrix for dual antioxidant and Aß fibril disaggregation activity. These nanoparticles were further stabilized by an exopolysaccharide xanthan gum. The nanoparticles were fabricated to reduce the amyloid-induced cytotoxicity in SH-SY5Y cells. A three-step method employing redox reaction of sodium selenite and ascorbic acid has been adopted for the synthesis of selenium nanoparticles. Consequently, xanthan gum powder was added to impart stability to the nanocarriers. The nanoparticles exhibited a particle size of 119.2 ± 2.8 nm, zeta potential of - 35.4 ± 3.8 mV, and % EE of 87.7 ± 2.23. HR-TEM with EDX analysis confirmed the presence of spherical nanoparticles. An in vitro drug release study exhibited 89.33 ± 5.4% release of silymarin from nanocarriers and was able to scavenge 90% free radicals of DPPH reagent. The thioflavin T (ThT) fibrillation kinetics study showed that the nanoparticles elicited maximum disaggregation of Aß fibrils that was depicted by the quenched fluorescence intensity signal. The cell viability results revealed that the highest neuroprotection activity was observed in the cell group treated with SLY-XG-Se against Aß 1-42-induced toxicity. The nanoparticles were able to internalize in SH-SY5Y cells. Our findings showed that the nanocarrier elicited anti-aggregation efficacy in neuronal cell lines and mitigated the Aß-induced cytotoxicity, which represents the prospects of neuroprotection involved in the therapeutics of AD.


Assuntos
Selênio , Silimarina , Amiloide , Peptídeos beta-Amiloides/metabolismo , Polissacarídeos Bacterianos , Silimarina/farmacologia
5.
Molecules ; 26(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806788

RESUMO

Clean and safe water is a fundamental human need for multi-faceted development of society and a thriving economy. Brisk rises in populations, expanding industrialization, urbanization and extensive agriculture practices have resulted in the generation of wastewater which have not only made the water dirty or polluted, but also deadly. Millions of people die every year due to diseases communicated through consumption of water contaminated by deleterious pathogens. Although various methods for wastewater treatment have been explored in the last few decades but their use is restrained by many limitations including use of chemicals, formation of disinfection by-products (DBPs), time consumption and expensiveness. Nanotechnology, manipulation of matter at a molecular or an atomic level to craft new structures, devices and systems having superior electronic, optical, magnetic, conductive and mechanical properties, is emerging as a promising technology, which has demonstrated remarkable feats in various fields including wastewater treatment. Nanomaterials encompass a high surface to volume ratio, a high sensitivity and reactivity, a high adsorption capacity, and ease of functionalization which makes them suitable for application in wastewater treatment. In this article we have reviewed the techniques being developed for wastewater treatment using nanotechnology based on adsorption and biosorption, nanofiltration, photocatalysis, disinfection and sensing technology. Furthermore, this review also highlights the fate of the nanomaterials in wastewater treatment as well as risks associated with their use.

6.
Antimicrob Agents Chemother ; 59(5): 2479-87, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25645852

RESUMO

The present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0 G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR), (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0 G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency, in vitro drug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellular Leishmania donovani amastigotes, in vivo pharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagic L. donovani amastigotes. In the in vitro cell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs. In vivo studies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.


Assuntos
Anfotericina B/metabolismo , Nanoconjugados/química , Anfotericina B/química , Animais , Antiprotozoários/metabolismo , Antiprotozoários/farmacologia , Linhagem Celular , Sistemas de Liberação de Medicamentos/normas , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/metabolismo , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Polipropilenos/química
7.
Nanomedicine ; 11(3): 705-13, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25596078

RESUMO

This paper describes a novel strategy for targeted delivery of amphotericin B (AmB) to macrophages with muramyl dipeptide (MDP) conjugated multimeric poly(propyleneimine) (PPI) dendrimers. Synergistic antiparasitic activity due to immunostimulation by multimeric presentation of MDP on dendrimers was anticipated. MDP conjugated 5.0G PPI (MdPPI) dendrimers were synthesized and characterized. Therapeutic activity and toxicity of dendrimeric formulation of AmB (MdPPIA) were compared with marketed formulations of AmB. Highly significant (P<0.01) reduction in toxicity was observed in hemolytic toxicity and cytotoxicity studies in erythrocytes and J774A.1 macrophage cells, respectively. Formulation MdPPIA showed appreciable macrophage targeting potential and higher or equivalent antiparasitic activity against parasite infected macrophage cell lines and in vivo infection in Balb/c mice. These results suggest the developed MDP conjugated dendrimeric formulation of AmB as a promising immunostimulant targeted drug delivery system and a safer alternative to marketed formulations. From the clinical editor: Parasitic infections remain a significant issue in the clinical setting. The authors in this article studied the use of ligand anchored dendrimeric formulation of Amphotericin B to target infected macrophages and showed reduced toxicity, high anti-leishmanial activity. This may add another treatment option to available formulations in the future.


Assuntos
Acetilmuramil-Alanil-Isoglutamina/farmacologia , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Dendrímeros/farmacologia , Portadores de Fármacos/farmacologia , Polipropilenos/farmacologia , Acetilmuramil-Alanil-Isoglutamina/efeitos adversos , Acetilmuramil-Alanil-Isoglutamina/química , Anfotericina B/efeitos adversos , Anfotericina B/química , Animais , Antifúngicos/efeitos adversos , Antifúngicos/química , Dendrímeros/efeitos adversos , Dendrímeros/química , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/química , Avaliação Pré-Clínica de Medicamentos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Polipropilenos/efeitos adversos , Polipropilenos/química
8.
Nanomedicine (Lond) ; 19(5): 367-382, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305304

RESUMO

Aim: The present research focused on development and optimization of ligand decorated theranostic nanocarrier encapsulating paclitaxel and carbon quantum dots (CQDs). Methods: CQDs were prepared by microwave-assisted pyrolysis and were characterized for particle size and fluorescence behavior. Ligand decorated zein nanoparticles, coloaded with paclitaxel and CQDs, were formulated using a one-step nanoprecipitation method and optimized for various process parameters. Results: Particle size for coated and uncoated nanoparticles was 90.16 ± 1.65 and 179.26 ± 3.61 nm, respectively, and entrapment efficiency was >80%. The circular dichroism spectroscopy showed zein retained its secondary structure and release study showed biphasic release behavior. Conclusion: The prepared theranostic nanocarrier showed optimal fluorescence and desired release behavior without altering the secondary structure of zein.


Assuntos
Nanopartículas , Pontos Quânticos , Zeína , Pontos Quânticos/química , Paclitaxel/química , Zeína/química , Medicina de Precisão , Carbono/química , Ligantes , Nanopartículas/química
9.
Expert Opin Drug Deliv ; 21(8): 1235-1250, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39161976

RESUMO

INTRODUCTION: Development of novel vascular networks is a fundamental requirement for tumor growth and progression. In the last decade, biomarkers and underlying molecular pathways of angiogenesis have been intensely investigated to disrupt the initiation and progression of tumor angiogenesis. However, the clinical applications of anti-angiogenic agents are constrained due to toxic side effects, acquired drug resistance, and unavailability of validated biomarkers. AREA COVERED: This review discusses the development of dendrimeric nanocarriers that could be a promising domain to explore for the eradication of current challenges associated with angiogenesis-based cancer therapy. Novel drug-delivery approaches with subtle readouts and better understanding of molecular mechanisms have revealed that dendrimers comprise innate anti-angiogenic activity and incorporation of anti-angiogenic agents or gene-silencing RNA could lead to synergistic anti-angiogenic and anticancer effects with reduced side effects. EXPERT OPINION: Dendrimer-mediated targeting of angiogenic biomarkers has efficiently led to the vascular normalization, and rational linking of dendrimers with anti-angiogenic agent or siRNA or both might be a potential area to eradicate the current challenges of angiogenesis-based cancer therapy. However, drawbacks associated with the dendrimers-mediated targeting of angiogenic biomarkers, such as poor stability or small expression of these biomarkers on the normal cells, limit their application at market scale.


Assuntos
Inibidores da Angiogênese , Biomarcadores Tumorais , Dendrímeros , Sistemas de Liberação de Medicamentos , Neoplasias , Neovascularização Patológica , Dendrímeros/química , Humanos , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Biomarcadores Tumorais/metabolismo , Portadores de Fármacos/química , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Nanopartículas
10.
Expert Opin Drug Deliv ; 21(2): 187-210, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38243810

RESUMO

INTRODUCTION: Amphotericin B (AmB), a promising antifungal and antileishmanial drug, acts on the membrane of microorganisms. The clinical use of AmB is limited due to issues associated with its delivery including poor solubility and bioavailability, instability in acidic media, poor intestinal permeability, dose and aggregation state dependent toxicity, parenteral administration, and requirement of cold chain for transport and storage, etc. AREAS COVERED: Scientists have formulated and explored various covalent conjugates of AmB to reduce its toxicity with increase in solubility, oral bioavailability, and payload or loading of AmB by using various polymers, lipids, carbon-based nanocarriers, metallic nanoparticles, and vesicular carriers, etc. In this article, we have reviewed various conjugates of AmB with polymers and nanomaterials explored for its delivery to give a deep insight regarding further exploration in future. EXPERT OPINION: Covalent conjugates of AmB have been investigated by scientists, and preliminary in vitro and animal investigations have given successful results, which are required to be validated further with systematic investigation on safety and therapeutic efficacy in animals followed by clinical trials.


Assuntos
Anfotericina B , Nanoestruturas , Animais , Anfotericina B/uso terapêutico , Anfotericina B/toxicidade , Antifúngicos/uso terapêutico , Polímeros , Solubilidade , Portadores de Fármacos
11.
Stem Cells Int ; 2024: 9077926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213742

RESUMO

Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates a time-restricted event where the imbalance between pro- and antiangiogenic factors results in the transition from prevascular hyperplasia to outgrowing vascularized tumor, which eventually leads to the malignant cancer progression. In the last decade, molecular players, i.e., angiogenic biomarkers and underlying molecular pathways involved in tumorigenesis, have been intensely investigated. Disrupting the initiation and halting the progression of angiogenesis by targeting these biomarkers and molecular pathways has been considered as a potential treatment approach for tumor angiogenesis. This review discusses the currently known biomarkers and available antiangiogenic therapies in cancer, i.e., monoclonal antibodies, aptamers, small molecular inhibitors, miRNAs, siRNAs, angiostatin, endostatin, and melatonin analogues, either approved by the U.S. Food and Drug Administration or currently under clinical and preclinical investigations.

12.
Curr Pharm Des ; 29(10): 732-747, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999427

RESUMO

Recently, breast cancer has reached the highest incident rate amongst all the reported cancers, and one of its variants, known as triple-negative breast cancer (TNBC), is deadlier compared to the other types of breast cancer due to a lack of feasible diagnostic techniques. Advancements in nanotechnology have paved the way to formulate several nanocarriers with the ability to deliver anticancer drugs effectively and selectively to cancer cells with minimum side effects to non-cancerous cells. Nanotheranostics is a novel approach that can be used in the diagnosis of disease along with therapeutic effects. Currently, various imaging agents, such as organic dyes, radioactive agents, upconversion nanoparticles, various contrasting agents, quantum dots, etc., are being explored for the imaging of internal organs or to examine drug distribution. Furthermore, ligand-targeted nanocarriers, which have the potential to target cancer sites, are being used as advanced agents for cancer theranostic applications, including the identification of various metastatic sites of the cancerous tumor. This review article discusses the need for theranostic application in breast cancer with various imaging techniques, the latest nanotheranostic carriers in breast cancer, and related safety and toxicity issues, as well as highlights the importance of nanotheranostics in breast cancer, which could be helpful in deciphering questions related to nanotheranostic systems.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Nanomedicina Teranóstica/métodos , Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Portadores de Fármacos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
13.
Nanomedicine (Lond) ; 17(21): 1529-1546, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36416115

RESUMO

Aim: Bedaquiline fumarate (BQF), an antitubercular drug, shows limited bioavailability due to solubility-limited intestinal absorption. In this research, the authors formulated a BQF-loaded microemulsion to improve BQF's oral bioavailability. Methods: Microemulsion was prepared by a spontaneous emulsification method and evaluated for thermodynamic stability, size, dispersibility, transmittance, rheology, microrheology, drug release, cytotoxicity and cellular uptake. Results: Microemulsion showed an average globule size of 26.50 ± 6.29 nm with spherical geometry and revealed gel-sol-gel behavior in microrheological studies. Cytotoxicity and cell uptake studies in Caco-2 cells showed that BQF microemulsion was cytocompatible at the highest concentration of 500 µg/ml with significantly higher cellular uptake than control. Conclusion: The present study indicates that BQF microemulsion could be explored further for effective treatment of multidrug-resistant tuberculosis.


Assuntos
Tensoativos , Humanos , Células CACO-2 , Solubilidade , Reologia , Emulsões , Disponibilidade Biológica , Tamanho da Partícula
14.
Curr Infect Dis Rep ; 24(11): 189-204, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187900

RESUMO

Purpose of Review: Japanese encephalitis (JE), a clinical indication of JE virus-induced brain inflammation, is the most prevalent cause of viral encephalitis in the world. This review gives a comprehensive update on the epidemiology, clinical features, therapeutic trials and approaches for preventing the spread of JE. It also outlines the different JE vaccines used in various countries and recommendations for administration of JE vaccines. Recent Findings: According to the WHO, annual incidence of JE is estimated to be approximately 68,000 cases worldwide. It is widespread across Asia-Pacific, with a potential for worldwide transmission. In endemic locations, JE is believed to affect children below 6 years of age, but in newly affected areas, both adults and children are at risk due to a lack of protective antibodies. Various vaccines have been developed for the prevention of JE and are being administered in endemic countries. Summary: JE is a neuroinvasive disease that causes symptoms ranging from simple fever to severe encephalitis and death. Despite a vast number of clinical trials on various drugs, there is still no complete cure available, and it can only be prevented by adequate vaccination. Various nanotechnological approaches for the prevention and treatment of JE are outlined in this review. Supplementary Information: The online version contains supplementary material available at 10.1007/s11908-022-00786-1.

15.
Nanomedicine (Lond) ; 17(11): 793-812, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35587031

RESUMO

Infectious diseases are prevalent and have contributed to high morbidity rates by creating havoc like the COVID-19, 1918 influenza and Black Death (the plague) pandemics. Antimicrobial resistance, adverse effects, the emergence of co-infections and the high cost of antimicrobial therapies are major threats to the health of people worldwide while impacting overall healthcare and socioeconomic development. One of the most common ways to address this issue lies in improving existing antimicrobial drug-delivery systems. Nanoemulsions and their modified forms have been successfully employed for the delivery of antimicrobials to treat infectious diseases. In this article, the authors comprehensively reviewed how nanoemulsion-based formulation systems are shifting the paradigm for therapeutics and diagnosis of infectious diseases.


Assuntos
Anti-Infecciosos , Tratamento Farmacológico da COVID-19 , Doenças Transmissíveis , Antibacterianos , Doenças Transmissíveis/tratamento farmacológico , Emulsões , Humanos
16.
Artigo em Inglês | MEDLINE | ID: mdl-35997100

RESUMO

Breast cancer is one of the most frequently diagnosed cancers in women and the major cause of worldwide cancer-related deaths among women. Various treatment strategies including conventional chemotherapy, immunotherapy, gene therapy, gene silencing and deliberately engineered nanomaterials for receptor mediated targeted delivery of anticancer drugs, antibodies, and small-molecule inhibitors, etc are being investigated by scientists to combat breast cancer. Smartly designed/fabricated nanomaterials are being explored to target breast cancer through enhanced permeation and retention effect; and also, being conjugated with suitable ligand for receptor-mediated endocytosis to target breast cancer for diagnostic, and theranostic applications. These receptor-targeted nanomedicines have shown efficacy to target specific tumor tissue/cells abstaining the healthy tissues/cells from cytotoxic effect of anticancer drug molecules. In the last few decades, theranostic nanomedicines have gained much attention among other nanoparticle systems due to their unique ability to deliver chemotherapeutic as well as diagnostic agents, simultaneously. Theranostic nanomaterials are emerging as novel paradigm with ability for concurrent delivery of imaging (with contrasting agents), targeting (with biomarkers), and anticancer therapeutics with one delivery system (as cancer theranostics) and can transpire as promising strategy to overcome various hurdles for effective management of breast cancer including its most aggressive form, triple-negative breast cancer.


Assuntos
Antineoplásicos , Nanopartículas , Nanoestruturas , Neoplasias de Mama Triplo Negativas , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Nanomedicina , Nanopartículas/uso terapêutico , Nanoestruturas/uso terapêutico , Medicina de Precisão , Nanomedicina Teranóstica , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
17.
Nanomedicine ; 7(3): 295-304, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21070888

RESUMO

The present investigation was aimed at developing and comparing the cancer-targeting potential of ligand-anchored dendrimers. Folate-, dextran-, and galactose-anchored poly(propylene imine) dendrimers were synthesized and characterized. Dendritic formulations were evaluated for ex vivo cytotoxicity on HeLa and SiHa cell lines. Flow cytometry studies were performed on the HeLa cell line. An ex vivo MTT assay on HeLa cells indicated IC(50) values of 0.05, 0.2, 0.8, and 0.08 µM for folate, dextran, and galactose formulations, and for free paclitaxel (PTX), respectively. An analogous observation was carried out in SiHa cells, where IC(50) values of 0.6, 0.8, 10, and 6 µM were observed by folate, dextran, and galactose formulations, and free PTX, respectively. The outcome of the MTT assay and flow cytometry suggested the order of targeting potential of various ligands under investigation as folate > dextran > galactose. The outcome is deemed to be of scientific value and is believed to assist drug delivery scientists during selection of targeting ligands. FROM THE CLINICAL EDITOR: The cancer targeting potential of folate, dextran and galactose functionalized polypropyleneimine (PPI) dendrimers was studied by this group of investigators, reporting the order of targeting potential as folate > dextran > galactose.


Assuntos
Dendrímeros/química , Dextranos/química , Ácido Fólico/química , Galactose/química , Neoplasias/patologia , Polipropilenos/química , Bioensaio , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/síntese química , Citometria de Fluxo , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Ligantes , Especificidade de Órgãos/efeitos dos fármacos , Paclitaxel/farmacologia
18.
Nanomaterials (Basel) ; 11(2)2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33562310

RESUMO

Three-dimensional (3D) printing is gaining numerous advances in manufacturing approaches both at macro- and nanoscales. Three-dimensional printing is being explored for various biomedical applications and fabrication of nanomedicines using additive manufacturing techniques, and shows promising potential in fulfilling the need for patient-centric personalized treatment. Initial reports attributed this to availability of novel natural biomaterials and precisely engineered polymeric materials, which could be fabricated into exclusive 3D printed nanomaterials for various biomedical applications as nanomedicines. Nanomedicine is defined as the application of nanotechnology in designing nanomaterials for different medicinal applications, including diagnosis, treatment, monitoring, prevention, and control of diseases. Nanomedicine is also showing great impact in the design and development of precision medicine. In contrast to the "one-size-fits-all" criterion of the conventional medicine system, personalized or precision medicines consider the differences in various traits, including pharmacokinetics and genetics of different patients, which have shown improved results over conventional treatment. In the last few years, much literature has been published on the application of 3D printing for the fabrication of nanomedicine. This article deals with progress made in the development and design of tailor-made nanomedicine using 3D printing technology.

19.
Pharmaceutics ; 13(12)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34959321

RESUMO

Breast cancer therapeutic intervention continues to be ambiguous owing to the lack of strategies for targeted transport and receptor-mediated uptake of drugs by cancer cells. In addition to this, sporadic tumor microenvironment, prominent restrictions with conventional chemotherapy, and multidrug-resistant mechanisms of breast cancer cells possess a big challenge to even otherwise optimal and efficacious breast cancer treatment strategies. Surface-modified nanomedicines can expedite the cellular uptake and delivery of drug-loaded nanoparticulate constructs through binding with specific receptors overexpressed aberrantly on the tumor cell. The present review elucidates the interesting yet challenging concept of targeted delivery approaches by exploiting different types of nanoparticulate systems with multiple targeting ligands to target overexpressed receptors of breast cancer cells. The therapeutic efficacy of these novel approaches in preclinical models is also comprehensively discussed in this review. It is concluded from critical analysis of related literature that insight into the translational gap between laboratories and clinical settings would provide the possible future directions to plug the loopholes in the process of development of these receptor-targeted nanomedicines for the treatment of breast cancer.

20.
Pharm Nanotechnol ; 7(4): 259-278, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961518

RESUMO

Most of the active pharmaceutical ingredient used in the management of disease have poor water solubility and offer grueling problems in drug formulation development since low solubility is generally associated with poor dissolution characteristics which leads to poor oral bioavailability. The great challenge for the development of a pharmaceutical product is to create its new formulation and drug delivery system to limit solubility problems of existing drug candidate. Limited drug-loading capacity requires a large amount of carrier material to get appropriate encapsulation of the drug, which is another major challenge in the development of pharmaceutical product which could be resolved by developing nanocrystals (NCs). A significant research in the past few years has been done to develop NCs which helps in the delivery of poorly water soluble drugs via different routes. The technology could continue to thrive as a useful tool in pharmaceutical sciences for the improvement of drug solubility, absorption and bioavailability. Many crystalline compounds have pulled in incredible consideration much of the time, due to their ability to show good physical and chemical properties when contrasted with their amorphous counterparts. Nanocrystals have been proven to show atypical properties compared to the bulk. This review article explores the principles of the important nanocrystallization techniques including NCs characterization and its application.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Preparações Farmacêuticas/química , Disponibilidade Biológica , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Humanos , Preparações Farmacêuticas/administração & dosagem
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