Percentage Entrapment Efficiency Research Articles

Rutin loaded bilosomes for enhancing the oral activity and nephroprotective effects of rutin in potassium dichromate induced acute nephrotoxicity in rats

Rutin, a flavone glycoside, has shown to have a significant beneficial kidney protection effect in drug-induced nephropathy. However, its poor solubility and low oral bioavailability have limited its pharmacological applications. This study aimed at formulating rutin-loaded bilosomes to enhance the renal protective effect of rutin for oral application. Rutin-loaded bilosomes were developed using thin-film hydration technique. The prepared formulations were characterized by entrapment efficiency percentage (EE%), vesicular size (VS) and zeta potential (ZP) measurement. The developed formula exhibited moderate EE%, ranging from 20.02 ± 2.85 to 48.57 ± 3.57%, suitable VS results that ranged from 502.1 ± 36 to 665.1 ± 45 nm and high ZP values (≤ -41.4 ± 7.27 mV). Transmission electron microscopy revealed the spherical shape of the developed bilosomes. The in-vitro release study revealed prolonged release of rutin from bilosomes, relative to free drug. F2, prepared using the molar ratio span 60: cholesterol: sodium cholate 1:1:0.5, was selected for further investigations as it showed the highest EE%, smallest VS, optimum ZP, and persistent release profile. In-vivo studies were performed on drug-induced nephropathy in rats. Acute renal failure was induced using a single dose of potassium dichromate (PDC; 15 mg/kg; i.p). The selected formulation, F2, alleviated kidney dysfunction, oxidative stress and inflammation via decreasing MDA, TNF-α and TGF-β and increasing GSH. In addition, F2 promoted Akt/PI3K activation against PDC-induced acute renal failure. Histopathology results came in accordance with in-vivo results. Thus, bilosomes could be considered a potential delivery system for enhancing the oral delivery and kidney protection activity of rutin.

Formulation and Evaluation of Glipizide-loaded Mucoadhesive Microparticle Using Salvia hispanica Seeds Mucilage as Co-polymer

Aims: Chia seed (Salvia hispanica L.) gum is a mucoadhesive, biodegradable polymer with sustained release properties. Objective: The objective of this study was to compare different formulations of glipizide-loaded microparticles using chia seed mucilage and sodium alginate, focusing on sustained release and mucoadhesive properties. Background: The present study aimed to comparatively evaluate various eco-friendly formulations of glipizide-loaded microparticles prepared using chia seed mucilage and sodium alginate. Materials and Methods: Gum was extracted from chia seeds and lyophilized, and preformulation studies were performed according to established protocols. Microparticles were formulated using the ionic gelation method, with sodium alginate as a copolymer and zinc chloride as a cross-linking agent. The prepared microparticles were evaluated using scanning electron microscopy (SEM) for size and particle aggregation, and Fourier Transform infrared spectroscopy (FTIR) for drug-polymer interaction, entrapment efficiency, swelling index, and in vitro drug release. Results: The % yield of chia seed mucilage was 27.35%. The pH of the mucilaginous suspension was 4.67 ± 0.50. The moisture content value was 14.56 % ± 0.50. The values of Carr's index and Hausner's ratio were 22.58 ± 1.89 and 1.38 ± 0.05, respectively. FTIR spectra showed no interaction between pure glipizide and chia seed mucilage, confirming no possible change in glipizide's pharmacology. SEM studies have confirmed the shape of the microparticles to be spherical, with average sizes ranging from 1235.18 ± 8.7 to 1423.25 ± 9.5 µm, and the drug entrapment efficiency ranged from 64.25 ± 2.52 to 81.82 ± 7.56%. The release of glipizide from the microparticles was sustained, and the Higuchi and Korsmeyer-Peppas models were found to be the best-fit kinetic models. Conclusion: The promising copolymer blend of chia seed mucilage and sodium alginate was used for the development of sustained-release dosage forms. A copolymer blend with a ratio of 1:1 produced glipizide-loaded microparticles with sustained release profiles and good mucoadhesive ability, along with a high percentage of drug entrapment efficiency.

Modified Release Interpenetrating Polymeric Network Hydrogel Beads of Montelukast Sodium Via Box Behnken Design

Background: Interpenetrating Polymeric Networks (IPN) are cross-linked polymeric alloys developed when two or more cross-linked polymers inter-penetratingly entangle. Interpenetrating polymeric networks possess several benefits including stability, biocompatibility, biodegradability, high swelling ability, and modified release efficiency. Aim: The aim of this study is to design stable, control-released montelukast sodium-loaded IPN hydrogel beads as a promising approach toward drug delivery. Objective: The goal of the present work was to develop Chitosan (swellable polymer) and glutaraldehyde (cross-linker) based modified (controlled) released montelukast sodium IPN hydrogel beads. Methods: The montelukast sodium IPN hydrogel beads were prepared via the precipitation method, and the final batch of IPN hydrogel beads was based on particle size, percent entrapment efficiency, area of swelling, and cumulative percent drug release using an overlay plot in Box-Behnken design. Compatibility studies (DSC, FT-IR) and microscopical observation (SEM) confirmed the compatibility and sphericity of the formulations. Results: The optimized (comprising 2.01% chitosan and 0.48% glutaraldehyde) IPN hydrogel beads having satisfactory particle size (817.76±54.49 μm), good entrapment efficiency (71.36±3.04%), and area of swelling (27.00±1.68 mm2) showed swelling and pH-dependent controlled montelukast release (92.96±1.05%) after 12 h with longer duration of action. Conclusion: The prepared montelukast sodium IPN hydrogel beads could be a potent control-released drug delivery vehicle.

A sustainable RP-HPLC method for concurrent estimation of capecitabine and celecoxib in liposomal formulation: Greenness and whiteness appraisal.

Liposomes have been reported for combination therapy due to their ability to carry both hydrophilic and lipophilic drugs together. The current investigation aims to develop a novel, eco-friendly, and sustainable reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous quantification of capecitabine and celecoxib co-encapsulated in liposomes. The method reported herein uses a C18 column (4.6 × 250 mm2, 5 μm) and a mobile phase consisting of water, and acetonitrile/methanol in a ratio of 60:40, containing 0.1% formic acid in both the phases. The flow rate is maintained at 1 mL/min, with an injection volume of 10 μL in the gradient mode. Detection is set at λmax = 240 nm for capecitabine and 252 nm for celecoxib. The developed liposomes are mono-disperse with a surface potential of -6.93 mV. The average size of the liposomes is 142 nm. The percentage entrapment efficiency for capecitabine is 52.39 ± 0.94%, and for celecoxib, it is 77.13 ± 0.74%. The Analytical Greenness Metric of 0.61 and Analytical Eco-Scale Score of 75 signify the greenness of the developed method. Also, the Red-Green-Blue model shows excellent whiteness, with a score of 83.2. Thus, the developed method offers a reliable, accurate, precise, buffer-free, and environment-friendly RP-HPLC approach for the simultaneous analysis of capecitabine and celecoxib co-encapsulated in liposomes.

Formulation, Development & Evaluation of Mallotus philippensis Extract Loaded NLCS based Nanogel for Psoriasi.

The current study’s objective was to develop and evaluate the potential of Bergenin-loaded nanostructured lipid carriers (NLCs) as a novel topical therapeutic for psoriasis, obtained from Mallotus philippensis. NLCs loaded with Bergenin were created using a modified Hot-melt emulsification technique, and then Box-Behnken design optimization was performed. The Independent factors were concentration of solid lipid, the concentration of liquid lipid and the concentration of surfactant. Particle size, entrapment efficiency, and drug permeation percentage were the dependent variables. The Bergenin-nano-lipid carriers (NLCs) that has been optimized has a Particle size of 148 ± 0.37 nm, an %Entrapment efficiency of 93.44 ± 0.45%, and a drug permeation percentage was found to be 83.56 ± 0.137. and the zeta potential was - 0.0617 ± 5.53 mV and the polydispersity index (PDI) was 0.30 ± 0.03. Bergenin’s existence within the NLCs was verified by FTIR. The outcomes show that Nanostructured lipid carriers have the ability to deliver Bergenin for topical psoriasis treatment.

Formulation and Evaluation of Acyclovir Loaded Transferosomal Gel for Transdermal Drug Delivery

Background: A carrying structure for targeted transdermal drug delivery is a transferosome. These unique liposomes are made of an edge activator and phosphatidylcholine. The most common antiviral drug is acyclovir, a synthetic nucleotide nucleoside analog derived from guanine. It works well to cure the varicella-zoster virus and the virus that causes herpes simplex (HSV), primarily HSV-1 and HSV-2. But its skin permeability is minimal. Therefore, this work aimed to use transferosomes to prepare acyclovir so that it could pass through the skin's barrier function. Objective: This study uses a 32-factorial factorial design to develop a transferosomal gel containing acyclovir through thin-film hydration method for painless acyclovir delivery services for skin disease treatment. Material and Methods: The independent variables are the amount of phospholipid (X1) and tween 80 (X2), while the dependent variables are particle size (Y1) and percentage entrapment efficiency (Y2). To create an ideal formulation, the produced transferosomes were assessed for particle size, in vitro drug release amount, and entrapment efficiency (EE%). A Carbopol 934 gel basis was prepared using the optimized acyclovir transferosome formulation, and its drug concentration, pH, spreadability, viscosity, and stability were assessed. Results: With small particles ranging from 176.6 to 324.4 nm, the produced acyclovir transferosomes had a high EE% range from 66.34 to 76.42 %. According to the in vitro release study, there is a negative correlation between in vitro release and EE%. The formulation TF5, including 1%w/w of carbopol 940, provides a superior profile of drug absorption in vitro. Consequently, acyclovir can enter the skin as transferosomes and cross the stratum corneum barrier. Conclusion: Acyclovir can be transformed into a transfersomal gel, which will improve antiviral efficacy, get over the skin's protective layer, prevent adverse oral reactions, and eventually improve patient adherence. Keywords: Transferosome, Transdermal drug delivery system, Acyclovir, 32 Fractional factorial design, Carbopol 934

A central composite design-based targeted quercetin nanoliposomal formulation: Optimization and cytotoxic studies on MCF-7 breast cancer cell lines

This study aimed to enhance the efficacy of quercetin (QT) by formulating it into a liposomal drug delivery system utilizing the concept of central composite design. The drug:lipid ratio, cholesterol concentration, and sonication time were selected as independent variables in the study. The vesicle and percentage entrapment efficiency were selected as the dependent variables. Quercetin nanoliposomes (QT-NLs) were prepared via a combination of ethanol injection and thin film hydration. The vesicle size and entrapment efficiency of all formulations were within the ranges of 100 nm and >80 %, respectively. The zeta potential value indicated the stability of the optimized formulation. The contour plots were used to select the desired batch range. SEM studies revealed an imperfect crystalline morphology without any unwanted agglomeration. MTT assays on VERO cell lines indicated the safety of the developed formulation. MTT assays of MCF-7 cells revealed IC50 values of 5.8 μM and 7.9 μM for QT-NLs and QT, respectively. In our study, the optimized formulation exhibited late and early apoptosis and necrosis when used to treat MCF-7 cells. S and G2/M cell cycle phases of MCF-7 cell arrest were confirmed by the cell cycle report. At sub-G0/G1 phase, 2.10 ± 1.1 %; G0/G1 phase, 34.13 ± 1.9 %; S phase, 34.55 ± 0.98 %; and G2/M phase, 26.24 ± 1.7 % of cell arrest were observed. The results demonstrated the effectiveness of the proposed design for the development of corn starch-coated QT-NLs and their activity in breast cancer cell lines.

Design and optimization of DPC-crosslinked HPβCD nanosponges for entrectinib oral delivery: formulation, characterization, and pharmacokinetic studies

BackgroundIn advanced or metastatic cancers characterized by specific genetic alterations, heightened growth and resistance to conventional therapies are common. Targeted treatments like entrectinib (ENT) precisely inhibit aberrant signaling pathways, potentially enhancing outcomes. The objective of this research is to develop and enhance the effectiveness of entrectinib-loaded nanosponge formulations by utilizing hydroxypropyl-β-cyclodextrin (HPβCD) to improve its oral bioavailability.ResultsThe study employed surface response methodology and Design-Expert® software to optimize key formulation variables such as the molar concentration ratio of the polymer and cross-linker, as well as process variables such as stirring speed and duration. Optimization focused on particle size, polydispersity index, and percentage entrapment efficiency. Validation methods encompassed Fourier transform spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), in vitro release studies, and in vivo studies.After optimization, ENT-loaded HPβCD NSPs were formulated with a molar ratio (P:CL) of 0.800 mg, stirred at 3000 rpm for 420 min, achieving a desirability of 0.926. Predicted values for PS (particle size), PdI (polydispersity index), and EE % (entrapment efficiency) were 146.98 nm, 0.263, and 88.29%, respectively. The optimized formulation showed a mean size of 151.8 ± 5.6 nm, PDI of 0.233 ± 0.049, and EE of 87.36 ± 1.61%. Further validation through various analyses confirmed the optimization's efficacy, with notable improvements demonstrated in AUC0-t (6.30-fold) and Cmax (4.10 times) compared to the free drug.ConclusionThe findings of the study indicated that nanosponges exhibit promise as an effective carrier for delivering entrectinib, addressing for advance tumor effectively by enhancing release and bioavailability in the treatment of cancer.

Intravenous delivery of furosemide using lipid-based versus polymer-based nanocapsules: in vitro and in vivo studies

Objectives Furosemide (FSM), a potent loop diuretic, is used to treat edema due to hypertension, congestive heart failure, and liver and renal failures. FSM applications are limited by its low bioavailability. Our aim is to use different nanoencapsulation strategies to control the release of FSM and enhance its pharmacokinetic properties. Methods Two types of FSM-loaded nanocapsules, namely FSM-loaded lipid nanocapsules (LNCs) and polymeric nanocapsules (PNCs), were developed, physicochemically characterized, and subjected to pharmacokinetic and pharmacodynamic studies. Lipid nanocapsules were prepared by the simple phase inversion method using LabrafacTM lipid, while the polymeric nanocapsules were prepared by nanoprecipitation method using polycaprolactone polymer. Results Transmission electron microscopy ascertains spherical structures, corroborating the nanometric diameter of both types of nanocapsules. The particle size of the optimized FSM-loaded LNCs and FSM-loaded PNCs was 32.19 ± 0.72 nm and 230.7 ± 5.13 nm, respectively. The percent entrapment efficiency was 63.56 ± 1.40% of FSM for the optimized PNCs. The in vitro release study indicated prolonged drug release compared to drug solutions. The two loaded nanocapsules systems succeeded in enhancing the pharmacokinetic parameters in comparison to the marketed FSM solution with superior diuretic activity (p < 0.05). The results of the stability study and the terminal sterilization by autoclave indicated the superiority of LNCs over PNCs in maintaining the physical parameters under storage conditions and the drastic conditions of sterilization. Conclusions LNCs and PNCs are considered promising nanosysems for improving the diuretic effect of FSM.

Extracellular vesicle-based formulation of doxorubicin: drug loading optimization, characterization, and cytotoxicity evaluation in tumor spheroids

Doxorubicin (DOX) is a chemotherapeutic with considerable efficacy, but its application is limited due to cardiotoxicity. Nanoparticles can improve DOX efficacy and prevent its adverse effects. Herein, DOX-loaded extracellular vesicles (DOX-EVs) were prepared using different loading methods including incubation, electroporation, and sonication in different hydration buffers to permeabilize nanostructures or desalinize DOX for improved entrapment. Different protein:drug (µg:µg) ratios of 1:10, 1:5, and 1:2, and incubation parameters were also investigated. The optimal formulation was characterized by western blotting, electron microscopy, Zetasizer, infrared spectroscopy, and release study. The cellular uptake and efficacy were investigated in MCF-7 spheroids via MTS assay, spheroid formation assay (SFA), confocal microscopy, and flow cytometry. The percentage of entrapment efficiency (EE) of formulations was improved from 1.0 ± 0.1 to 22.0 ± 1.4 using a protein:drug ratio of 1:2 and sonication in Tween 80 (0.1%w/v) containing buffer. Characterization studies verified the vesicles’ identity, spherical morphology, and controlled drug release properties. Cellular studies revealed the accumulation and cytotoxicity of DOX-EVs in the spheroids, and SFA and confocal microscopy confirmed the efficacy and cellular localization. Flow cytometry results revealed a comparable and amplified efficacy for DOX-EV formulations with different cell origins. Overall, the EV formulation of DOX can be applied as a promising alternative with potential advantages.

Transdermal application of diacerin loaded-terpene enriched invasomes: an approach to augment anti-edema and nociception inhibition activity

This study aimed to formulate diacerein loaded terpene-enriched invasomes (DCN-TINV) to fulfill a fruitful management of osteoarthritis. A 23 factorial design was adopted, including A: cholesterol concentration (%w/v), B: ethanol volume (mL) and C: phosphatidylcholine: drug ratio as the studied factors. Invasomes were constructed using the thin film hydration technique. Herein, percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI) and zeta potential (ZP) were statistically analyzed using Design-Expert® software to select the optimum formula. The selected criteria for detecting the optimum formula were restricting PS (<350 nm), dismissing PDI, magnifying ZP (as absolute value) and EE%. The selected formula was further scrutinized through multiple in-vitro studies, including Fourier-transform infrared spectroscopy, differential scanning calorimetry, pH measurement, stability study, release profile and transmission electron microscopy. Furthermore, the ex-vivo performance was evaluated through ex-vivo skin permeation and deposition. Finally, it was subjected to an array of in-vivo tests, namely Draize test, histopathology, In-vivo skin penetration, edema size, and nociception inhibition measurements. The optimum formula with desirability (0.913) demonstrated EE% (89.21% ± 2.12%), PS (319.75 ± 10.11 nm), ZP (−55 ± 3.96 mV) and a prolonged release profile. Intriguingly, revamped skin permeation (1143 ± 32.11 µg/cm2), nociception inhibition (77%) and In-vivo skin penetration (144 µm) compared to DCN suspension (285 ± 21.25 µg/cm2, 26% and 48 µm, respectively) were displayed. The optimum DCN-TINV exhibited plausible safety and stability profiles consolidated with auspicious efficacy for better management of osteoarthritis.

Fluconazole-Niosome-Laden Contact Lens: A Promising Therapeutic Approach for Prolonged Ocular Delivery and Enhanced Antifungal Activity

BackgroundTraditional routes of administration of fluconazole such as eye drops have a low therapeutic efficacy due to insufficient bioavailability.PurposeHerein, a fluconazole noisome-laden contact lens was prepared to control and prolong the drug release and improve its bioavailability.MethodsTwo methods have been used to prepare fluconazole niosomes: solvent injection method and thin film hydration method utilizing span 60 and cholesterol mixture. Subsequently, formulations were optimized using three factors and a two-level factorial design and were subjected to in-vitro characterization for the size of niosomes, zeta potential, entrapment efficiency percent, and cytotoxicity study. The optimized fluconazole niosomes were further entrapped in contact lenses by the soaking method and were evaluated according to in-vitro release profile, and antimicrobial activity.ResultsThe results revealed that the investigated fluconazole niosomes are of nano-size ranging from 228.2 to 769.2 nm with zeta-potential values between − 18.1 and − 60.2 mV. The entrapment efficiency percentage ranged from 51.3 to 75%. Fluconazole was released from fluconazole noisome-laden contact lens and showed a prolonged release up to 48–72 h with a cumulative release of 79.62%. Statistical analysis showed that fluconazole-noisome-laden contact lenses have a significant impressive fungal adhesion reduction as compared to fluconazole-laden contact lenses.ConclusionFluconazole noisome-laden contact lenses are a promising therapeutic way for effective and prolonged treatment of ocular fungal infection.

Karanjin-loaded soya lecithin-based ethosomal nanogel for the therapeutic intervention of psoriasis: formulation development, factorial design based-optimization, in vitro and in vivo assessment

This study aimed to develop and optimize karanjin-loaded ethosomal nanogel formulation and evaluate its efficacy in alleviating symptoms of psoriasis in an animal model induced by imiquimod. These karanjin-loaded ethosomal nanogel, were formulated to enhance drug penetration into the skin and its epidermal retention. Karanjin was taken to formulate ethosomes due to its potential ani-psoriatic activity. Ethosomes were formulated using the cold method using 32 full factorial designs to optimize the formulation components. 9 batches were prepared using two independent variables X 1: concentration of ethanol and X 2: concentration of phospholipid whereas vesicle size (Y 1) and percentage entrapment efficiency (Y 2) were selected as dependent variables. All the dependent variables were found to be statistically significant. The optimized ethosomal suspension (B3) exhibited a vesicle size of 334 ± 2.89 nm with an entrapment efficiency of 94.88 ± 1.24% and showed good stability. The morphology of vesicles appeared spherical with smooth surfaces through transmission electron microscopy analysis. X-ray diffraction analysis confirmed that the drug existed in an amorphous state within the ethosomal formulation. The optimized ethosome was incorporated into carbopol 934 to develop nanogel for easy application on the skin. The nanogel underwent characterization for various parameters including spreadability, viscosity, pH, extrudability, and percentage drug content. The ethosomal formulation remarkably enhanced the skin permeation of karanjin and increased epidermal retention of the drug in psoriatic skin compared to marketed preparation and pure drug. A skin retention study showed that ethosomal nanogel formulation has 48.33% epidermal retention in 6 h. In vivo, the anti-psoriatic activity of karanjin ethosomal nanogel demonstrated significant improvement in psoriasis, indicated by a gradual decrease in skin thickness and scaling as reflected in the Psoriasis Severity Index grading. Therefore, the prepared ethosomal nanogel is a potential vehicle for improved topical delivery of karanjin for better treatment of psoriasis.

Investigating the potential of novasomes in improving the trans-tympanic delivery of niflumic acid for effective treatment of acute otitis media

Acute otitis media (AOM) is an infection that occurs in the middle ear and may cause complications and affect quality of life. The study focused on the preparation of niflumic acid (NA) loaded novasomes for the efficient treatment of AOM through trans-tympanic drug delivery. NA loaded novasomes were formulated using Span 60 with oleic acid or lauric acid as a free fatty acid (FFA). Novasomes were prepared via ethanol injection technique using D-optimal design to evaluate the influence of 3 independent variables on the novasomes’ characteristics which are: entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP), and identify the best formula for additional investigations. The best formula determined was (N6) which contains 50 mg Span 60 and 50 mg oleic acid used as FFA. N6 exhibited EE% = 92.96 ± 0.37 %, PS = 389.25 ± 1.77 nm, PDI = 0.34 ± 0.00, and ZP = −40.90 ± 0.28 mV. N6 had a spherical shape with high elasticity. Also, it showed a sustained in vitro release compared to NA suspension. Additionally, in vivo investigations against AOM in rats and a histopathological study ensured the therapeutic effectiveness and safety of N6 and its superiority over NA suspension. Mostly, the findings showed the great efficacy of novasomes for trans-tympanic delivery of NA for the treatment of middle ear inflammation.

Design of Optimized Solid Lipid Nanoparticles of Montelukast Sodium and Assessment of Oral Bioavailability in Experimental Model.

The objective of the reported work was to develop Montelukast sodium (MS) solid lipid nanoparticles (MS-SLNs) to ameliorate its oral bio-absorption. Herein, the highpressure homogenization (HPH) principle was utilized for the fabrication of MS-SLNs. The study encompasses a 23 full factorial statistical design approach where mean particle size (Y1) and percent entrapment efficiency (Y2) were screened as dependent variables while, the concentration of lipid (X1), surfactant (X2), and co-surfactant (X3) were screened as independent variables. The investigation of MS-SLNs by DSC and XRD studies unveiled the molecular dispersion of MS into the SLNs while TEM study showed the smooth surface of developed MSSLNs. The optimized MS-SLNs exhibited mean particle size (MPS) = 115.5 ± 1.27 nm, polydispersity index (PDI) = 0.256 ± 0.04, zeta potential (ζ) = -21.9 ± 0.32 mV and entrapment efficiency (EE) = 90.97 ± 1.12 %. The In vivo pharmacokinetic study performed in Albino Wistar rats revealed 2.87-fold increments in oral bioavailability. The accelerated stability studies of optimized formulation showed good physical and chemical stability. The shelf life estimated for the developed MS-SLN was found to be 22.38 months. At the outset, the developed MS-SLNs formulation showed a significant increment in oral bioavailability and also exhibited excellent stability in exaggerated storage conditions.

D-α-tocopheryl polyethylene glycol succinate-decorated dual drug-loaded lipidic nanocarriers: A strategic approach for targeting lymphatic uptake and p-gp efflux modulation to enhance oral bioavailability in HIV-1 viral reservoirs

The toxicity potential and inadequate bioavailability of antiretroviral therapy restrict their effectiveness in completely eradicating HIV-1 from viral reservoirs, as the drugs encounter difficulties in accessing these reservoirs. This study presents a combinatorial d-α-tocopheryl polyethylene glycol succinate (TPGS)-decorated nano-structured lipid carrier of Etravirine (ETR) and Darunavir Ethanolate (DRVE) that was formulated, optimized, and characterized to achieve synergistic effects against HIV-1 infection. The effectiveness of the combinatorial approach was evaluated by in silico studies, and their docking score and free binding energy showed that both drugs demonstrate synergistic effects against their respective enzymes. The cellular research of ED (ETR and DRVE) in TMZ-b1 cell lines also showed that the best ratio of ETR and DRVE (1:6.5 μg/mL) produced a combined effect. The formulation, termed ED-TPGS-NLCs, underwent optimization using central composite rotational design (CCRD) through a modified emulsification process, followed by characterization based on globule size, polydispersity index (PDI), percentage entrapment efficiency, percentage drug loading, and transmission electron microscopy (TEM) analysis. In vitro release studies demonstrated a notable improvement of drug release from the optimized lipid nanosystem, conforming to the Korsmeyer-Peppas kinetics model. Besides, the in-vitro studies, the intestinal permeation enhancement study, the intestinal depth analysis, and the pharmacokinetic assessment of the optimized formulation in Wistar rats were performed to improve permeation and increase plasma drug concentration. ED-TPGS-NLCs also stopped HIV-1 infection in TMZ-b1 cell lines by 50 %, and the lowest concentration needed to do this was about 58 times lower than purified ED suspension. These studies ensure that ED-TPGS-NLCs were taken up due to the formation of chylomicrons and inhibit the p-gp efflux system by TPGS and solutol to inhibit the first-pass hepatic metabolism, which helps to improve the intestinal permeation and enhance plasma drug concentration, leading to enhanced oral bioavailability of ED. Hence, the improved bioavailability of ED in the nanoformulation also enhanced the anti-retroviral efficacy and improved the safety margins of ED-TPGS-NLCs. These findings can also reduce the side effects of high doses of antiretroviral drugs.

Fabrication of prostructured spanlastics gel for improving transdermal effect of dapagliflozin: In vitro characterization studies and in vivo antidiabetic activity

Dapagliflozin is a recently approved glucose-lowering agent for the management of type II diabetes mellitus. Low solubility and stability lead to its poor oral bioavailability. Prostructured spanlastic gel is very less hydrated preform of spanlastic vesicles. Therefore, the aim of this study was to explore the potential of prostructured spanlastic gel for enhancing both drug stability and transdermal delivery. The prostructured spanlastic gel formulations were fabricated by coacervation phase separation method, using Span 60 together with Tween 80 or Myrj 52 as an edge activator. Formulations were characterized for drug content, in vitro release and ex vivo skin permeability. Verification of vesicular form was assessed by hydration and the resultant formulations were characterized. Selected formulations were assessed for morphology, interaction of drug with other components, stability and antidiabetic activity. Drug content percentage of spanlastic gels was found to be in range 98.1 ± 1.9 to 94.2 ± 2.0 %. Significant (p < 0.05) increase in drug release rate was observed when edge activator concentration was greater than 30 %. Tween 80 containing formulations exhibited higher skin permeation than Myrj 52 containing ones at the same concentration of edge activator. Spanlastic vesicles were formed by hydration and had entrapment efficiency percentages ranging from 65.06 ± 0.87 % to 40.36 ± 0.95 %, mean vesicle sizes ranging from 136.1 nm to 56.52 nm and zeta potential values ranging from −29.7 mV to −6.94 mV. The morphologic examination verified formation of nanovesicular form. Thermal analysis and FT-IR confirmed encapsulation of drug inside spanlastic vesicles. Spanlastic gels showed higher stability and skin permeability when compared to vesicular form in hydroalcoholic gel. Spanlastic gels also showed prolonged hypoglycemic effect and blood glucose level reached below 135 ± 4.7 mg/dL after 24h, when compared to hydroalcoholic gel (273 ± 3 mg/dL) and oral suspension (271 ± 5 mg/dL). In conclusion, spanlastic gel could be a promising carrier for enhancing transdermal delivery of dapagliflozin, offering both sustained and enhanced antidiabetic activity.

Preparation and characterization of azelnidipine-loaded D-α-tocopheryl polyethylene glycol succinate (TPGS) / solutol micelles

Azelnidipine is a calcium-channel antagonist classified as a “class 2” drug with high permeability and low aqueous solubility. It is used in the treatment of angina pectoris and hypertension without reflex tachycardia. Improvement of the solubility of azelnidipine and increasing drug’s bioavailability can be achieved through the drug encapsulation in solutol / D-α-tocopheryl polyethylene glycol succinate (TPGS) micelles. Six formulas were prepared by direct disso¬lution after using different amounts of solutol and TPGS. TPGS and solutol act as solubilizers, permeation enhancers, and P-glycoprotein inhibitors. The particle size, particle size distribution, zeta potential, and entrapment efficiency were determined. Depending on particle size and entrapment efficiency, formula #6 was selected and subjected to in vitro dilution stability and in vitro release studies. The results obtained showed that formula #6 was the best formula, with a high entrapment efficiency percentage equal to 86.5%±0.58% and a small particle size equal to 21.9±7.75 nm that did not change significantly after dilution up to 100-fold; a fact that reveals the high thermodynamic and kinetic stability of the optimum formula. The formula #6 release profile showed a controlled release of the drug from micelles when compared to plain drug release. Based on these results, polymeric nanomicelles are regarded as a promising delivery system for azelnidipine.

Epigallocatechin-3-gallate loaded proliposomal vesicles for management of traumatic brain injury: In-vitro and in-vivo evaluation

One of the primary causes of disability and mortality worldwide is traumatic brain injury (TBI). Oxidative stress is one of the main pathological cascades of TBI. Therefore, finding an effective antioxidant for TBI is a challenge. Several studies revealed that Epigallocatechin-3-gallate (EGCG) had neuroprotective properties, so it might play an important role in TBI. However, it has some drawbacks including instability that may lead to reduced efficacy which could be enhanced using nanoformulation. Consequently, this study aimed to design and optimize EGCG-loaded Proliposomes (EGCG-PLs) and to investigate the antioxidant effect against TBI in rats by modulating the Sirt1/Nrf2/HO-1 signaling pathway. EGCG-PLs were formulated by the slurry technique. Then, to choose the best formula, nanovesicles were assessed and optimized by the Box-Behnken Design to determine the effect of preparation factors on the formed vesicles. Following that, we used an animal model of TBI to compare the neuroprotective effects of the optimized formula to the free drug in vivo. To confirm the neuroprotective action, oxidative stress biomarkers were evaluated as well as histopathological examinations of different brain tissues were performed. The optimized EGCG-loaded PLs formula had a mean size of 150.63 ± 2.65 nm while the percentage of entrapment efficiency was 89.744 ± 0.89 %. The EGCG in vitro release from the optimized PLs formula was prolonged in comparison with the free EGCG. The optimized formula showed a superior antioxidant effect compared to its free counterpart as it significantly decreased MDA and increased the endogenous antioxidants, SOD, and GSH, of brain tissues in addition to activation of the Sirt1/Nrf2/HO-1 signaling pathway. Furthermore, amelioration of histopathological alterations induced by TBI in brain tissues was more prominent with EGCG-PLs treatment. To conclude, all outcomes point to a potential enhancement in the efficacy of EGCG when prepared in PLs in combating TBI.

Characterization and Stability Test of Hydrolyzed Collagen Glyserosomes

Background: Hydrolyzed collagen is a protein obtained from enzymatic denaturation of collagen with a molecular weight of about 10 kDa, and it has been reported to produce anti-aging properties. Delivering hydrolyzed collagen into the dermis becomes a great challenge due to its large molecular weight, so glycerosome, a deformable vesicle containing glycerol as the edge activator, was developed to carry it into the dermis layer. Objective: The study aimed to determine the effect of increasing the concentration of glycerol and hydrolyzed collagen on the characteristics and stability of hydrolyzed collagen glycerosomes. Methods: Glycerosomes were composed of soy lecithin and prepared using a thin film lipid method. The lipid film was hydrated with phosphate-buffered saline pH 5 containing different glycerol concentrations (20% and 40%) and hydrolyzed collagen (2.5% and 5%). Then, characteristic tests and stability tests were carried out. Results: Hydrolyzed collagen glycerosomes had vesicle sizes of 170-180 nm, polydispersity index of 0.253-0.279, zeta potential values of -23.70 to -26.50 mV with deformability indexes of 2.25-3.49. The highest percentage of entrapment efficiency was 85.72%, achieved with a glycerol concentration of 40%. During the stability test at 25°C for 12 weeks, the hydrolyzed collagen glycerosomes did not experience pH and entrapment efficiency changes, but it increased the vesicle size. Conclusion: The use of 40% glycerol produced more deformable vesicles than 20% glycerol in hydrolyzed collagen glycerosomes; however, a formula improvement is required to improve the stability of glycerosomes.