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1.
Saudi J Biol Sci ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34483699

RESUMO

Besides its impacts on governance, economics, human culture, geostrategic partnership and environment, globalization greatly exerted control over science and security policies. Biosecurity is the critical job of efforts, policy and preparation to protect health of human, animal and environmental against any biological threats. With the transition into a global village, the possibility of biosecurity breaches has significantly increased. The COVID-19 pandemic is an example of an infringement on biosecurity that has posed a serious threat to the world. Since the first report on the recognition of COVID-19, a number of governments have taken preventive measures, like; lockdown, screening and early detection of suspected and implementing the required response to protect the loss of life and economy. Unfortunately, some of these measures have only recently been taken in some countries, which have contributed significantly to an increased morbidity and loss of life on a daily basis. In this article, the biological risks affecting human, animal and environmental conditions, biosafety violations and preventive measures have been discussed in order to reduce the outbreak and impacts of a pandemic like COVID-19.

2.
Drug Deliv ; 28(1): 1836-1848, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34515597

RESUMO

Natamycin (NT) is a synthetic broad-spectrum antifungal used in eye drops. However, it has low solubility and high molecular weight, limiting its permeation, and generally causes eye discomfort or irritation when administered. Therefore, the present study aimed to develop an ophthalmic in situ gel formulation with NT-loaded cubosomes to enhance ocular permeation, improve antifungal activity, and prolong the retention time within the eye. The NT-loaded cubosome (NT-Cub) formula was first optimized using an I-optimal design utilizing phytantriol, PolyMulse, and NT as the independent formulation factors and particle size, entrapment efficiency %, and inhibition zone as responses. Phytantriol was found to increase particle size and entrapment efficiency %. Higher levels of PolyMulse slightly increased the inhibition zone whereas a decrease in particle size and EE% was observed. Increasing the NT level initially increased the entrapment efficiency % and inhibition zone. The optimized NT-Cub formulation was converted into an in situ gel system using 1.5% Carbopol 934. The optimum formula showed a pH-sensitive increase in viscosity, favoring prolonged retention in the eye. The in vitro release of NT was found to be 71 ± 4% in simulated tear fluid. The optimum formulation enhanced the ex vivo permeation of NT by 3.3 times compared to a commercial formulation and 5.2 times compared to the NT suspension. The in vivo ocular irritation test proved that the optimum formulation is less irritating than a commercial formulation of NT. This further implies that the developed formulation produces less ocular irritation and can reduce the required frequency of administration.

3.
Int J Nanomedicine ; 16: 6345-6366, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34556985

RESUMO

Background: Ticagrelor (TG), an antiplatelet drug is employed to treat patients with acute coronary syndrome, but its inadequate oral bioavailability due to poor solubility and low permeability restricts its effectiveness. Purpose: This contemporary work was aimed to design a novel pH-sensitive nanocomposite hydrogel (NCH) formulation incorporating thiolated chitosan (TCH) based nanoparticles (NPs) of Ticagrelor (TG), to enhance its oral bioavailability for effectively inhibiting platelet aggregation. Methods: NCHs were prepared by free radical polymerization technique, using variable concentrations of chitosan (CH) as biodegradable polymer, acrylic acid (AA) as a monomer, N,N-methylene bisacrylamide (MBAA) as cross-linker, and potassium persulphate (KPS) as initiator. Results: The optimum hydrogel formulation was selected for fabricating NCHs, considering porosity, sol-gel fraction, swelling studies, drug loading capacity, and TG's in vitro release as determining factors. Outcomes of the studies have shown that the extent of hydrogel swelling and drug release was comparatively greater at higher pH (7.4). Moreover, an amplifying trend was observed for drug loading and hydrogel swelling by increasing AA content, while it declined by increasing MBAA. The NCHs were evaluated by various physicochemical techniques and the selected formulation was subjected to in vivo bioavailability studies, confirming enhancement of bioavailability as indicated by prolonged half-life and multifold increase in area under the curve (AUC) as compared to pure TG. Conclusion: The results suggest that NCHs demonstrated a pH-responsive, controlled behavior along with enhanced bioavailability. Thus NCHs can be effectively utilized as efficient delivery systems for oral delivery of TG to reduce the risk of myocardial infarction.

4.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443336

RESUMO

We develop a suitable delivery system for niaouli essential oil (NEO) using a nanoemulsification method for acne vulgaris. Prepared nanoemulsions (NEs) were characterized for droplet dimension, rheology, surface charge, and stability. The ability of NEO formulations against Propionibacterium acnes and Staphylococcus epidermidis was investigated and all formulations showed antiacne potential in vitro. Ex vivo permeation studies indicated significant improvement in drug permeations and steady state flux of all NEO-NEs compared to the neat NEO (p < 0.05). On the basis of the studied pharmaceutical parameters, enhanced ex vivo skin permeation, and marked effect on acne pathogens, formulation NEO-NE4 was found to be the best (oil (NEO; 10% v/v); Kolliphor EL (9.25% v/v), Carbitol (27.75% v/v), and water (53% v/v)). Concisely, the in vitro and ex vivo results revealed that nanoemulsification improved the delivery as well as bioactivities of NEO significantly.


Assuntos
Portadores de Fármacos/química , Melaleuca/química , Nanoestruturas/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Emulsões , Óleos Voláteis/metabolismo , Permeabilidade , Pele/metabolismo , Staphylococcus epidermidis/efeitos dos fármacos
5.
Pharmaceutics ; 13(8)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34452179

RESUMO

INTRODUCTION: Luteolin (LUT) is natural flavonoid with multiple therapeutic potentials and is explored for transdermal delivery using a nanocarrier system. LUT loaded cationic nanoemulsions (CNE1-CNE9) using bergamot oil (BO) were developed, optimized, and characterized in terms of in vitro and ex vivo parameters for improved permeation. MATERIALS AND METHODS: The solubility study of LUT was carried out in selected excipients, namely BO, cremophor EL (CEL as surfactant), labrasol (LAB), and oleylamine (OA as cationic charge inducer). Formulations were characterized with globular size, polydispersity index (PDI), zeta potential, pH, and thermodynamic stability studies. The optimized formulation (CNE4) was selected for comparative investigations (% transmittance as %T, morphology, chemical compatibility, drug content, in vitro % drug release, ex vivo skin permeation, and drug deposition, DD) against ANE4 (anionic nanoemulsion for comparison) and drug suspension (DS). RESULTS: Formulations such as CNE1-CNE9 and ANE4 (except CNE6 and CNE8) were found to be stable. The optimized CNE4 based on the lowest value of globular size (112 nm), minimum PDI (0.15), and optimum zeta potential (+26 mV) was selected for comparative assessment against ANE4 and DS. The %T values of CNE1-CNE9 were found to be ˃95% and CEL content slightly improved the %T value. The spherical CNE4 was compatible with excipients and showed % total drug content in the range of 97.9-99.7%. In vitro drug release values from CNE4 and ANE4 were significantly higher than DS. Moreover, permeation flux (138.82 ± 8.4 µg/cm2·h), enhancement ratio (8.23), and DD (10.98%) were remarkably higher than DS. Thus, ex vivo parameters were relatively high as compared to DS which may be attributed to nanonization, surfactant-mediated reversible changes in skin lipid matrix, and electrostatic interaction of nanoglobules with the cellular surface. CONCLUSION: Transdermal delivery of LUT can be a suitable alternative to oral drug delivery for augmented skin permeation and drug deposition.

6.
Int J Nanomedicine ; 16: 5465-5478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413644

RESUMO

Introduction: Natural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation's aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health. Methods: Several OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities. Results: The NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats. Conclusion: This study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.

7.
Cutan Ocul Toxicol ; : 1-12, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34340615

RESUMO

Background:Conventional delivery systems like solution and suspension are commonly used for the treatment of ocular diseases but have low corneal residence time and hence the duration of effect is limited. These drawbacks of conventional systems can be reduced by preparing bioadhesive chitosan (CH) coated noisome.Methods: Niosomes (NIM) of carteolol (CT) were developed by the thin-film hydration method and optimised by the Box-Behnken statistical design. Further, the optimised CT-NIM was coated with CH to enhance the ocular residence time . The optimised formulation was evaluated for vesicle size, entrapment efficiency, and in-vitro drug release and transcorneal permeation, histopathology, etc.Results: CT-NIM-opt showed the vesicle size and entrapment efficiency of 235 ± 3.54 nm, and 70.45 ± 0.87%, respectively. DSC spectra exhibited that CT was completely encapsulated into the CH-CT-NIM matrix. Drug release from CH-CT-NIM-opt was more sustained (68.28 ± 4.2%) than CT-NIM (75.69 ± 4.5% in 12 h) and CT solution (99.89 ± 2.8% in 4 h). The CH-CT-NIM-opt represented a strong bio-adhesion (89.76 ± 3.6%) than CT-NIM-opt (15.65 ± 3.4%). The permeation flux exhibited 1.13-fold higher permeation than CT-NIM and 3.23 fold than CT solution. The corneal hydration was found to be within the limit value. The histopathology study exhibited no structural damage to the cornea . HET-CAM results showed zero scores indicating no bleeding or haemorrhage. CH-CT-NIM-opt was found to be isotonic and exhibited good stability when stored at 4 °C for the stated duration of time.Conclusion: The above findings suggested that NIM can be a potential carrier for the delivery of CT with better ocular residence time.

8.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202080

RESUMO

Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family mediates an important role in recognizing and mounting an immune response against intruding microbes. TLR-9 is a member of the intracellular TLR family, which recognizes unmethylated CG motifs from the prokaryotic genome. Upon its activation, TLR-9 triggers downstream of the MyD-88-dependent transcriptional activation of NF-κB, and subsequently results in abundant inflammatory cytokines expression that induces a profound inflammatory milieu. The present exploratory investigation aimed at elucidating the potency of schizophyllan for entrapping ODN 1826 (SPG-ODN 1826)-mediated stimulation of TLR-9 in provoking an inflammatory-type response in murine alveolar macrophages. Schizophyllan (SPG), a representative of the ß-glucan family, was used in the present study as a nanovehicle for endosomal trafficking of CpG ODN 1826. TEM analysis of SPG-ODN 1826 nanovehicles revealed that the prepared nanovehicles are spherical and have an average size of about 100 nm. Interestingly, SPG-ODN 1826 nanovehicles were competent in delivering their therapeutic payload within endosomes of murine alveolar macrophage (J774A.1) cells. Exposure of these nanovehicles within LPS stimulated J774A.1, resulted in a significant provocation of reactive oxygen species (ROS) (p < 0.01) in comparison to CpG ODN 1826 alone. Moreover, the formulated nanovehicles succeeded in generating a profound Th1-based cytokine profile constituted by enhanced expression of IFN-γ (p < 0.001) and IL-1ß (p < 0.001) inflammatory cytokines. These findings clearly indicated the immunostimulatory potential of SPG-ODN 1826 nanovehicles for inducing the Th1-type phenotype, which would certainly assist in skewing M2 phenotype into the much-desired M1 type during lung cancer.


Assuntos
Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Nanoestruturas/química , Oligodesoxirribonucleotídeos/química , Sizofirano/química , Receptor Toll-Like 9/agonistas , Animais , Sobrevivência Celular , Citocinas/metabolismo , Endossomos , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Ativação de Macrófagos/imunologia , Camundongos , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Tamanho da Partícula
9.
Biomed Pharmacother ; 141: 111829, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34147904

RESUMO

The current study focuses on development of nasal mucoadhesive microspheres for nose-to-brain delivery of rivastigmine for Alzheimer treatment. A systematic development was employed for optimization of the formulation and process parameters influential on the quality attributes of the microspheres. The risk assessment study revealed major influence of the polymer concentration (ethylcellulose: chitosan), the concentration of surfactant solution (polyvinyl alcohol), and stirring speed as the critical factors for optimization of the microspheres. These factors were systematically optimized using Box-Behnken design and microspheres were evaluated for the particle size, entrapment efficiency, and in vitro drug release as the response variables. The optimized microspheres containing 4.4% wt/vol polymers, 1% wt/vol surfactant, and stirring speed at 1500 rpm showed particle size of 19.9 µm, entrapment efficiency of 77.8%, and drug release parameters as T80% of 7.3 h. The surface modification of microspheres was performed with lectin by carbodiimide activation reaction and confirmed by difference in surface charge before and after chemical functionalization by zeta potential measurement which was found to be - 25.7 mV and 20.5 mV, respectively. Ex vivo study for bioadhesion strength evaluation on goat nasal mucosa indicated a significant difference (p < 0.001) between the plain (29%) and lectin functionalized microspheres (64%). In vivo behavioral and biochemical studies in the rats treated with lectin functionalized microspheres showed markedly better memory-retention vis-à-vis test and pure drug solution treated rats (p < 0.001). In a nutshell, the present studies showed successful development of nasal microspheres for enhanced brain delivery of rivastigmine for Alzheimer's treatment.

10.
Drug Deliv ; 28(1): 1043-1054, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34060397

RESUMO

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34071692

RESUMO

The study aimed to prepare green nanoemulsion (GNE) multi-components ((water/dimethyl sulfoxide-transcutol/isopropyl alcohol/capmul MCM C8 (CMC8)) to remove rifampicin (RIF) from a contaminated aqueous bulk solution. Pseudo ternary phase diagrams dictated several batches of GNE prepared following the reported method. Selected nanoemulsions (NF1-NF5) were characterized for morphology, globular size, size distribution (polydispersity index, PDI), viscosity, zeta potential, refractive index (RI), and free-thaw kinetic stability. They were investigated for percent removal efficiency (%RE) of RIF from the bulk aqueous solution for varied time intervals (10-60 min). Finally, scanning electron microscopy-energy dispersive x-ray (SEM-EDX) and inductive coupled plasma-optical emission system (ICP-OE) were used to confirm the extraction of trace content of dimethyl sulfoxide (DMSO) and others in the treated water. Considering the data obtained for globule size, PDI, viscosity, zeta potential, freeze-thaw stability, and refractive index, NF5 was the most suitable for RIF removal. The largest %RE value (91.7%) was related to NF5, which may be prudent to correlate with the lowest value (~39 nm) of size (maximum surface area available for contact adsorption), PDI (0.112), and viscosity (82 cP). Moreover, %RE was profoundly influenced by the content of CMC8 and the aqueous phase. These two phases had immense impact on the viscosity, size, and RI. The percent content of water, Smix, and CMC8 were 15% w/w), 60% w/w, and 25% w/w, respectively in NF5. SEM-EDX and ICP-OE confirmed the absence of DMSO and other hydrophilic components in the treated water. Thus, efficient NF5 could be a promising option to the conventional method to decontaminate the polluted aqueous system.


Assuntos
Nanopartículas , Rifampina , Adsorção , Emulsões , Tamanho da Partícula , Viscosidade , Água
12.
AAPS PharmSciTech ; 22(5): 194, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34184161

RESUMO

The study aimed to identify a suitable cosolvent + water mixture for subcutaneous (sub-Q) delivery of ketoconazole (KETO). The solubility was assessed for several dimethyl acetamide (DMA) + water mixtures at T = 293.2 to 318.2 K and pressure P = 0.1 MPa. The experimental solubility (xe) was validated using the Van 't Hoff and Yalkowsky models and functional thermodynamic parameters (enthalpy ΔsolH°, entropy ΔsolS°, and Gibbs free energy ΔsolG°). The in vitro drug release study was performed at physiological pH, and the data served as the input to GastroPlus, which predicted the in vivo performance of KETO dissolved in a DMA + water cosolvent mixture for sub-Q delivery in human. The maximum solubility (mole fraction) of KETO (9.81 × 10-1) was obtained for neat DMA at 318.2 K whereas the lowest value (1.7 × 10-5) was for pure water at 293.2 K. An apparent thermodynamic analysis based on xe gave positive values for the functional parameters. KETO dissolution requires energy, as evidenced by the high positive values of ΔsolH° and ΔsolG°. Interestingly, ΔsolG° progressively decreased with increasing concentration of DMA in the DMA + water mixture, suggesting that the DMA-based molecular interaction improved the solubilization. Positive values of ΔsolG° and ΔsolS° for each DMA + water cosolvent mixture corroborated the endothermic and entropy-driven dissolution. GastroPlus predicted better absorption of KETO through sub-Q delivery than oral delivery. Hence, the DMA + water mixture may be a promising system for sub-Q delivery of KETO to control topical and systemic fungal infections.


Assuntos
Antifúngicos/farmacocinética , Simulação por Computador , Cetoconazol/farmacocinética , Modelos Biológicos , Antifúngicos/química , Previsões , Humanos , Cetoconazol/química , Reprodutibilidade dos Testes , Solubilidade , Solventes/química , Solventes/farmacocinética , Água/química
13.
Molecules ; 26(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072306

RESUMO

The present research work is designed to prepare and evaluate piperine liposomes and piperine-chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (-7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.


Assuntos
Alcaloides/química , Benzodioxóis/química , Quitosana/química , Lipossomos/química , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Antineoplásicos/química , Antioxidantes/química , Adesão Celular , Sobrevivência Celular , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Técnicas In Vitro , Concentração Inibidora 50 , Células MCF-7 , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Permeabilidade , Espectroscopia de Infravermelho com Transformada de Fourier
14.
AAPS PharmSciTech ; 22(5): 177, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34128106

RESUMO

Fluvastatin (FLV) is known to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), which is over-expressed in various cancers. FLV has been reported to decrease cancer development and metastasis. However, because of low bioavailability, extensive first-pass metabolism and short half-life of FLV (1.2 h), it is not appropriate for clinical application. Therefore, FLV-loaded emulsomes were formulated and optimized using Box-Behnken experimental design to achieve higher efficiency of formulation. Antitumor activity of optimized FLV-loaded emulsomes was evaluated in prostate cancer cells using cell cytotoxicity, apoptotic activity, cell cycle analysis, and enzyme-linked immunosorbent assay. The FLV-loaded emulsomes exhibited a monodispersed size distribution with a mean particle size less than 100 nm as measured by zetasizer. The entrapment efficiency was found to be 93.74% with controlled drug release profile. FLV-EMLs showed a significant inhibitory effect on the viability of PC3 cells when compared to the free FLV (P < 0.0025). Furthermore, FLV-EMLs showed significant arrest in G2/M and increase in percentage of apoptotic cells as compared to free FLV. FLV-EMLs were more effective than free FLV in reducing mitochondrial membrane potential and increase in caspase-3 activity. These results suggesting that FLV-EMLs caused cell cycle arrest which clarifies its significant antiproliferative effect compared to the free drug. Therefore, optimized FLV-EMLs may be an effective carrier for FLV in prostate cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Citotoxinas/farmacologia , Portadores de Fármacos/farmacologia , Fluvastatina/farmacologia , Neoplasias da Próstata , Antineoplásicos/síntese química , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citotoxinas/síntese química , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/síntese química , Fluvastatina/síntese química , Humanos , Masculino , Células PC-3 , Tamanho da Partícula
15.
Drug Deliv ; 28(1): 973-984, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34036860

RESUMO

The major limitation with the oral administration of most of the phytochemicals is their low aqueous solubility and bioavailability. Thymoquinone (THQ) is one of the most widely used phytochemicals used to treat a variety of diseases. However, strong lipophilic characteristics limit its clinical application. Therefore, this study was aimed to design novel chitosan (C) modified polycaprolactone (PL) nanoparticles (NPs) for improved oral bioavailability of THQ. THQ-CPLNPs was optimized 33-Box-Behnken design. After that, the optimized THQ-CPLNPs was characterized by different parameters. THQ-CPLNPs showed the size, PDI, and ZP of 182.32 ± 6.46 nm, 0.179 ± 0.012, and +21.36 ± 1.22 mV, respectively. The entrapment and loading capacity were found to be 79.86 ± 4.36%, and 13.45 ± 1.38%, respectively. THQ-CPLNPs exhibited burst release in initial 2 h followed by prolonged release up to 24 h in simulated intestinal fluids. THQ-CPLNPs showed excellent mucoadhesion properties which were further confirmed with the intestinal permeation study as well as confocal microscopy. The study revealed higher permeation of THQ-CPLNPs compared to neat THQ suspension (THQ-S). Moreover, in vivo gastric irritation study revealed good compatibility of THQ-CPLNPs with the gastric mucosa. Furthermore, pharmacokinetic results depicted ∼3.53-fold improved oral bioavailability of THQ from THQ-CPLNPs than THQ-S. Therefore, from the findings, it was concluded that the prepared polymeric NPs could be an effective delivery system for improved oral bioavailability of THQ.

16.
AAPS PharmSciTech ; 22(5): 161, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031791

RESUMO

Atorvastatin (ATV) is a poorly water-soluble drug that exhibits poor oral bioavailability. Therefore, present research was designed to develop ATV solid dispersions (SDs) to enhance the solubility, drug release, and oral bioavailability. Various SDs of ATV were formulated by conventional and microwave-induced melting methods using Gelucire®48/16 as a carrier. The formulated SDs were characterized for different physicochemical characterizations, drug release, and oral bioavailability studies. The results obtained from the different physicochemical characterization indicate the molecular dispersion of ATV within various SDs. The drug polymer interaction results showed no interaction between ATV and used carrier. There was marked enhancement in the solubility (1.95-9.32 folds) was observed for ATV in prepared SDs as compare to pure ATV. The drug content was found to be in the range of 96.19% ± 2.14% to 98.34% ± 1.32%. The drug release results revealed significant enhancement in ATV release from prepared SDs compared to the pure drug and the marketed tablets. The formulation F8 showed high dissolution performance (% DE30 value of 80.65 ± 3.05) among the other formulations. Optimized Gelucire®48/16-based SDs formulation suggested improved oral absorption of atorvastatin as evidenced with improved pharmacokinetic parameters (Cmax 2864.33 ± 573.86 ng/ml; AUC0-t 5594.95 ± 623.3 ng/h ml) as compared to ATV suspension (Cmax 317.82 ± 63.56 ng/ml; AUC0-t 573.94 ± 398.9 ng/h ml) and marketed tablets (Cmax 852.72 ± 42.63 ng/ml; 4837.4 ± 174.7 ng/h ml). Conclusively, solid dispersion-based oral formulation of atorvastatin could be a promising approach for enhanced drug solubilization, dissolution, and subsequently improved absorption.


Assuntos
Atorvastatina/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Administração Oral , Animais , Atorvastatina/sangue , Atorvastatina/química , Disponibilidade Biológica , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Técnicas In Vitro , Ratos , Solubilidade , Comprimidos
17.
PLoS One ; 16(4): e0249485, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831070

RESUMO

The aim of this work was to solubilize simvastatin (SIM) using different micellar solutions of various non-ionic surfactants such as Tween-80 (T80), Tween-20 (T20), Myrj-52 (M52), Myrj-59 (M59), Brij-35 (B35) and Brij-58 (B58). The solubility of SIM in water (H2O) and different micellar concentrations of T80, T20, M52, M59, B35 and B58 was determined at temperatures T = 300.2 K to 320.2 K under atmospheric pressure p = 0.1 MPa using saturation shake flask method. The experimental solubility data of SIM was regressed using van't Hoff and Apelblat models. The solubility of SIM (mole fraction) was recorded highest in M59 (1.54 x 10-2) followed by M52 (6.56 x 10-3), B58 (5.52 x 10-3), B35 (3.97 x 10-3), T80 (1.68 x 10-3), T20 (1.16 x 10-3) [the concentration of surfactants was 20 mM in H2O in all cases] and H2O (1.94 x 10-6) at T = 320.2 K. The same results were also recorded at each temperature and each micellar concentration of T80, T20, M52, M59, B35 and B58. "Apparent thermodynamic analysis" showed endothermic and entropy-driven dissolution/solubilization of SIM in H2O and various micellar solutions of T80, T20, M52, M59, B35 and B58.


Assuntos
Micelas , Modelos Moleculares , Sinvastatina/química , Tensoativos/química , Conformação Molecular , Polietilenoglicóis/química , Solubilidade , Solventes/química , Termodinâmica , Água/química
18.
Molecules ; 26(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800115

RESUMO

Graphene oxide (GO), due to its 2D planar structure and favorable physical and chemical properties, has been used in different fields including drug delivery. This study aimed to investigate the impact of different process parameters on the average size of drug-loaded PEGylated nano graphene oxide (NGO-PEG) particles using design of experiment (DoE) and the loading of drugs with different molecular structures on an NGO-PEG-based delivery system. GO was prepared from graphite, processed using a sonication method, and functionalized using PEG 6000. Acetaminophen (AMP), diclofenac (DIC), and methotrexate (MTX) were loaded onto NGO-PEG particles. Drug-loaded NGO-PEG was then characterized using dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), XRD. The DLS data showed that the drug-loaded NGO-PEG suspensions were in the size range of 200 nm-1.3 µm. The sonication time and the stirring rate were found to be the major process parameters which affected the average size of the drug-loaded NGO-PEG. FTIR, DSC, XRD, and SEM demonstrated that the functionalization or coating of the NGO occurred through physical interaction using PEG 6000. Methotrexate (MTX), with the highest number of aromatic rings, showed the highest loading efficiency of 95.6% compared to drugs with fewer aromatic rings (diclofenac (DIC) 70.5% and acetaminophen (AMP) 65.5%). This study suggests that GO-based nano delivery systems can be used to deliver drugs with multiple aromatic rings with a low water solubility and targeted delivery (e.g., cancer).


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Grafite/química , Nanopartículas/química , Acetaminofen/administração & dosagem , Acetaminofen/química , Varredura Diferencial de Calorimetria , Diclofenaco/administração & dosagem , Diclofenaco/química , Portadores de Fármacos/química , Metotrexato/administração & dosagem , Metotrexato/química , Microscopia Eletrônica de Varredura , Estrutura Molecular , Nanopartículas/administração & dosagem , Tamanho da Partícula , Polietilenoglicóis/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
19.
Pharmaceutics ; 13(3)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802156

RESUMO

Recently, drug delivery using natural biological carriers has emerged as one of the most widely investigated topics of research. Erythrocytes, or red blood cells, can act as potential carriers for a wide variety of drugs, including anticancer, antibacterial, antiviral, and anti-inflammatory, along with various proteins, peptides, enzymes, and other macromolecules. The red blood cell-based nanocarrier systems, also called nanoerythrosomes, are nanovesicles poised with extraordinary features such as long blood circulation times, the ability to escape immune system, the ability to release the drug gradually, the protection of drugs from various endogenous factors, targeted and specified delivery of drugs, as well as possessing both therapeutic and diagnostic applications in various fields of biomedical sciences. Their journey over the last two decades is escalating with fast pace, ranging from in vivo to preclinical and clinical studies by encapsulating a number of drugs into these carriers. Being biomimetic nanoparticles, they have enhanced the stability profile of drugs and their excellent site-specific targeting ability makes them potential carrier systems in the diagnosis and therapy of wide variety of tumors including gliomas, lung cancers, breast cancers, colon cancers, gastric cancers, and other solid tumors. This review focuses on the most recent advancements in the field of nanoerythrosomes, as an excellent and promising nanoplatform for the novel drug delivery of various drugs particularly antineoplastic drugs along with their potential as a promising diagnostic tool for the identification of different tumors.

20.
Foods ; 10(3)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805719

RESUMO

This study aimed to perform a systematic review on gluten-free bread formulations using specific volumes as a quality indicator. In this systematic review, we identified 259 studies that met inclusion criteria. From these studies, 43 met the requirements of having gluten-free bread with a specific volume greater than or equal to 3.5 cm3/g. Other parameters such as the texture profile, color (crumb and crust), and sensory analysis examined in these studies were presented. The formulations that best compensated the lack of the gluten-network were based on the combination of rice flour, rice flour with low amylose content, maize flour, rice starch, corn starch, potato starch, starch with proteins and added with transglutaminase (TGase), and hydrocolloids like hydroxypropylmethylcellulose (HPMC). Of the 43 studies, three did not present risk of bias, and the only parameter evaluated in common in the studies was the specific volume. However, it is necessary to jointly analyze other parameters that contribute to the quality, such as texture profile, external and internal characteristics, acceptability, and useful life of the bread, especially since it is a product obtained through raw materials and unconventional ingredients.

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