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Although the use of thermoplastic polyurethane (Tpu) nanofiber mats as wound dressings is of great interest due to their mechanical properties, they are hindered by their poor wettability and bioavailability. In this study, we aimed to improve the cellular affinity of Tpu nanofiber mats for skin disorders by incorporating extracted collagen (Col) from tendons and physically mixed with a layer of phytoceramides (Phyto) to produce TpuCol@X-Phyto mats in which the weight % of Phyto relatively to the weight of the solution was X = 0.5, 1.0, or 1.5 wt% via facile electrospinning approach. The collective observations strongly indicate the successful incorporation and retention of Phyto within the TpuCol architecture. An increase in the Phyto concentration decreased the water contact angle from 69.4° ± 3.47° to 57.9° ± 2.89°, demonstrating improvement in the hydrophilicity of Tpu and binary blend TpuCol nanofiber mats. The mechanical property of 1.0 wt% Phyto aligns with practical requirements owing to the presence of two hydroxyl groups and the amide linkage likely contributing to various hydrogen bonds, providing mechanical strength to the channel structure and a degree of rigidity essential for transmitting mechanical stress. The proliferation of human skin fibroblast (HSF) peaked significantly 100 % with TpuCol@X-Phyto mats coated for X =1.0 and 1.5 wt% of Phyto. Electrospun scaffolds with the highest Phyto content have shown the lowest degree of hemolysis, demonstrating the high level of compatibility between them and blood. The TpuCol@1.5Phyto mat also demonstrated higher efficacy in antibacterial and antioxidant activities, achieving a rate of DPPH radical scavenging of 83.3 % for this latter property. The most notable wound closure among all tested formulations was attributed to higher Phyto. Thus, the developed TpuCol@1.5Phyto nanofiber formula exhibited enhanced healing in an in vitro epidermal model.
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Colágeno , Nanofibras , Poliuretanos , Nanofibras/química , Poliuretanos/química , Humanos , Colágeno/química , Dermatopatias/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Fibroblastos/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bandagens , Cicatrização/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos dos fármacos , Interações Hidrofóbicas e HidrofílicasRESUMO
Depression, the second biggest cause of disability worldwide, is widespread. Many antidepressant medications, including Desvenlafaxine Succinate (D.V.S.), function by elevating neurotransmitter levels at the synapse through the inhibition of reabsorption by neurons. However, the effectiveness of these treatments is often limited by their inability to reach the brain using conventional administration methods. Bilosome-stabilized nanovesicles containing bile salts have drawn much interest because of their adaptability and versatility in various applications. This study aimed to address this issue by formulating intranasal bilosomes incorporated into a mucoadhesive in situ gel to deliver D.V.S. directly to the brain for depression treatment. The desvenlafaxine-loaded bilosomes were developed using a thin film hydration method based on the l-optimal design. They were intended to provide a more convenient route of administration for antidepressants, enhancing bioavailability and brain targeting through intranasal delivery. The study assessed the optimized bilosomes for particle size (311.21 ± 0.42 nm), Zeta potential (-37.35 ± 0.43)and encapsulation efficiency (99.53 ± 0.41%) and further evaluated them in ex vivo and in vivo pharmacokinetics studies. Pharmacokinetic data reveal enhanced brain uptake compared to a free drug. A statistically optimized bilosome formulation was determined. The intranasal administration of mucoadhesive in situ gel containing desvenlafaxine succinate-loaded bilosomes facilitated direct nose-to-brain drug delivery, improving brain bioavailability.
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Aim: Our investigation aims to estimate the antifungal effect of propranolol hydrochloride (PNL). Methods: Oleosomes (OLs) were fabricated by thin-film hydration and evaluated for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and amount of drug released after 6 h Q6h (%). Results: The optimal OL showed a rounded shape with optimum characteristics. The ex-vivo permeation and confocal laser scanning microscopy verified the prolonged release and well deposition of PNL-loaded OLs-gel. The in-silico assessment demonstrated the good stability of PNL with OLs' ingredients. In vivo evaluations for PNL-loaded OLs-gel showed a good antifungal impact against Candida albicans with good safety. Conclusion: This work highlights the potential of PNL-loaded OLs-gel as a potential treatment for candida vaginal infection.
[Box: see text].
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Antifúngicos , Candida albicans , Quitosana , Hidrogéis , Propranolol , Candida albicans/efeitos dos fármacos , Propranolol/química , Propranolol/farmacologia , Propranolol/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/administração & dosagem , Feminino , Animais , Quitosana/química , Hidrogéis/química , Tamanho da Partícula , Humanos , Liberação Controlada de Fármacos , Lipossomos/química , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Portadores de Fármacos/química , Vagina/microbiologia , Vagina/efeitos dos fármacosRESUMO
Nanocomposite alginate hydrogel containing Propranolol hydrochloride (PNL) cerosomes (CERs) was prepared as a repurposed remedy for topical skin Methicillin-Resistant Staphylococcus aureus (MRSA) infection. CERs were formed via an ethanol injection technique using different ceramides, Kolliphores® as a surfactant, and Didodecyldimethylammonium bromide (DDAB) as a positive charge inducer. CERs were optimized utilizing 13. 22 mixed-factorial design employing Design-Expert® software, the assessed responses were entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimum CER, composed of 5 mg DDAB, ceramide VI, and Kolliphor® RH40 showed tubular vesicles with EE% of 92.91 ± 0.98%, PS of 388.75 ± 18.99 nm, PDI of 0.363 ± 0.01, and ZP of 30.36 ± 0.69 mV. Also, it remained stable for 90 days and manifested great mucoadhesive aspects. The optimum CER was incorporated into calcium alginate to prepare nanocomposite hydrogel. The ex-vivo evaluation illustrated that PNL was permeated in a more prolonged pattern from PNL-loaded CERs nanocomposite related to PNL-composite, optimum CER, and PNL solution. Confocal laser scanning microscopy revealed a perfect accumulation of fluorescein-labeled CERs in the skin. The in-silico investigation illustrated that the PNL was stable when mixed with other ingredients in the CERs and confirmed that PNL is a promising candidate for curing MRSA. Moreover, the PNL-loaded CERs nanocomposite revealed superiority over the PNL solution in inhibiting biofilm formation and eradication. The PNL-loaded CERs nanocomposite showed superiority over the PNL-composite for treating MRSA infection in the in-vivo mice model. Histopathological studies revealed the safety of the tested formulations. In conclusion, PNL-loaded CERs nanocomposite provided a promising, safe cure for MRSA bacterial skin infection.
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In this study, a new gastro-floating sustained-release tablet (GFT) with a combination of Etoricoxib (ET) and Famotidine (FM) was successfully developed. GFTs were prepared by using a combination of hydrophilic swellable natural/semi-synthetic polymers as a controlled-release layer. Through a 24 full factorial statistical experimental design, the effects of formulation factors on the release of GFTs were conducted. The ideal floating tablet (FT) comprised konjac-gum (150 mg), guar-gum (26.57 mg), xanthan-gum (54.17 mg), and HPMC-K15-M (69.25 mg). The ideal FT exhibited a high swelling index (SI) (297.7%) and rapid FLT (around 50 s) in 0.1 N HCl as well as controlled release of ET (22.43% in 1 h and 77.47% in 8 h) and FM (24.89% in 1 h and 93.82% in 8 h) with the absence of any drug-excipient interactions. The AUC0â¼72 (ng h/mL) of ET and FM in the GFTs were approximately double-fold of the market, respectively. The relative bioavailability was (207.48 ± 12.02% and 208.51 ± 13.11%) compared with commercial tablets. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. These findings revealed the successful preparation of the sustained-release floating tablet with improved dual drug delivery.
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Preparações de Ação Retardada , Liberação Controlada de Fármacos , Etoricoxib , Famotidina , Comprimidos , Famotidina/administração & dosagem , Famotidina/farmacocinética , Famotidina/química , Etoricoxib/administração & dosagem , Etoricoxib/farmacocinética , Etoricoxib/química , Animais , Masculino , Coelhos , Excipientes/química , Disponibilidade BiológicaRESUMO
Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.
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Althaea , Quitosana , Diabetes Mellitus , Nanopartículas Metálicas , Óxido de Zinco , Humanos , Animais , Ratos , Óxido de Zinco/química , Quitosana/química , Althaea/metabolismo , Interleucina-6 , Fator de Necrose Tumoral alfa , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Cicatrização , Anti-Inflamatórios/farmacologia , Inflamação , Flores , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Mirtazapine (MZPc) is an antidepressant drug which is approved by the FDA. It has low bioavailability, which is only 50%, in spite of its rapid absorption when orally administered owing to high first-pass metabolism. This study was oriented towards delivering intranasal (IN) mirtazapine by a direct route to the brain by means of preparing lipid nanocapsules (LNCs) as a targeted drug delivery system. MZP-LNCs were constructed by solvent-free phase inversion temperature technique applying D-Optimal mixture design to study the impact of 3 formulation variables on the characterization of the formulated nanocapsules. Independent variables were percentage of Labrafac oil, percentage of Solutol and percentage of water. Dependent variables were particle size, polydispersity index (PDI), Zeta potential and solubilization capacity. Nanocapsules of the optimized formula loaded with MZP were of spherical shape as confirmed by transmission electron microscopy with particle diameter of 20.59 nm, zeta potential of - 5.71, PDI of 0.223 and solubilization capacity of 7.21 mg/g. The in vivo pharmacokinetic behavior of intranasal MZP-LNCs in brain and blood was correlated to MZP solution after intravenous (IV) and intranasal administration in mice. In vivo biodistribution of the drug in mice was assessed by a radiolabeling technique using radioiodinated mirtazapine (131I-MZP). Results showed that intranasal MZP-LNCs were able to deliver higher amount of MZP to the brain with less drug levels in blood when compared to the MZP solution after IV and IN administration. Moreover, the percentage of drug targeting efficiency (%DTE) of the optimized MZP-LNCs was 332.2 which indicated more effective brain targeting by the intranasal route. It also had a direct transport percentage (%DTP) of 90.68 that revealed a paramount contribution of the nose to brain pathway in the drug delivery to the brain.
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Administração Intranasal , Encéfalo , Lipídeos , Mirtazapina , Nanocápsulas , Animais , Mirtazapina/farmacocinética , Mirtazapina/administração & dosagem , Mirtazapina/química , Encéfalo/metabolismo , Distribuição Tecidual , Nanocápsulas/química , Lipídeos/química , Lipídeos/farmacocinética , Lipídeos/administração & dosagem , Masculino , Camundongos , Sistemas de Liberação de Medicamentos , Tamanho da Partícula , Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/administração & dosagem , Mucosa Nasal/metabolismo , Mianserina/farmacocinética , Mianserina/administração & dosagem , Mianserina/química , Mianserina/análogos & derivados , Mianserina/sangueRESUMO
The study aims to improve the ocular delivery of Nebivolol HCL (NBV) belonging to the Biopharmaceutics classification system (BCSII) by using spanlastic nanovesicles (SNVs) for ophthalmic delivery and incorporating them into hydroxypropyl methylcellulose gel with ketorolac tromethamine (KET) as an anti-inflammatory to improve glaucoma complications like Conjunctivitis. SNVs were prepared by ethanol injection technique using span (60) as a surfactant and labrasol as an edge activator (EA). The impact of formulation factors on SNVs properties was investigated using a Box-Behnken design. In vitro evaluations showed that the formulations (F1, F4, and F14), containing Span 60 and labrasol as EA (25%, 50%, and 25%), exhibited high EE% with low PS and high ZP and DI. Additionally, 61.72 ± 0.77%, 58.97 ± 1.44%, and 56.20 ± 2.32% of the NBV amount were released from F1, F4, and F14 after 5 h, compared to 93.94 ± 1.21% released from drug suspension. The selected formula (G1), containing F1 in combination with KET and 2% w/w HPMC, exhibited 76.36 ± 0.90% drug release after 12 h. Ex vivo Confocal laser scanning revealed a high penetration of NBV-SNVs gel that ascertained the results of the in-vitro study. In vivo studies showed a significant decrease in glaucoma compared to drug suspension, and histopathological studies showed improvement in glaucomatous eye retinal atrophy. G1 is considered a promising approach to improving ocular permeability, absorption, and anti-inflammatory activity, providing a safer alternative to current regimens.
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l-carnitine is an essential dietary supplement of physiological importance. Handling and manufacture of l-carnitine is difficult due to its hygroscopic nature, resulting in impairing its flow properties, as well as solid dosage form stability. The study aimed at reducing l-carnitine hygroscopicity through its encapsulation within a hydrophobic, pH-insensitive polymer. A solid in oil in oil (s/o/o) emulsion solvent evaporation technique for microencapsulation was adopted to exclude the possibility of water uptake. The polymers used were two ethyl cellulose (EC) grades with different viscosities. The chosen solvent for the polymer was acetone, and liquid paraffin was the dispersion medium in which both the drug and polymer were insoluble. Sixteen formulations were developed, and evaluated to study the formulation parameters as anti-coalescent type, mixing speed, surfactant type and polymer ratio, and viscosity grade. A "One Factor at A Time" (OFAT) design of experiment, and a factorial design were utilized. Study results revealed that successful microencapsulation occurred by using Aerosil 200 (0.1 %) as anti-coalescent, a mixing speed of 1000 rpm, and Ethocel Std 20 at a 3:1 drug-to-polymer ratio. Microcapsule formulation containing l-carnitine base, successfully compressed into tablets, showed acceptable water content, disintegration time, hardness, and dissolution. Moreover, it showed acceptable stability upon storage at 40 °C at 75 % RH for six months compared to l-carnitine tablets prepared by wet granulation.
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Obesity has been associated with the occurrence and prevalence of various chronic metabolic diseases. The management of obesity has evolved to focus not only on reducing weight, but also on preventing obesity-related complications. Studies have shown that bioactive components in natural products like white kidney bean extract (WKBE), propolis ethanolic extract (PEE), and chromium picolinate (CrPi3) showed anti-obesity properties. However, no studies have examined the outcomes of combining any of these nutraceutical supplements. We compared the effects of HFD supplemented with WKBE, WKBE+PEE, or WKBE+PEE+CrPi3 against control and obese groups using Sprague-Dawley rats fed a 45% high-fat diet as an in vivo model. Nutritional parameters, biochemical parameters, and biomarkers of cardiovascular disease, liver function, kidney function, and gut health were among the comparable effects. Our findings showed that combining the three nutraceutical supplements had a synergetic effect on reducing weight gain, food utilization rate, abdominal fat, serum lipids, arterial and hepatic lipids, risk of cardiovascular disease, and blood glucose level, in addition to improving renal function and gut microbiota. We attributed these effects to the α-amylase inhibitor action of WKBE, flavonoids, and polyphenol content of PEE, which were potentiated with CrPi3 resulting in a further reduction or normalization of certain parameters.
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Doenças Cardiovasculares , Phaseolus , Própole , Ratos , Animais , Ratos Sprague-Dawley , Própole/farmacologia , Dieta Hiperlipídica/efeitos adversos , Doenças Cardiovasculares/complicações , Extratos Vegetais/farmacologia , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/prevenção & controle , LipídeosRESUMO
In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 33. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.
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Acne Vulgar , Fármacos Dermatológicos , Humanos , Camundongos , Animais , Adapaleno , Acne Vulgar/tratamento farmacológico , Acne Vulgar/patologia , Pele/patologia , Polímeros/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Resultado do Tratamento , Géis/uso terapêuticoRESUMO
Nebivolol (NBV), a BCS class II anti-hypertensive drug, suffers from limited solubility and oral bioavailability. Nanosized ethosomes were adopted as an approach to solubilize and deliver NBV transdermally, as a substitute to oral route. Ethosomal dispersions were prepared employing thin film hydration method. Formulation variables were adjusted to obtain entrapment efficiency; EE > 50%, particle size; PS < 100 nm, zeta potential; ZP > ±25 mV, and polydispersity index; PDI < 0.5. The optimized ethosomal dispersion (OED) showed accepted EE 86.46 ± 0.15%, PS 73.50 ± 0.08 nm, ZP 33.75 ± 1.20 mV, and PDI 0.31 ± 0.07. It also showed enhanced cumulative amount of NBV permeated at 8 h (Q8) 71.26 ± 1.46% and 24 h (Q24) 98.18 ± 1.02%. TEM images denoted spherical vesicles with light colored lipid bi-layer and dark core. Confocal laser scanning microscopy showed deeply localized intradermal and transfollicular permeation of the fluorolabelled OED (FL-OED). Nanosized FL-OED (<100 nm) can permeate through hair follicles creating a drug reservoir for enhanced systemic absorption. OED formulated into transdermal patch (OED-TP1) exhibited accepted physicochemical properties including; thickness 0.14 ± 0.01 mm, folding endurance 151 ± 0.07, surface pH 5.80 ± 0.15, drug content 98.64 ± 2.01%, mucoadhesion 8534 ± 0.03, Q8 87.61 ± 0.11%, and Q24 99.22 ± 0.24%. In vivo pharmacokinetic studies showed significantly enhanced bioavailability of OED-TP1 by 7.9 folds compared to oral Nevilob® tablets (p = 0.0002). It could be concluded that OED-TP1 can be a promising lipid nanocarrier TDDS for NBV and an efficacious alternative route of administration for hypertensive patients suffering from dysphagia.
Ethosomes loaded with lipophilic drugs, as NBV, can have two possible pathways of permeation through the skin; intradermal and transfollicular.Nanosized ethosomes (< 100 nm) can produce efficient intradermal and transfollicular reservoirs for sustained drug delivery.The formulated transdermal patch loaded with the optimized ethosomal dispersion (OED) showed enhanced bioavailability by 7.9 folds compared to Nevilob® oral tablets.
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Lipídeos , Pele , Humanos , Nebivolol , Administração Cutânea , Microscopia Confocal , Tamanho da Partícula , Lipossomos/químicaRESUMO
This study aims to improve the RXB bioavailability using hybrid nanoparticles. A modified melt dispersion technique created different formulas with varying GMO-SAIB: RXB and GMO: SAIB ratios, with fixed GMO-SAIB: poloxamer 407 ratios. The PS, PDI, ZP, and EE were measured to determine the optimal formula, which was selected using Design-Expert™ software. The optimized formula was lyophilized and tested for PS, PDI, ZP, and EE. The chosen lyophilized formula (L4) was characterized using FTIR, DSC, PXRD, dissolution studies, and pharmacokinetics studies. The study found correlations between variables and identified how GMO-SAIB concentration affects drug encapsulation. The dissolution parameters were calculated, including % Q5 and % DE). The % Q5 values were 68.4 ± 1.7% and 89.7 ± 3.6% for Xarelto and L4 tablets, respectively. The % DE values were 89.7 ± 0.4% and 97.5 ± 2.1% for Xarelto and L4 tablets, respectively. The AUC values were 2117.0 ng.h/mL (±77.3) and 3919.4 ng.h/mL (±134.8) for Xarelto and L4 tablets, respectively. The Cmax values were 241.3 ng/mL (±21.0) and 521.5 ng/mL (±91.5) for Xarelto and L4 tablets, respectively. In conclusion, the study found that using GMO-SAIB as co-formers effectively enhanced the bioavailability of RXB. The authors recommend using the hybrid nanoparticles technique and suggest further research to enhance its effectiveness for drug delivery.
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Nanopartículas , Rivaroxabana , Plantas Geneticamente Modificadas , Disponibilidade Biológica , SacaroseRESUMO
Etoricoxib, as a model drug, has a poor solubility and dissolution rate. Cyclodextrin derivatives can be used to solve such a problem. A comparative study was run on three cyclodextrin derivatives, namely ß-CD, HP ß-CD, and SBE ß-CD, to solve the drug problem through the formulation of solid dispersions and their preparation into fast-dissolving tablets. Preparations utilized different (1:1, 1:2, and 1:4) drug:carrier ratios. Nine fast-dissolving tablets (containing 1:4 drug: carrier) were formulated using Prosolv ODT® and/or F-melt® type C as super-disintegrants. Optimized formulation was chosen based on a 32 factorial design. The responses chosen were the outcomes of the in vitro evaluation tests. The optimized formulation that had the highest desirability (0.86) was found to be SD-HP3, which was prepared from etoricoxib: HP ß-CD at a 1:4 ratio using equal amounts of Prosolv ODT® and F-melt® type C. An in vivo evaluation of SD-HP3 on a rabbit model revealed its superiority over the marketed product Arcoxia®. SD-HP3 showed a significantly lower Tmax (13.3 min) and a significantly higher Cmax (9122.156 µg/mL), as well as a significantly higher AUC, than Arcoxia®. Thus, the solubility, dissolution, and bioavailability of etoricoxib were significantly enhanced.
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Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.
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Diabetes Mellitus Tipo 2 , Nanopartículas , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Coelhos , Canagliflozina , Comprimidos/química , Solubilidade , Povidona/química , Permeabilidade , Nanopartículas/químicaRESUMO
This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 23 factorial design was conducted to address the impact of independent variables QAS type (X1), QAS to CHO molar ratio (X2), and sonication time (X3). The dependent variables were particle size (PS; Y1), polydispersity index (PDI; Y2), zeta potential (ZP; Y3), entrapment efficiency percent (EE%; Y4) and percent of drug released after 6 h (Q6%: Y5). Then, the selected quatsomes formula was incorporated into different gel bases to prepare an optimized mucoadhesive gel to be evaluated via in vivo study. The PS of the developed quatsomes ranged from 69.47 ± 0.41 to 113.28 ± 0.79 nm, the PDI from 0.207 ± 0.004 to 0.328 ± 0.004, ZP from 45.15 ± 0.19 to 68.1 ± 0.54 mV, EE% from 79.62 ± 1.44 to 98.60% ± 1.22 and Q6% from 58.39 ± 1.75 to 94.42% ± 2.15. The quatsomal mucoadhesive gel showed rapid recovery of ulcers, which was confirmed by the histological study and the evaluation of inflammatory biomarkers. These results assured the capability of the developed quatsomal mucoadhesive gel to be a promising formulation for treating buccal diseases.
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Green coffee bean extract (GCBE) provides diversified health benefits. However, its reported low bioavailability impeded its utilization in various applications. In this study, GCBE-loaded solid lipid nanoparticles (SLNs) were prepared to improve the bioavailability through enhanced intestinal absorption of GCBE. During the preparation of promising GCBE-loaded SLNs, the lipid concentration, surfactant concentration, and co-surfactant amount are crucial that were optimized using the Box-Behnken design, while particle size, polydispersity index (PDI), ζ-potential, entrapment efficiency, and cumulative drug release were the measured responses. GCBE-SLNs were successfully developed by a high shear homogenization technique using geleol as a solid lipid, tween 80 as a surfactant, and propylene glycol as Co-SAA. The optimized SLNs contained 5.8% geleol, 5.9% tween 80, and 80.4 mg PG resulting in a small particle size of 235.7 ± 12.5 nm, reasonably acceptable PDI of 0.417 ± 0.023, and ζ-potential of -15 ± 0.14 mV, with a high entrapment efficiency of 58.3 ± 0.85% and cumulative release of 7575 ± 0.78%. Furthermore, the performance of the optimized GCBE-SLN was evaluated using an ex vivo everted sac model where the intestinal permeation of GCBE was improved due to nanoencapsulation using SLN. Consequently, the results enlightened the auspicious potential of exploiting oral GCBE-SLNs for boosting intestinal absorption of chlorogenic acid.
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The study aims to investigate the ability of lyophilized nasal inserts of nanosized atomoxetine HCl solid lipid nanoparticles (ATM-SLNs) to transport atomoxetine (ATM) directly to the brain and overcome the first-pass metabolism. In this case, 16 formulae of (ATM-SLNs) were prepared using hot melt emulsification, stirring and ultrasonication method technique. A full factorial design was established with 24 trials by optimization of four variables; lipid type (Compritol 888 ATO or stearic acid) (X1), lipid to drug ratio [(1:2) or (2:1)] (X2), span 60: Pluronic f127 ratio [(1:3) or (3:1)] (X3) and probe sonication time (five or ten minutes) (X4). The prepared SLNs were characterized for entrapment efficiency (EE%), in-vitro drug release after 30 min (Q30min), particle size (PS), zeta potential (ZP) and polydispersity index (PDI). Design Expert® software was used to select the optimum two formulae. The morphological examination for the optimum two formulae was carried out using a transmission electron microscope (TEM). Furthermore, eight lyophilized nasal inserts were prepared by using a 23 full factorial design by optimization of three variables: type of (ATM-SLNs) formula (X1), type of polymer (NOVEON AA1 or HPMC K100m) (X2) and concentration of polymer (X3). They were evaluated for nasal inserts' physicochemical properties. The two optimum inserts were selected by Design Expert® software. The two optimum insets with the highest desirability values were (S4 and S8). They were subjected to DSC thermal stability study and in-vivo study on rats. They were compared with atomoxetine oral solution, atomoxetine (3 mg/kg, intraperitoneal injection) and the pure atomoxetine solution loaded in lyophilized insert. (ATM-SLNs) showed EE% range of (41.14 mg ± 1.8% to 90.6 mg ± 2.8%), (Q30min%) of (27.11 ± 5.9% to 91.08 ± 0.15%), ZP of (-8.52 ± 0.75 to -28.4 ± 0.212% mV), PS of (320.9 ± 110.81% nm to 936.7 ± 229.6% nm) and PDI of (0.222 ± 0.132% to 0.658 ± 0.03%). Additionally, the two optimum (ATM-SLNs) formulae chosen, i.e., F7 and F9 showed spherical morphology. Nasal inserts had assay of drug content of (82.5 ± 2.5% to 103.94 ± 3.94%), Q15min% of (89.9 ± 6.4% to 100%) and Muco-adhesion strength of (3510.5 ± 140.21 to 9319.5 ± 39.425). DSC results of S4 and S8 showed compatibility of (ATM) with the other excipients. S8 and S4 also showed higher trans-nasal permeation to the brain with brain targeting efficiency of (211.3% and 177.42%, respectively) and drug transport percentages of (52.7% and 43.64%, respectively). To conclude, lyophilized nasal inserts of (ATM-SLNs) enhanced (ATM) trans-nasal drug targeting permeation and brain targeting efficiency.
RESUMO
A PEGylated Tween 80-functionalized chitosan-lipidic (PEG-T-Chito-Lip) nano-vesicular hybrid was developed for intranasal administration as an alternative delivery route to help improve the poor oral bioavailability of BCS class-III model/antiemetic (metoclopramide hydrochloride; MTC). The influence of varying levels of chitosan, cholesterol, PEG 600, and Tween 80 on the stability/release parameters of the formulated nanovesicles was optimized using Draper-Lin Design. Two optimized formulations (Opti-Max and Opti-Min) with both maximized and minimized MTC-release goals, were predicted, characterized, and proved their vesicular outline via light/electron microscopy, along with the mutual prompt/extended in-vitro release patterns. The dual-optimized MTC-loaded PEG-T-Chito-Lip nanovesicles were loaded in intranasal in-situ gel (ISG) and further underwent in-vivo pharmacokinetics/nose-to-brain delivery valuation on Sprague-Dawley rats. The absorption profiles in plasma (plasma-AUC0-∞) of the intranasal dual-optimized MTC-loaded nano-vesicular ISG formulation in pretreated rats were 2.95-fold and 1.64-fold more than rats pretreated with orally administered MTC and intranasally administered raw MTC-loaded ISG formulation, respectively. Interestingly, the brain-AUC0-∞ of the intranasal dual-optimized MTC-loaded ISG was 10 and 3 times more than brain-AUC0-∞ of the MTC-oral tablet and the intranasal raw MTC-loaded ISG, respectively. It was also revealed that the intranasal dual-optimized ISG significantly had the lowest liver-AUC0-∞ (862.19 ng.g-1.h-1) versus the MTC-oral tablet (5732.17 ng.g-1.h-1) and the intranasal raw MTC-loaded ISG (1799.69 ng.g-1.h-1). The brain/blood ratio profile for the intranasal dual-optimized ISG was significantly enhanced over all other MTC formulations (P < 0.05). Moreover, the 198.55% drug targeting efficiency, 75.26% nose-to-brain direct transport percentage, and 4.06 drug targeting index of the dual-optimized formulation were significantly higher than those of the raw MTC-loaded ISG formulation. The performance of the dual-optimized PEG-T-Chito-Lip nano-vesicular hybrids for intranasal administration evidenced MTC-improved bioavailability, circumvented hepatic metabolism, and enhanced brain targetability, with increased potentiality in heightening the convenience and compliance for patients.
Assuntos
Quitosana , Metoclopramida , Ratos , Animais , Metoclopramida/metabolismo , Polissorbatos , Quitosana/metabolismo , Disponibilidade Biológica , Ratos Sprague-Dawley , Sistemas de Liberação de Medicamentos , Administração Intranasal , Encéfalo/metabolismo , Lipídeos , Portadores de Fármacos/metabolismoRESUMO
This study aimed to formulate and evaluate a floating raft system for the co-delivery of etoricoxib (ETO) and famotidine (FAM) using a combination of glucomannan with natural/semi-synthetic polysaccharides. Formulation variables affect gelation lag time (GLT), floating lag time (FLT), and release percentage of drugs after 1-8 h, Stability, and viscosity parameters were evaluated. In vivo X-ray studies, followed by the pharmacokinetic study, were performed on human volunteers. Formulations exhibited pseudoplastic behavior for ease of swallowing. The optimum raft system (ORS) comprised 1% Na alginate, 0.1% Low Methoxyl (LM) pectin, 0.8% Konjac glucomannan (KGL), 1% Precirol, and 1% CaCO3. ORS exhibited rapid GLT and FLT (around 42 and 8 sec respectively) in 0.1 N HCl as well as controlled release of ETO (15% in 1 h and 82% in 8 h) and FAM (29% in 1 h and 85% in 8 h). Formulation stability with the absence of any drug-excipient interactions was observed. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. Compared with marketed products, ORS showed superior relative bioavailability for both drugs. These findings revealed the successful preparation of a promising raft system with improved dual drug delivery.