Percentage Entrapment Efficiency Research Articles

Dasatinib loaded mucoadhesive lecithin-chitosan hybrid nanoparticles for its augmented oral delivery, in-vitro efficacy and safety

Dasatinib (DAS) is an oral tyrosine kinase inhibitor; however, its efficacy is significantly subsided by its low oral bioavailability. The present research aimed to improve DAS’s oral delivery and efficacy in triple-negative breast cancer by fabricating its mucoadhesive lecithin-chitosan hybrid nanoparticles (DAS-L/CS-NPs). DAS-L/CS-NPs were optimized using Box-Behnken design which showed mean particle size and percent entrapment efficiency of 179.7 ± 5.42 nm and 64.65 ± 0.06 %, respectively. DAS-L/CS-NPs demonstrated sustained release profile in different release media up to 48 h and showed 10 times higher apparent permeability coefficient and flux than free DAS suspension. The binding of DAS-L/CS-NPs to the mucus layer was demonstrated via ex-vivo mucoadhesion study and change in absorbance using turbidimetry. In cell culture studies, DAS-L/CS-NPs revealed a 4.14-fold decrease in IC50, significantly higher cellular uptake and mitochondrial membrane depolarization, 3.82-fold increased reactive oxygen species generation and 2.10-fold enhanced apoptosis in MDA-MB-231 cells than free DAS. In in-vivo pharmacokinetic assessment, DAS-L/CS-NPs showed a 5.08-fold and 3.74-fold rise in AUC (0-t) and Cmax than free DAS suspension, respectively. An acute toxicity study revealed a good safety profile of DAS-L/CS-NPs. In a nutshell, proposed hybrid nanoparticles are promising carriers for improved oral delivery of poorly water-soluble drugs.

Preparation and evaluation of a niosomal delivery system containing G. mangostana extract and study of its anti-Acanthamoeba activity.

Garcinia mangostana extract (GME) has severe pharmacokinetic deficiencies and is made up of a variety of bioactive components. GME has proven its anti-Acanthamoeba effectiveness. In this investigation, a GME-loaded niosome was developed to increase its potential therapeutic efficacy. A GME-loaded niosome was prepared by encapsulation in a mixture of span60, cholesterol, and chloroform by the thin film hydration method. The vesicle size, zeta potential, percentage of entrapment efficiency, and stability of GME-loaded niosomes were investigated. The values for GME-loaded niosome size and zeta potential were 404.23 ± 4.59 and -32.03 ± 0.95, respectively. The delivery system enhanced the anti-Acanthamoeba activity, which possessed MIC values of 0.25-4 mg mL-1. In addition, the niosomal formulation decreased the toxicity of GME by 16 times. GME-loaded niosome must be stored at 4 °C, as the quantity of remaining GME encapsulated is greater at this temperature than at room temperature. SEM revealed the damage to the cell membrane caused by trophozoites and cysts, which led to dead cells. In light of the above, it was found that GME-loaded niosomes had better anti-Acanthamoeba activity. The study suggested that GME-loaded niosomes could be used as an alternative to Acanthamoeba's therapeutic effects.

Advanced psoriasis treatment: Development and optimization of resorcinol-loaded nanoemulgel with lavender oil

<p>Psoriasis, a long-term autoimmune illness, affects 2%–5% of people worldwide. Drugs from BCS class II that are commonly used to treat psoriasis include resorcinol, which presents burning feelings and itchiness as adverse effects. To minimize adverse effects and increase the effectiveness of treatment, a topical nanoemulgel was developed in the current research. A resorcinol-loaded nanoemulgel was developed using the nanoemulsion technique, and the Design Expert<sup>®</sup> CCD method was used for optimization. Particle size (PS), zeta potential (ZP), and percentage of entrapment efficiency (EE%) served as the foundation for the optimization. The morphology, chemical interactions between excipients, crystallinity, and thermal behavior of the optimized resorcinol-loaded nanoemulgel were examined by TEM, FTIR, and XRD physicochemical studies. The resorcinol-loaded nanoemulgel was successfully loaded and characterized. For the in vitro release, the dialysis bag technique was employed. The ideal PS, PDI, and ZP values for the optimized resorcinol-loaded nanoemulgel were 31.32 ± 3.1 nm, 0.24 ± 0.005, and −10.6 ± 1.0 mV, respectively. The FTIR data revealed that no chemical interactions were observed between the components of resorcinol-loaded nanoemulgel, while the TEM results supported the spherical shape. The in vitro study confirmed a sustained release of resorcinol-loaded nanoemulgel.</p>

Nose to brain delivery of flurbiprofen from a solid lipid nanoparticles-based thermosensitive in-situ gel.

Flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), has selective amyloid-lowering characteristics and can be utilized for Alzheimer's disease treatment. Oral flurbiprofen has poor brain bioavailability and high dose-related gastrointestinal adverse effects. To overcome these issues, the study aimed to formulate intranasal flurbiprofen solid lipid nanoparticles (SLN) based thermosensitive in-situ gel. SLN were formulated by the High-speed homogenization method. A 23 factorial design technique was utilized for optimization, wherein the influence of two independent variables, critical process parameters (X1 = surfactant concentration, X2 = D:L ratio) on critical quality attributes (Y1 = particle size, Y2=Percent Drug Loading, Y3=Percent Entrapment Efficiency) was ascertained at three distinct levels. The optimized SLN were then prepared into an SLN-based intranasal thermosensitive in-situ gel with Poloxamer 188 P (1.2% w/v) and Poloxamer 407 P (18% w/v). The in-vitro flurbiprofen release study demonstrated a 100% release of flurbiprofen from the SLN-based thermosensitive in-situ gel at 6 h. The ex-vivo flurbiprofen release study revealed a complete release of flurbiprofen from the SLN-based thermosensitive in-situ gel at 8 h. In the in-vivo tests, the in-situ gel (2 mg/kg) administered intranasally in rats demonstrated nearly three times greater brain bioavailability (Cmax = 490.3 ng/ml) than the oral marketed formulation of flurbiprofen, Ansaid® (10 mg/kg) (Cmax = 145.1 ng/ml). The plasma concentration obtained with intranasal in-situ gel (Cmax = 2.5 μg/ml) was lower than the oral marketed formulation (Cmax = 3.4 μg/ml). The time necessary to establish the maximal flurbiprofen concentration (Tmax) in the brain was 2 and 0.5 h for oral and intranasal formulations, respectively. Hence, the intranasal formulation could achieve maximal drug concentration in the brain in less time. Thus, flurbiprofen SLN-based thermosensitive in-situ gel can be a potential encouraging safe, non-invasive, and efficacious replacement to oral formulations for achieving direct brain targeting through nose-to-brain drug delivery, thereby treating neuroinflammatory conditions like Alzheimer's disease.

Analytical quality by design approach to develop an eco-friendly RP-HPLC method for estimation of irbesartan in chitosan polymeric nanoparticles: forced degradation studies and assessment of in vitro release mathematical modelling.

Irbesartan is an angiotensin converting enzyme blocker, primarily utilized for the management of hypertension and the mitigation of diabetic nephropathy progression. The present study introduces rapid, robust and environmentally sustainable reverse phase high performance liquid chromatography (RP-HPLC) validated under the analytical quality by design (AQbD) framework according to ICH guidelines. Utilizing a central composite design, the method's systemic optimization was achieved, ensuring reproducibility and accuracy. Chromatographic separation was accomplished utilizing an ethanol and sodium acetate buffer (60 : 40 v/v) isocratic mobile phase system on a zorbax sb C18 column, with a flow rate of at 0.6 mL min-1. Studies on forced degradation outlined stability of irbesartan and its degradation processes, enhancing our understanding of its chemical robustness under varied conditions. Complementing the green chemistry paradigm, the method's environmental impact was critically assessed, affirming its alignment with sustainability objectives. The validated method proved pivotal in determining the percent entrapment and loading efficiency of the formulated nanoparticles and holds potential for application in biological matrices. Furthermore, the encapsulation of IRB within chitosan nanoparticles was explored to assess release kinetics and enhance bioavailability. This study not only advances the analytical sciences by merging eco-friendly practices with method development but also broadens the applicative landscape of HPLC methodologies in drug delivery research.

Proniosomal gel mediated transdermal delivery of Donepezil HCl: Development and in vitro characterization

The aim of this research was to study the potential of proniosomal gel for transdermal delivery. Donepezil HCl loaded proniosomal gels were prepared by the coacervation phase separation method using different nonionic surfactants (spans and tweens). The prepared Donepezil HCl proniosomal gels were evaluated for various parameters such as particle size (PS), drug entrapment efficiency percentage (EE %), and in vitro drug release. Donepezil HCl loaded proniosomal gel was prepared successfully by coacervation phase separation method. The prepared proniosomal gel exhibited desired entrapment efficiency and Particle size. It was found that B2 which chosen as a best formula according to entrapment efficiency, Particle size, and in vitro release study. It was found that B2 which contains high concentration of span 60 is the most appropriate surfactant for the preparation of proniosomes. In vitro release studies proved that the prepared proniosomal gel contains Donepezil HCl considered to be a successful topical transdermal drug delivery system and provide a sustained release of encapsulated drug. Furthermore, there was no significant change in EE % and PS of Donepezil HCl proniosomal gel after storage for 6 months.

Quality by Design Assisted Development of Luliconazole Transethosomes in Gel for the Management of Candida albicans Infection.

The objective of this study was to develop and evaluate a novel vesicular formulation of luliconazole (LUL) for the management of Candida albicans infection through a topical route. LUL-loaded transethosomes (LUL-TE) were prepared by the film hydration method and various independent and dependent variables were optimized using the Box-Behnken design. Selected critical material attributes were the content of phospholipids (X1), concentration of ethanol (X2), and amount of sodium cholate (X3). Formulated LUL-TE were characterized for percent entrapment efficiency, percent drug loading, vesicle size, and polydispersity index (PDI) and were incorporated into the carbomer gel base and further evaluated for gel characterizations. The prepared transethosomal gel (LUL-TE-CHG) was evaluated for pH, spreadability, viscosity, antifungal activity, and in vitro study. From the observed results, it was evident that the prepared LUL-TE-CHG was in the desired pH (6.2 ± 0.45), spreadability [8.3 ± 0.42 g/(cm·s)], viscosity (236.1-19.2.26 mPa·s), nanovesicle size (252 ± 9.82), entrapment efficiency (85% ± 5.24%), zeta potential (-34.05 ± 3.52 mV), and PDI (0.233 ± 0.002). The zone of inhibition results suggested that the LUL-TE-CHG formulation has the highest antifungal activity, that is, 5.83 ± 0.15 mm3. The in vitro results showed that drug release within 2 h was 18.1% ± 2.0% and after that sustained release action, 83.2% ± 1.7% within 8 h. Finally, to confirm the therapeutic efficacy of the developed formulation, fungal infection was induced by using C. albicans in Wistar rats. In vivo, skin irritation study and histopathology studies were performed in the disease-induced model. Animal experiments revealed that LUL-TE-CHG has significantly improved the diseased condition in Wistar rats. The results observed from the skin permeation and skin deposition profile ensure that the prepared novel LUL-loaded TE system had a higher permeation rate and increased retention time compared with LUL-CHG. The hydrogel incorporated with LUL could be a novel approach with safe and effective fungal treatment.

Competitive inhibition of nicotine acetylcholine receptors using microneedles of nicotine and varenicline for smoking withdrawal therapy

Current strategies for smoking withdrawal conditions involve monotherapy of nicotine and combinational therapy of nicotine with varenicline or bupropion as per the CDC and FDA. The available dosage forms for nicotine are patches, gums, inhalers and nasal sprays, bupropion and varenicline are available in tablet form. This research work focused on developing a microneedle delivery system to deliver combination drug for overcoming the obstacles encountered by oral route of administration of varenicline such as severe side effects (mood swings, agitation, depressed behaviour, seizures, etc), and nicotine therapy challenges such as short half-life, repeated dosing, nausea, and vomiting. The nanoparticles of nicotine prepared by nanoprecipitation method showed particle size PTZ (356.6 ± 65.98), percentage entrapment efficiency (35.55 % ± 0.007), in-vitro drug release (47.89 % ± 0.7) for 72 h. Microneedles showed height (600 μm), width (350 μm), and tip diameter (10 μm). The nanoparticles encapsulated in microneedles showed in-vitro sustained delivery of nicotine (67.00 % ± 4.92) and varenicline (79.78 % ± 1.09) in 48 h. Nicotine released in a sustained manner attaches to the nicotine acetylcholine receptors (nAchR) to release dopamine for controlling the withdrawal challenges such as anxiety, irritability, cravings, disturbed sleep pattern, etc. The varenicline released from microneedles binds to the nAchR and inhibits dopamine release responsible for the euphoric effect induced by nicotine, and thus assists in curbing the nicotine withdrawal symptoms. This combination microneedle system offers prolonged treatment in a single application for smoking withdrawal conditions wherein patients are not in stage of oral dosing because of repeated dosing resulting in adverse effects like seizures, hypertension, sleep disturbances, insomnia, and nausea.

Development and evaluation of a protease inhibitor antiretroviral drug-loaded carbon nanotube delivery system for enhanced efficacy in HIV treatment

The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels.In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems.

Development and In-Vitro Evaluation of Eugenol-Based Nanostructured Lipid Carriers for Effectual Topical Treatment Against C. albicans

The main objective of the experiment is to develop and evaluate hydrogel-bearing nanostructured lipid carriers (NLCs) loaded with ketoconazole (KTZ) for the effective treatment of candidiasis. The eugenol was used as a liquid lipid (excipient) for the development of KTZ-loaded NLCs and was explored for anti-fungal effect. The production of NLCs involves high energy processes to generate spherical, uniform particles, having a higher percentage of entrapment efficiency (%EE) for KTZ with 89.83 ± 2.31 %. The data from differential scanning calorimeter (DSC), powder x-ray diffraction (PXRD), and attenuated total reflectance (ATR) demonstrated the KTZ dispersion in NLCs. The NLCs loaded hydrogel possessed optimum spreadability and exhibited shear thinning behavior, indicating the ease of application of the final formulation. The 6.41-fold higher transdermal flux (Jss) was governed for KTZ from KTZ-NLC than coarse-KTZ, which explains the usefulness of NLCs. The KTZ-NLCs exhibited significant 2.58 and 6.35-fold higher retention in the stratum corneum and viable epidermis of the skin. The cell cytotoxicity studies using human dermal fibroblast cell (HDFS) lines depicted the usefulness of NLCs in reducing cell toxicities for KTZ. The KTZ-NLCs were found to inhibit planktonic growth and hyphal transition and showed a larger zone of inhibition against C. albicans strains with a MIC-50 value of 0.39 μg/mL. The antibiofilm activity of KTZ-NLCs at lower concentrations, in contrast to plain KTZ, explained the interaction of developed NLCs with fungal membranes. The overall results depicted the effectiveness of the loading KTZ in the lipid matrix to achieve antifungal activity against C. albicans.

Exploiting response surface D-optimal design study for preparation and optimization of spanlastics loaded with miconazole nitrate as a model antifungal drug for topical application

PurposeSkin fungal infections are widely spreading worldwide and are considered a main cause of skin, mucous membranes, and systemic diseases. In an approach to enhance the topical delivery of miconazole nitrate (MZN) as a poorly permeable antifungal agent, spanlastics nanocarriers as a type of elastic vesicles were adopted in the current work.MethodsMZN spanlastics were prepared and optimized according to a D-optimal response surface design to investigate the influence of formulation variables, edge activator (EA) percentage, EA type on particle size (PS), and drug entrapment efficiency percentage (% EE) as dependent variables. The spanlastics optimized formula (F7) was further assessed for its elasticity and physico-pharmaceutical properties before being incorporated into a gel. The F7 gel formula was also examined for its physical properties, in vitro release, in vitro antifungal activity against Candida albicans (ATCC® 10231), and ex vivo skin deposition studies. The results of the F7 gel formula were compared to the F7 aqueous dispersion.ResultsThe D-optimal design revealed that F7, developed using Tween 60 as EA and Span 60 at a weight ratio 2:8, is the optimized formula. F7 was an elastic, spherical, non-aggregated vesicle with an average PS of 210 nm and a drug entrapment efficiency of 90%. The drug was present in an amorphous form within the vesicles. The gel form of F7 showed a prolonged drug release behavior relative to the solution form, where 75% of the drug was released over 10 h for the former and 5 h for the latter. The antifungal study revealed a significant (p < 0.05) increase in the zone of inhibition of Candida albicans (ATCC® 10231) demonstrated by spanlastics compared to MZN suspension at the same concentration level. MZN suspension showed cytotoxic activity at a concentration of 20 μg/mL and above; the incorporation of the drug in spanlastics dispersion or gel form increased the cell viability percentage. The skin deposition studies showed that F7 deposition in the dermal layer, where deep skin infections occur, is 164-folds that of the plain drug.ConclusionsThe results confirm the potential application of MZN-spanlastics to treat deeply seated skin fungal infections.

QbD-driven RP-HPLC method for novel chemo-herbal combination, in-silico, force degradation studies, and characterization of dual drug-loaded polymeric and lipidic nanocarriers

BackgroundIn cancer therapies, chemo-herbal combinations are receiving increased attention. A multiple tyrosine kinase inhibitor, lenvatinib (LTB) is beneficial in treating thyroid, lung, endometrial, and liver cancers. An isoflavone called biochanin A (BCA) is well known for its diverse biological properties that have been studied to potentiate the anti-cancer potential and lower the normal cell toxicities of other therapeutics. LTB and BCA can be combined for cancer treatment and may increase their therapeutic potential at lower doses. In brief, the quality by design (QbD)-driven RP-HPLC method was developed, validated, and utilized for applications employing the study of forced degradants and the successful development of LTB and BCA co-loaded nanocarriers.ResultsThe RP-HPLC method employed Box–Behnken design with peak resolution 6.70 ± 0.006, tailing factor 1.06 ± 0.05 for BCA and 1.17 ± 0.021 for LTB, and theoretical plates number > 2000. RP-HPLC applications utilized the investigation of a total of 41.17% and 70.58% degradants for LTB and BCA in contrast to in-silico predicted studies using Zeneth software. The poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) were formed with particle size 185.3 ± 12.3 nm, zeta potential − 13.3 ± 0.35 mV, and percentage entrapment efficiency (%EE) for the LTB and BCA 53.64 ± 4.81% and 61.29 ± 4.67%, respectively. However, the developed Cubosomes (CBs) exhibited 182.4 ± 16.3 nm aerodynamic particle size, − 10.8 ± 0.39 mV zeta potential, and % EE for LTB and BCA 55.62 ± 7.73% and 72.88 ± 5.52%, respectively. The percentage drug loading (%DL) of LTB and BCA from PLGA NPs was found to be 3.7 ± 0.46% and 4.63 ± 0.48%, whereas CBs exhibited higher % DL for BCA (5.42 ± 1.10%) and LTB (4.43 ± 0.77%).ConclusionThe RP-HPLC method was developed and validated according to ICH and USP guidelines. In-vitro and in-silico forced degradation studies are evident to quantify the type of degradant and its exact mechanism of degradation. In-silico toxicity assessment for LTB, BCA, and their degradants explains the necessity of conducting degradation studies during drug development. Finally, the applications of the developed RP-HPLC method explain the usefulness of analytical methods in the development of chemo-herbal drug nanocarriers (polymeric and lipidic).Graphical abstract

FORMULATION OF VITEX NEGUNDO ETHOSOMAL LOADED TOPICAL HERBAL GEL AND ITS EVALUATION FOR ARTHRITIS TREATMENT

The current research aims to develop and test a system of vesicular drug carriers for topical drug administration of Vitex negundo Linn. to provide sustained drug delivery. The ethosomes of V. negundo Linn. were produced using thin-film hydration, and their in vitro drug release profiles, size, drug content, and other characteristics were examined. To attain the desired results, for drug release and entrapment effectiveness, the composition of lecithin and ethanol was changed to form ethosomes. The ethosomal size of the vesicle of the optimized formulation batch was measured to be the units 13.47 nm with -3.97 mV as zeta potential. The percent drug release of ethosomal gel was 83.24 %, and the percent entrapment efficiency was 89.40 %. The formation of spherically shaped vesicles was confirmed by optical and scanning electron microscopy observations. It was observed that as the ethanol concentration increased, the formulation’s in vitro profile for drug release increase, and lipid concentration decreases.

Transferrin functionalized poloxamer-chitosan nanoparticles of metformin: physicochemical characterization, in-vitro, and Ex-vivo studies

Object We report the preparation, characterization, and in-vitro therapeutic evaluation of Metformin-Loaded, Transferrin-Poloxamer-Functionalized Chitosan Nanoparticles (TPMC-NPs) for their repurposing in Alzheimer’s disease (AD). Significance Usefulness of this work to establish the repurposing of metformin for the treatment of AD. Methods The TPMC-NPs were prepared by ionic gelation method using sodium tripolyphosphate. The modification and functionalization were confirmed by FTIR and 1H-NMR spectroscopy. The physicochemical characterization was performed using DLS, FTIR,1H-NMR, CD spectroscopy, SEM, DSC, PXRD, HR-TEM, and hot-stage microscopy. Results The size, PDI, percent entrapment efficiency, and percent drug loading of TPMC-NPs were found to be 287.4 ± 9.5, 0.273 ± 0.067, 81.15 ± 7.17%, 11.75%±8.21%, respectively. Electron microscope analysis revealed smooth and spherical morphology. The transferrin conjugation efficiency was found to be 46% by the BCA method. CD spectroscopy confirmed no significant loss of the secondary structure of transferrin after conjugation. PXRD data indicated the amorphous nature of the TPMC-NPs. Hot-stage microscopy and DSC confirmed the thermal stability of TPMC-NPs. The in-vitro drug release showed a sustained release at pH 7.4. The DPPH assay displayed 80% antioxidant activity of TPMC-NPs in comparison with metformin and blank NPs. The in-vitro cytotoxicity assay revealed 69.60% viable SH- SY5Y cells at 100 µg/mL of TPMC NPs. The ex-vivo nasal ciliotoxicity and mucoadhesion studies showed no significant toxicity, and 98.16% adhesion, respectively. The nasal permeability study showed the release of metformin within 30 min from TPMC-NPs. Conclusion The obtained results suggested the usefulness of TPMC-NPs in the treatment of AD via the intranasal route.

Impact of miconazole nitrate ferrying cationic and anionic nanoemulsion and gels on permeation profiles of across EpiDerm, artificial membrane, and skin: Instrumental evidences

Based on our previous report, the study was extended to investigate the impact of miconazole nitrate (MCN) loaded cationic/anionic nanoemulsions and nanoemulsion gels on permeation behaviour across artificial-membrane, EpiDerm, and rat skin. Nanoemulsions and gels were evaluated for size, charge, viscosity, size-distribution, pH, and percent entrapment efficiency (%EE). In vitro drug diffusion across artificial membrane and EpiDerm were conducted to get diffusion coefficients. Permeation profiles were studied using rat skin to investigate mechanistic insight of formulated mediated permeation followed by CLSM (confocal laser scanning microscopy), SEM (scanning electron microscopy), AFM (atomic force microscopy), and irritation studies. Results showed that MCNE11-Rh (probed cationic nanoemulsion at pH ∼ 7.2) and MNE11-Rh (probed anionic nanoemulsion at pH ∼ 7.2) showed size values of 158 nm and 145 nm, respectively whereas MCNE11-GR (probed cationic nanoemulsion gel at pH ∼ 6.8) and MNE11-GR (probed anionic nanoemulsion gel at pH ∼ 6.8) exhibited size values 257 nm and 243 nm, respectively. The %EE values were found to be as 91.5 % and 89.6 % for MCNE11-Rh and MNE11-Rh, respectively. The gels (∼6000 cP) elicited relatively high viscosity than nanoemulsions (∼3300 – 3500 cP). MCNE11-GR showed the highest values of permeation flux, diffusion rate, diffusion coefficient (D), and permeation coefficient (P) across artificial membrane, EpiDerm, and rat skin which may be attributed to three potential factors (cationic charge, composition, and hydration by the hydrophilic gel) working in tandem. Transepidermal water loss (TEWL) by the MCNE11-GR was maximum (14.4 g/m2h) than control (6.1 g/m2h) indicating augmented interaction of MCNE11-Rh with skin components. Conclusively, cationic nanoemulsion gel was promising carrier for enhanced permeation and the drug access to the dermal region to treat deep seated fungal infections.

Acitretin-loaded nanoethosomal gel for the treatment of psoriasis: Formulation, optimization, in vitro, and in vivo assessment

Acitretin (ACT) is a second-generation systemic retinoid used to treat severe psoriasis. However, its poor aqueous solubility and systemic adverse effects make it impractical for oral administration. The primary objective of this research is to prepare, optimize, and evaluate a nanogel consisting of acitretin-loaded ethosomes (ACT-ETH) for its anti-psoriatic potential. A 32 full factorial design was employed for optimization. Thin-film hydration was adopted to prepare ACT-ETH, and then their physicochemical characteristics were tested. The optimized ACT-ETH was converted into a carbopol gel and then evaluated for cytotoxicity, skin irritation, and anti-psoriatic properties. The vesicle size, zeta potential (ZP), and percent entrapment efficiency (% EE) of the optimal ACT-ETH are 147 ± 2.15 nm, −11.5 ± 0.25 mV, and 90.70 ± 0.89%, respectively. The fluorescence microscopy study has shown that ethosomes may go deeper into the skin layers. Compared to plain gel, ACT-ETH gel greatly increased skin permeability and deposition in the ex-vivo skin permeation and deposition tests. The in vitro cytotoxicity investigation revealed that the cytotoxicity of ACT against normal cells (L-929) was significantly reduced by ACT-ETH gel compared to plain ACT gel. The skin irritation study proved that ACT-ETH gel was well tolerated and safe for use on the skin. The in vivo anti-psoriatic study showed that using ACT-ETH gel to treat psoriasis on the skin led to a significant improvement in the therapeutic response. Based on these results, ACT-ETH gel has the potential to increase the topical anti-psoriatic action of ACT by mitigating its known drawbacks.

Aceclofenac loaded microspheres: Formulation and evaluation of novel preprogrammed drug delivery for the treatment of arthritis

Arthritis is a widespread joint disorder globally, the patient completely dependent on NSAIDs which are administered after a fixed interval to subside the pain. This work aims to establish a preprogrammed drug delivery system of aceclofenac with a predetermined lag time for the treatment of arthritis. This new preprogrammed formulation microsphere reduces the time-dependent dose administration as it steadily releases the drug in the blood circulation reducing side effects and increasing patient compliance. Aceclofenac (ACF) loaded polymer microspheres were prepared by a new emulsification and crosslinking method using glutaraldehyde as cross-linking agent. Microspheres were prepared in 6 batches using different polymers like sodium alginate, guar gum and chitosan, alone, as well as in combinations. The type and quantity of polymers were changed in every batch while the amount of aceclofenac was unvarying. The microspheres were then evaluated for the particle size, drug content, percentage yield, percentage entrapment efficiency and percentage drug release followed by noting the lag time. The microsphere loaded with aceclofenac were formulated and evaluated, the result showed that all the preparations showed a good lag time (2–3 ​h), but chitosan (alone) gave the highest lag time, which fulfills the aim of pre-programmed drug delivery system. Preprogrammed drug release has been achieved from the microspheres over a period of 0–7 ​h, consistent with the demand for chronotherapeutic drug delivery for the treatment of arthritis. The major signification of the preparation technique includes short processing time and the lack of exposure of the ingredients to high temperatures. Aceclofenac-loaded microspheres offer a promising avenue for arthritis treatment, ensuring sustained drug release. Their potential clinical implications include enhanced therapeutic efficacy, reduced side effects, and improved patient compliance. Future directions may involve personalized formulations, targeted delivery systems, and exploring applications beyond arthritis, expanding the scope of this innovative drug delivery approach.

Investigating the Correlation Between Drug Physical Properties and Physical Characteristics and Drug Entrapment Efficiencies of Chitosan-TPP Nanoparticles

Chitosan nanoparticles (NPs) have been the subject of intensive research. This study aimed to determine how different drug characteristics such as molecular weights, drug solubility in the processing medium, and drug ionization/charge state affected chitosan NPs particularly their percentage entrapment efficiency (% EE) and mean hydrodynamic diameters (MHDs). Drugs with varying molecular weights but of similar aqueous solubilities were chosen and were dissolved in a 2% chitosan-acetic acid solution. Chitosan NPs were formed using by ionic gelation technique using sodium tripolyphosphate (TPP) at specific concentration and volume ratios of chitosan to TPP. NPs containing Enalapril and Paracetamol displayed better short-term stability in terms of MHDs. A direct relationship between MHDs of NPs and chitosan concentrations was found. In comparison, at both low and high admixed drug concentrations and at high chitosan concentration, larger NPs sizes were associated with the lower molecular weight drug (Paracetamol). However, the study did not demonstrate a direct relationship between NPs characteristics such as MHDs and drugs molecular weights. The ZP of Paracetamol-loaded NPs was lowest at high drug concentrations at all chitosan concentrations compared to other drugs-loaded NPs. When compared to drugs with high and low molecular weights, medium molecular weight Atenolol showed the highest % EE. This clearly indicated that there was no direct correlation between drug molecular weight and % EE, but rather other factors influenced on % EE. Nevertheless, an inverse linear relationship with high correlation coefficients was only found when % EE was plotted against each drug molecular weight divided by the ratio of drugs solubilities in acetic acid to their employed concentrations, however the correlation was inconsistent between drugs of varying molecular weights.

IMPLICATION OF CENTRAL COMPOSITE DESIGN IN THE DEVELOPMENT OF SIMVASTATIN-LOADED NANOSPONGES

Objective: The present study’s objective was to apply a central composite design to develop the simvastatin-loaded nanosponge formulation to improve its oral bioavailability. Methods: With the help of a design expert (State-Ease version 13.0.1), a central composite design was selected for the formulation of simvastatin-loaded nanosponges by using a defined concentration of Eudragit L-100 (X1) and PVA (X2) as independent variables and particle size (Y1), percent (%) entrapment efficiency (EE) (Y2), in vitro drug release (Y3) as dependent variables. Fourteen (SF1-SF14) formulations were prepared using the emulsion solvent evaporation and evaluated for surface morphology, particle size, drug-excipient compatibility, %EE, and % drug release. The optimized model (SF14) obtained from a design expert was evaluated for in vivo pharmacokinetics in animal models. Results: SF14 was formulated and evaluated for morphology (shape and size) of the particle, % EE, in vitro % drug release, and its kinetics. The formulation showed particle size of 163±0.45 nm, 80.54 %±0.57 of EE, and 97.13%±0.38 of drug release at 8h. The release kinetics followed the zero-order and Higuchi mechanisms with non-fiction diffusion. In vivo results showed Cmax, Tmax, AUC0-t, AUC0-α, and MRT0-α for nanosponges were 0.175 µg/ml, 6 h, 1.561 µg/mlh, 1.755 µg/mlh, 11.77 h, respectively. Conclusion: The results indicated a significant increase in the bioavailability of the drug in nanosponges compared with standard drugs. The experimentally designed nanosponge formulations have been successfully developed, and evaluated parameters show that the nanosponge formulation of Simvastatin is a promising delivery through the oral route.

Preparation, Optimization, Characterization, and Evaluation of Rosuvastatin Loaded Solid Lipid Nanoparticles Using Quality by Design Approach

The present research work aims to prepare and characterize solid lipid nanoparticles (SLN) containing rosuvastatin calcium (RT). We aim to use a novel microwave-assisted microemulsion technique to produce Rosuvastatin-loaded SLN. The characterization of the optimized formulation of RTSLN was carried out by employing Fourier-transformed infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC) studies showed that there was no chemical interaction between drug (Rosuvastatin Calcium) and lipid (GMS), XRD indicated the amorphization of RTSLN formulation. In contrast, scanning electron microscopy (SEM) studies indicated that Rosuvastatin Calcium loaded SLNs are spherical, discrete, and homogeneous. In vitro and ex vivo drug release studies showed sustained drug release action. The effect of dependent variables such as entrapment efficiency (EE), particle size, and independent variables like % GMS and Poloxamer 407 was observed using a 32-factorial design approach. Optimized formulation was selected based on the 2D &amp; 3D counter and surface response plots. The prepared formulations show percentage entrapment efficiency within the range of 53 to 78%, particle size in the 254.2 to 863.4 nm, and in vitro drug release was found to be 79.8%. Also, ex vivo absorption was 76.7 % for 8 hours. The need of the research work is to use microwave energy over conventional heating to prepare SLNs also helps to resolve problems associated with conventional colloidal drug delivery systems, which leads to improved drug bioavailability.