RESUMO
The intricate process of protein binding orchestrates crucial drug interactions within the bloodstream, facilitating the formation of soluble complexes. This research endeavours to improve the dissolution and oral bioavailability of Rifampicin (RMP) by strategically manipulating drug-protein binding dynamics and the hydrophobic characteristics of human serum albumin (HSA). Various precipitation techniques leveraging methanol, ammonium sulfate, and heat treatment were meticulously employed to tailor the properties of colloidal albumin (HSA NPs). The resultant complexes underwent comprehensive characterization encompassing evaluations of hydrophobicity, size distribution, surface charge, and structural analyses through FTIR, TG-DSC, XRD, and morphological examinations. The findings revealed a significant binding affinity of 78.07 ± 6.6% with native albumin, aligning with prior research. Notably, the complex RMP-HSA NPs-M13, synthesized via the methanolic precipitation method, exhibited the most substantial complexation, achieving a remarkable 3.5-fold increase, followed by the ammonium sulfate (twofold) and heat treatment (1.07-fold) methods in comparison to native albumin binding. The gastric simulated media exhibited accelerated drug release kinetics, with maximal dissolution achieved within two hours, contrasting with the prolonged release observed under intestinal pH conditions. These findings translated into significant improvements in drug permeation, as evidenced by pharmacokinetic profiles demonstrating elevated Cmax, AUC, t1/2, and MRT values for RMP-HSA NPs-M13 compared to free RMP. In summary, this innovative approach underscores the potential of precipitation methods in engineering stable colloidal carrier systems tailored to enhance the oral bioavailability of poorly soluble drugs, offering a pragmatic and scalable alternative to conventional surfactants, polymers, or high-energy methods for complex formation and production.
Assuntos
Disponibilidade Biológica , Liberação Controlada de Fármacos , Rifampina , Solubilidade , Rifampina/farmacocinética , Rifampina/química , Rifampina/administração & dosagem , Administração Oral , Animais , Humanos , Precipitação Química , Interações Hidrofóbicas e Hidrofílicas , Albumina Sérica Humana/química , Nanopartículas/química , Ratos , Ligação Proteica , Masculino , Sulfato de Amônio/químicaRESUMO
INTRODUCTION: Luteolin (LUT), a naturally occurring flavonoid found in vegetables, fruits, and herbal medicines, has been extensively studied for its pharmacological activities, including anti-proliferative and anticancer effects on various cancer lines. It also exhibits potent antioxidant properties and pro-apoptotic activities against human cancers. However, its therapeutic potential is hindered by its poor solubility in water (5 µg/ml at 45°C) and low bioavailability. This research on the development of luteolin-loaded nanocarrier aims to overcome these limitations, thereby opening up new possibilities in cancer treatment. METHODS: This paper covers several nanoformulations studied to increase the solubility and bioavailability of LUT. The physicochemical characteristics of the nanoformulation that influence luteolin's solubility and bioavailability have been the subject of more in-depth investigation. Furthermore, it examines how LUT's anti-inflammatory and antioxidant properties aid in lessening the side effects of chemotherapy. RESULTS: Most nanoformulations, including phytosomes, lipid nanoparticles, liposomes, protein nanoparticles, polymer micelles, nanoemulsions, and metal nanoparticles, have shown promising results in improving the solubility and bioavailability of LUT. This is a significant step forward in enhancing the therapeutic potential of LUT in cancer treatment. Furthermore, the study found that LUT's ability to scavenge free radicals can significantly reduce the side effects of cancer treatment, further highlighting its potential to improve patient outcomes. CONCLUSION: Nanoformulations, because of their unique surface and physiochemical properties, improve the solubility and bioavailability of LUT. However, poor in-vitro and in-vivo correlation and scalability of nanoformulations need to be addressed to achieve good clinical performance of LUT in oncology.
RESUMO
The challenges in treating oral cancer include the limited effectiveness and systemic side effects of conventional chemotherapy and radiation therapy. Hyaluronic acid (HA) based Glycyrrhizin (GL) and Methotrexate (MT) loaded localized delivery systems, specifically nanofiber (NF) based platforms, were developed to address these challenges. The electrospinning method was used for the successful fabrication of a homogenous NF membrane and characterized for morphology, drug entrapment efficiency, tensile strength, and ex-vivo mucoadhesive study. Also, it was evaluated for in-vitro drug release profile, ex-vivo drug permeability, in-vitro anti-inflammatory, apoptosis assay by MTT and flow, and against specific cell lines in order to determine their potential for therapeutic use. Superior tensile breaking force (50 g), mucoadhesive strength of 153 gm/cm2, drug permeability, and releasing properties of designed NF, making them perfect requirements for oral cavity delivery. The anticancer potential of MT in the MTT assay and flow cytometry analysis was significantly increased in oral epidermal carcinoma cell (KB cell) for drug-loaded NF with 63.97 ± 1.99 % apoptosis, at 24 h. With these incorporated, GL with MT in NF had an anti-inflammatory potential, also demonstrated in-vitro and in-vivo. In the Ehrlich Ascites Carcinoma (EAC) induced mice model, the optimal formulation's shows better potential for tumor regression when comparing the developed NF formulation to the drugs. Experimental results show that by lowering mucositis-related inflammation and enhancing the effectiveness of oral cancer treatment, a developed nanofiber-based local drug delivery system offers a feasible strategy for managing oral cancer.
Assuntos
Apoptose , Liberação Controlada de Fármacos , Ácido Glicirrízico , Ácido Hialurônico , Metotrexato , Neoplasias Bucais , Nanofibras , Ácido Hialurônico/química , Nanofibras/química , Animais , Metotrexato/administração & dosagem , Metotrexato/química , Metotrexato/farmacologia , Neoplasias Bucais/tratamento farmacológico , Humanos , Ácido Glicirrízico/química , Ácido Glicirrízico/administração & dosagem , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Masculino , Portadores de Fármacos/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologiaRESUMO
The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9 nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5 mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2 µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo.
Assuntos
Anti-Inflamatórios não Esteroides , Antifúngicos , Biofilmes , Candida albicans , Candidíase Vulvovaginal , Quitosana , Reagentes de Ligações Cruzadas , Nanopartículas , Ácido Fítico , Biofilmes/efeitos dos fármacos , Ácido Fítico/química , Ácido Fítico/farmacologia , Ácido Fítico/uso terapêutico , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/farmacologia , Reagentes de Ligações Cruzadas/uso terapêutico , Quitosana/química , Quitosana/farmacologia , Quitosana/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Testes de Sensibilidade Microbiana , Citocinas/imunologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Feminino , Animais , Camundongos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/metabolismo , Vagina/microbiologiaRESUMO
Cervical cancer (CC) is the fourth leading cancer type in females globally. Being an ailment of the birth canal, primitive treatment strategies, including surgery, radiation, or laser therapy, bring along the risk of infertility, neonate mortality, premature parturition, etc. Systemic chemotherapy led to systemic toxicity. Therefore, delivering a smaller cargo of therapeutics to the local site is more beneficial in terms of efficacy as well as safety. Due to the regeneration of cervicovaginal mucus, conventional dosage forms come with the limitations of leaking, the requirement of repeated administration, and compromised vaginal retention. Therefore, these days novel strategies are being investigated with the ability to combat the limitations of conventional formulations. Novel carriers can be engineered to manipulate bioadhesive properties and sustained release patterns can be obtained thus leading to the maintenance of actives at therapeutic level locally for a longer period. Other than the purpose of CC treatment, these delivery systems also have been designed as postoperative care where a certain dose of antitumor agent will be maintained in the cervix postsurgical removal of the tumor. Herein, the most explored localized delivery systems for the treatment of CC, namely, nanofibers, nanoparticles, in situ gel, liposome, and hydrogel, have been discussed in detail. These carriers have exceptional properties that have been further modified with the aid of a wide range of polymers in order to serve the required purpose of therapeutic effect, safety, and stability. Further, the safety of these delivery systems toward vital organs has also been discussed.
Assuntos
Antineoplásicos , Nanopartículas , Neoplasias do Colo do Útero , Feminino , Recém-Nascido , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Lipossomos , HidrogéisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Glinus oppositifolius (L.) Aug. DC. belongs to the family Molluginaceae, an annual prostrate herb traditionally used to treat inflammations, arthritis, malarial, wounds, fevers, diarrhoea, cancer, stomach discomfort, jaundice, and intestinal parasites. However, the anti-arthritic activity of the aerial part has still not been reported. AIM OF THE STUDY: To investigate the antioxidant and anti-arthritic activity of G. oppositifolius in Complete Freund's Adjuvant (CFA) induced rats. MATERIALS AND METHODS: The dried aerial parts of this plant material were defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The in vitro anti-arthritic activity of methanolic extract of G. oppositifolius (MEGO) was evaluated in protein denaturation, membrane stabilization, and inhibition of proteinase assay at 25, 50, 100, 200, and 400 µg/ml concentrations. Female Wistar rats were immunized sub-dermally into the right hind paw with 0.1 ml of CFA. Rats were administered with MEGO at doses of 200 and 400 mg/kg once daily for fourteen days after arthritis induction. Assessment of arthritis was performed by measuring paw diameter, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters, followed by the analysis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1-beta (IL-1ß), cyclooxygenase-2 (COX-2), interleukin 13 (IL-13) and interleukin 10 (IL-10) and histopathological study. In vivo antioxidant effect was investigated in enzymatic assays. The presence of phytoconstituents was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. In silico molecular docking study of the compounds was carried out against COX-2, IL-1ß, IL-6, and TNF-α using AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. RESULTS: MEGO's in vitro anti-arthritic activity showed dose-dependent inhibition of protein denaturation, membrane stabilization, and proteinase inhibition, followed by significant in vivo anti-arthritic activity. The rats treated with MEGO showed tremendous potential in managing arthritis-like symptoms by restoring hematological, biochemical, and histological changes in CFA-induced rats. MEGO (200 and 400 mg/kg) showed a significant alleviation in the levels of hyper expressed inflammatory mediators (TNF-α, IL-1ß, and IL-6) and oxidative stress (SOD, CAT, GSH, and LPO) in CFA-induced rats. Spergulagenin-A as identified by LC-MS analysis, exhibited the highest binding affinity against COX-2 (-8.6), IL-1ß (7.2 kcal/mol), IL-6 (-7.4 kcal/mol), and TNF-α (-6.5 kcal/mol). CONCLUSIONS: Provided with the comprehensive investigation, methanolic extract of G. oppositifolius against arthritic-like condition is a proof of concept that revalidates its ethnic claim. The presence of Spergulagenin-A might be responsible for the anti-arthritic activity.
Assuntos
Artrite Experimental , Molluginaceae , Ratos , Animais , Fator de Necrose Tumoral alfa , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Interleucina-6 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ratos Wistar , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Quimiometria , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Metanol/química , Antioxidantes/uso terapêutico , Interleucina-13 , Peptídeo Hidrolases , Componentes Aéreos da PlantaRESUMO
Drug delivery to the buccal mucosa is one of the most convenient ways to treat common mouth problems. Here, we propose a spray-dried re-dispersible mucoadhesive controlled release gargle formulation to improve the efficacy of chlorhexidine. The present investigation portrays an approach to get stable and free-flowing spray-dried porous aggregates of chlorhexidine-loaded sodium alginate nanoparticles. The ionic gelation technique aided with the chlorhexidine's positive surface charge-based crosslinking, followed by spray drying of the nanoparticle's dispersion in the presence of lactose- and leucine-yielded nano-aggregates with good flow properties and with a size range of about 120-350 nm. Provided with the high entrapment efficiency (87%), the particles showed sustained drug release behaviors over a duration of 10 h, where 87% of the released drug got permeated within 12 h. The antimicrobial activity of the prepared formulation was tested on S. aureus, provided with a higher zone of growth inhibition than the marketed formulation. Aided with an appropriate mucoadhesive strength, this product exhibited extended retention of nanoparticles in the throat region, as shown by in vivo imaging results. In conclusion, the technology, provided with high drug retention and extended effect, could be a potential candidate for treating several types of throat infections.
Assuntos
Clorexidina , Faringe , Staphylococcus aureus , Sistemas de Liberação de Medicamentos/métodos , Preparações de Ação Retardada , Antissépticos Bucais , Tamanho da PartículaRESUMO
Bacterial vaginosis (BV) is a recurring infection that is difficult to treat due to the limited bioavailability of antimicrobials. In this study, Metronidazole (MTZ)-loaded chitosan nanoparticles (MCSNP) were synthesized employing phytic acid (PA) as a crosslinking agent for treating bacterial vaginosis. The prepared MCSNPs were characterized for size, shape, surface charge, compatibility, cytotoxicity, biofilm inhibition, and in-vitro/in-vivo antimicrobial activities. Morphological examination revealed that nanoparticles generated from 0.535 % w/v chitosan and 0.112 % w/v PA were non-spherical, discontinuous, and irregular, with zeta potential ranging from 25.00 ± 0.45 to 39 ± 0.7. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. The optimized formulation demonstrates a cumulative drug release of about 98 ± 1.5 % within 8 h. Antimicrobial studies demonstrated that the optimized formulation had enhanced efficacy against acid-adapted BV pathogens, with a MIC value of 0.9 ± 0.1 µg/mL. Compared to the MTZ alone, the in-vivo antibacterial results of in the case of developed nanoparticles showed a four-fold reduction in bacterial count in female Swiss albino mice. Based on the experimental findings, it was concluded that MCSNPs, due to their excellent physiochemical and antibacterial properties, could serve as a potential topical alternative for treating BV.
Assuntos
Quitosana , Nanopartículas , Vaginose Bacteriana , Animais , Feminino , Camundongos , Antibacterianos/química , Quitosana/química , Portadores de Fármacos/química , Metronidazol/farmacologia , Nanopartículas/química , Ácido Fítico , Polieletrólitos , Vaginose Bacteriana/tratamento farmacológicoRESUMO
Bacterial vaginosis (BV) is a recurring, chronic infection that is difficult to treat due to the limited bioavailability of antimicrobials within vaginal epithelial cells. Vaginal administration, because of lower dosing and systemic exposure offers a viable option for treating vaginal infections. In this study, Metronidazole-loaded chitosan nanoparticles were synthesised employing borax (BX) or tannic acid (TA) as an antimicrobial crosslinking agent for treating BV. The prepared NPs were characterized for various physical, physicochemical, pharmaceutical, thermal and antibacterial properties. Morphological investigation revealed that nanoparticles prepared from 0.5 % w/v chitosan, 1.2 % w/v BX, and 0.4 % w/v metronidazole (MTZ) were non-spherical, with particle sizes of 377.4 ± 37.3 nm and a zeta potential of 34 ± 2.1 mV. The optimised formulation has MIC values of 24 ± 0.5 and 59 ± 0.5 µg/mL, against Escherichia coli (E.coli) and Candida albicans (C.albicans) respectively. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. Under simulated vaginal fluid, the optimised formulation demonstrates a cumulative drug release of about 90 % within 6h. The prepared borax crosslinked NPs exhibit anti-fungal activities by inhibiting ergosterol synthesis. The in-vivo antibacterial data indicated a comparable reduction in bacterial count compared to the marketed formulation in female Swiss albino mice treated with optimised nanoparticles. According to histopathological findings, the prepared nanoparticle was safe for vaginal use. Based on the experimental findings, it was concluded that MBCSNPs, due to their good physiochemical and antimicrobial properties, could serve as a potential topical alternative for treating BV and reducing fungal infection.
Assuntos
Quitosana , Nanopartículas , Vaginose Bacteriana , Feminino , Humanos , Animais , Camundongos , Metronidazol/farmacologia , Vaginose Bacteriana/tratamento farmacológico , Quitosana/química , Portadores de Fármacos/química , Antibacterianos/química , Nanopartículas/química , Tamanho da PartículaRESUMO
Glycyrrhizin (GL) is the principal constituent of Glycyrrhiza glabra, having antiallergic, anticancer, anti-inflammatory, and antimicrobial action. The reverse-phase high-performance liquid chromatography (RP-HPLC) analytical method was used to quantitatively estimate GL in a nanoformulation and validated as per International Conference on Harmonization Q2 (R1) standards. A stationary phase of the C18-HL reversed-phase column and a mobile phase of acetonitrile and water were used for effective elution. The chromatographic conditions of RP-HPLC were optimized utilizing a quality-by-design approach to accomplish the required chromatographic separation of GL from its nanoformulation with minimal experimental runs. Optimized RP-HPLC conditions for the assay method consist of acetonitrile (41%) and water, pH 1.8, balanced with phosphoric acid (0.1%) as a mobile phase with a flow rate of 1 mL/min. The retention time was found at 7.25 min, and method validation confirmed its sensitivity, preciseness, accuracy, and robustness.
Assuntos
Cromatografia de Fase Reversa , Ácido Glicirrízico , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Acetonitrilas/química , ÁguaRESUMO
Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl ß-cyclodextrin (HP-ßCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-ßCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl ß-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-ßCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-ßCD NF displayed improved release (46.6 ± 2.16% in 5 min) and dissolution profiles (water dissolvability ≤ 6 s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-ßCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1ß, TNF-α, and IL-6 were significantly lower in GL-HP-ßCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-ßCD NF could serve as a useful strategy for improving the therapeutic effects of GL.
Assuntos
Ácido Glicirrízico , Nanofibras , Ratos , Animais , 2-Hidroxipropil-beta-Ciclodextrina/química , Solubilidade , Ácido Glicirrízico/farmacologia , Nanofibras/química , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND: Viral disease is a well-known cause of a significant impact on economic losses and threatens developed and developing societies. High mutation rates and the lack of ability of conventional formulations to target specific cells pose substantial hurdles to the successful treatment of viral diseases.
Methods: We conducted a preliminary search by a standard procedure. With hand searching, we conducted an advanced search across several electronic databases. After defining the selection criteria, two writers independently reviewed and evaluated the first 500 abstracts before screening the remaining 300. Since there was 97% agreement on the screening decisions, only one reviewer conducted the screening. The pre-planned data extraction process was accomplished, and the thoroughness of the description of participation techniques was assessed. Additional data extraction was carried out for articles with the most detailed illustrations. Four stakeholder representatives co-authored this systematic review. Results: Incorporating selective carbohydrate polymers into the antiviral pharmaceutical compositions could help to manage biological complications associated with viral infections. We included 172 papers in which authors were involved in a systematic review. The present review explains the role of carbohydrate polymers (chitosan, carrageenan, alginate, cyclodextrin, dextran, and heparin) in the prevention and treatment of viral infections in terms of their source, molecular weight, surface charge, chemical composition, and structure. Additionally, the review describes the primary mechanism of drug delivery performance of carbohydrate polymers to improve the antiviral properties and pharmacokinetic behaviour of lamivudine, zidovudine, acyclovir, etc. Conclusion: The article discussed the role of carbohydrate polymers in mitigating virus-induced associated complications like bacterial infection, cardiovascular disorder, oxidative stress, and metabolic disorder. As a result, this work will provide valuable information to scientists, researchers, and clinicians for suitable carbohydrate polymer-based pharmaceutical development.RESUMO
Malaria is a life-threatening parasitic disease transmitted by the infected female Anopheles mosquito. The development of drug tolerance and challenges related to the drugs' pharmacodynamic and pharmacokinetic parameters limits the antimalarial therapeutics response. Currently, nanotechnology-based drug delivery system provides an integrative platform for antimalarial therapy by improving the drug physicochemical properties, combating multidrug resistance, and lowering antimalarial drug-related toxicity. In addition, surface engineered nanocarrier systems offer a variety of alternatives for site-specific/targeted delivery of antimalarial therapeutics, anticipating better clinical outcomes at low drug concentrations and low toxicity profiles, as well as reducing the likelihood of the emergence of drug resistance. So, constructing nano carrier-based approaches for drug delivery has been considered the foremost strategy to combat malaria. This review focuses on the numerous nanotherapeutic strategies utilised to treat malaria as well as the benefits of nanotechnology as a potentially effective therapeutic.
Assuntos
Antimaláricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Malária , Animais , Feminino , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Nanomedicina , Malária/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Resistência a MedicamentosRESUMO
Microneedle arrays are micron-sized needles usually attached to a supporting base or patch facilitated drug delivery for systemic effects. Polyvinylpyrrolidone (PVP) is a lactam polymer containing an internal amide linkage. Because of its versatility and biocompatibility, it has been widely utilized to treat several skin, bone and eye problems. Due to its specific and unique properties, the researchers realize its utility as a polymer of tremendous potential. PVP-based dissolvable microneedles have widely been utilized as a carrier for delivering DNAs, proteins, vitamins, and several biological macromolecules transdermally. However, it does not get biodegraded into the body. Therefore, the presence of its fragments in the body post-treatment needs proper justification. The adequate justification for the fate of the fragment's end products in the body will allow even better utilization of PVP. This review analyses and illustrates various experimental findings to highlight the most recent advancements and applications of PVP microneedles in drug delivery systems and cosmetology and the potential for PVP microneedles in treating dermal and systemic disorders. This review presents the expected mode of PVP biodegradation in aqueous and soil environments as a waste material, its inertness, biocompatibility, and the importance of PVP as a fabricating material, pharmaceutical uses, and non-toxic profile.
Assuntos
Povidona , Pele , Microinjeções , Polímeros/metabolismo , Sistemas de Liberação de Medicamentos , Administração CutâneaRESUMO
Skin cancer, including basal cell carcinoma, melanoma, and squamous cell carcinoma, is conventionally treated by surgery, phototherapy, immunotherapy, and chemotherapy. For decades, surgical removal of malignant cancers has favored patients' therapeutic options. However, multiple aspects, such as the patient's comorbidities, the anatomical location of the lesion, and possible resistance to recurrent excisions, can influence the decision to conduct surgery. Therefore, topical and transdermal therapy may be a more appropriate option, allowing for higher therapeutic levels at the site of action and reducing toxicity than systemic therapy. The most commonly used topical agents for treating skin carcinoma are- 5-fluorouracil, imiquimod, sonidegib, dacarbazine, etc. However, physicochemical drug characteristics and skin physiological barriers limit the anticancer potency of topical as well as transdermal drug delivery. In recent years, unquestionable signs of progress have been demonstrated to circumvent these challenges. In particular, significant studies have been made, including modification of bio-actives, permeability enhancers, incorporation of advanced nano and microcarriers, and physical enhancement devices. This critical review summarizes the advancement in the chemical composition of bioactives used in skin cancer, such as sinecatechins, BIL-010t, patidegib, gingerol, curcumin, remetinostat, epigallocatechin-3-gallate, etc. Furthermore, this review specifically addresses the progress in transdermal delivery systems for melanoma and nonmelanoma cancer therapy, emphasizing advances in physical and chemical penetration enhancement and nanocarrier-assisted transdermal systems.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Sistemas de Liberação de Medicamentos , Administração Cutânea , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Melanoma/tratamento farmacológico , PeleRESUMO
Psoriasis is a chronic autoimmune pathological condition characterized by hyperactivation of proinflammatory cytokines (IL-6, TNF-α, IL-17, IL-23, etc.). Severe drug-associated toxicities like hepatotoxicity and nephrotoxicity (Methotrexate), teratogenicity (Tazarotene), hypercholesterolemia (Cyclosporine) and hypercalcemia (tacalcitol), are the forefront challenges that demand an alternative approach for the treatment of psoriasis. In the present study, a natural lead molecule 'Betulin' (BE, lup-20(29)-ene-3b,28-diol) was isolated from Betula utilis and subsequently, structure-based molecular docking was employed to identify the molecular target for psoriasis. The computational analysis reflects better affinity of BE towards pro-inflammatory cytokine as compared to standard drugs. Apart from this BE shows a greater affinity towards the overexpressed Glut-1 receptor in comparison to standard drug Metformin (Met). Based on the in silico screening the isolated lead compound was further processed for the evaluation of anti-psoriatic activity via imiquimod (IMQ 5%) induced psoriasis-like skin inflammation model. In vivo screening models were characterized by different parameters (psoriasis area and severity index (PASI) scores, macroscopically and behavioral evaluation, splenomegaly, cytokine levels and histological changes) and compared among the experimental groups. The experimental finding reflects comparable results of PASI score, i.e., 57.14% and 61.9% recovery of test BE-solution (180 mg/kg) and standard Betamethasone di-propionate ointment (BD-oint.0.5 mg/g), respectively. Focusing on other parameters, BE shows relative results such as an enhanced macroscopically with behavioral conditions, reducing the expression of proinflammatory cytokine as well as restoring histological changes with that of BD. These findings suggest that BE-isolated phytoconstituents from Betula utilis could be a potential agent and a step closer to psoriasis treatment. HIGHLIGHTPsoriasis is a multifaceted, immunologically mediated disease consequences production of high levels of proinflammatory mediators and overexpression of Glut-1 transporters that trigger keratinocyte proliferation and inflammatory cascades.A Himalayan silver birch, Betula utilis (Bhojpatra) contains many steroidal terpenes which are responsible for various pharmacological activities that could be exploited in drug development in psoriasis.The computational analysis of BE reflects a better affinity toward the proinflammatory cytokines with their target receptors and indicates a satisfactory range with a slight deviation from Jorgensen and Lipinski's rule and possesses a significant drug choice for psoriasis.Preclinical findings of BE-solution (BE-sol) give a positive response towards IMQ-induced psoriasis-like skin inflammation model.[Figure: see text]Communicated by Ramaswamy H. Sarma.
RESUMO
BACKGROUND: Chemotherapy for stomach cancer often includes several side effects. The primary reasons for the failure of such treatment approaches are low drug concentrations in target tissues and a short stomach residence time. OBJECTIVE: Gastroretentive controlled drug delivery systems improves the therapeutic performance of chemotherapeutic drugs following oral administration because of the longer gastric retention time. The goal of this study was to find suitable gastroretentive formulations that might be used for the localized treatment of stomach cancer. METHODS: The purpose of this study is to summarize current advances in gastro-retentive drug administration for oral chemotherapy, with a focus on floating, mucoadhesive, and swellable systems. This article also discusses the potentials and limitations of existing gastroretentive drug delivery systems used in cancer chemotherapy. RESULTS: Due to increased stomach retention and modified drug release properties, gastroretentive controlled drug delivery systems improve the therapeutic performance of anti-cancer drugs used to treat stomach cancer. CONCLUSION: Gastroretentive drug delivery systems appear to be a promising carrier for localized chemotherapy with smaller doses and better patient compliance. However, selection of drug candidates, drugfood interactions and chemotherapy-induced gastric discomfort remain the key characteristics that must be addressed to improve treatment outcomes.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Administração Oral , Preparações de Ação Retardada , Mucosa GástricaRESUMO
Antimicrobial-resistant (AMR) bacterial infections remain a significant public health concern. The situation is exacerbated by the rapid development of bacterial resistance to currently available antimicrobials. Metal nanoparticles represent a new perspective in treating AMR due to their unique mechanisms, such as disrupting bacterial cell membrane potential and integrity, biofilm inhibition, reactive oxygen species (ROS) formation, enhancing host immune responses, and inhibiting RNA and protein synthesis by inducing intracellular processes. Metal nanoparticles (MNPs) properties such as size, shape, surface functionalization, surface charges, and co-encapsulated drug delivery capability all play a role in determining their potential against multidrug-resistant bacterial infections. Silver, gold, zinc oxide, selenium, copper, cobalt, and iron oxide nanoparticles have recently been studied extensively against multidrug-resistant bacterial infections. This review aims to provide insight into the size, shape, surface properties, and co-encapsulation of various MNPs in managing multidrug-resistant bacterial infections.
Assuntos
Infecções Bacterianas , Nanopartículas Metálicas , Nanopartículas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções Bacterianas/tratamento farmacológico , Bactérias , Testes de Sensibilidade MicrobianaRESUMO
Breast cancer (BC) is the deadliest malignant disorder globally, with a significant mortality rate. The development of tolerance throughout cancer treatment and non-specific targeting limits the drug's response. Currently, nano therapy provides an interdisciplinary area for imaging, diagnosis, and targeted drug delivery for BC. Several overexpressed biomarkers, proteins, and receptors are identified in BC, which can be potentially targeted by using nanomaterial for drug/gene/immune/photo-responsive therapy and bio-imaging. In recent applications, magnetic iron oxide nanoparticles (IONs) have shown tremendous attention to the researcher because they combine selective drug delivery and imaging functionalities. IONs can be efficaciously functionalised for potential application in BC therapy and diagnosis. In this review, we explored the current application of IONs in chemotherapeutics delivery, gene delivery, immunotherapy, photo-responsive therapy, and bio-imaging for BC based on their molecular mechanism. In addition, we also highlighted the effect of IONs' size, shape, dimension, and functionalization on BC targeting and imaging. To better comprehend the functionalization potential of IONs, this paper provides an outline of BC cellular development. IONs for BC theranostic are also reviewed based on their clinical significance and future aspects.Graphical Abstract[Formula: see text].
Current Breast cancer treatment resists due to the development of drug tolerance throughout cancer treatment and non-specific drug targeting.Magnetic IONs are being utilised for the therapy and bio-imaging of breast cancer by targeting overexpressed biomarkers, proteins, and receptors in breast cancer progression.Physical properties of IONs, such as size, shape, and dimensions, also alter their therapeutic and imaging responses.Iron oxide nanoparticles can be efficaciously functionalised based on breast cancer molecular mechanisms for potential application in breast cancer drug delivery, gene delivery, immunotherapy, photo responsive therapy, and bio-imaging.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Medicina de Precisão , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas Magnéticas de Óxido de Ferro , Íons/uso terapêuticoRESUMO
Multidrug resistance (MDR) in cancer chemotherapy is a growing concern for medical practitioners. P-glycoprotein (P-gp) overexpression is one of the major reasons for multidrug resistance in cancer chemotherapy. The P-gp overexpression in cancer cells depends on several factors like adenosine triphosphate (ATP) hydrolysis, hypoxia-inducible factor 1 alpha (HIF-1α), and drug physicochemical properties such as lipophilicity, molecular weight, and molecular size. Further multiple exposures of anticancer drugs to the P-gp efflux protein cause acquired P-gp overexpression. Unique structural and functional characteristics of nanotechnology-based drug delivery systems provide opportunities to circumvent P-gp mediated MDR. The primary mechanism behind the nanocarrier systems in P-gp inhibition includes: bypassing or inhibiting the P-gp efflux pump to combat MDR. In this review, we discuss the role of P-gp in MDR and highlight the recent progress in different nanocarriers to overcome P-gp mediated MDR in terms of their limitations and potentials.