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The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Various chitosan (CS)-based nanoparticles (CS-NPs) of ciprofloxacin hydrochloride (CHCl) have been investigated for therapeutic delivery and to enhance antimicrobial efficacy. However, the Box-Behnken design (BBD)-supported statistical optimization of NPs of CHCl has not been performed in the literature. As a result, the goal of this study was to look into the key interactions and quadratic impacts of formulation variables on the performance of CHCl-CS-NPs in a systematic way. To optimize CHCl-loaded CS-NPs generated by the ionic gelation process, the response surface methodology (RSM) was used. The BBD was used with three factors on three levels and three replicas at the central point. Tripolyphosphate, CS concentrations, and ultrasonication energy were chosen as independent variables after preliminary screening. Particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), and in vitro release were the dependent factors (responses). Prepared NPs were found in the PS range of 198-304 nm with a ZP of 27-42 mV. EE and drug release were in the range of 23-45% and 36-61%, respectively. All of the responses were optimized at the same time using a desirability function based on Design Expert ® modeling and a desirability factor of 95%. The minimum inhibitory concentration (MIC) of the improved formula against two bacterial strains, Pseudomonas aeruginosa and Staphylococcus aureus , was determined. The MIC of the optimized NPs was found to be decreased 4-fold compared with pure CHCl. The predicted and observed values for the optimized formulation were nearly identical. The BBD aided in a better understanding of the intrinsic relationship between formulation variables and responses, as well as the optimization of CHCl-loaded CS-NPs in a time- and labor-efficient manner.

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.

Breast cancer is the most common cancer in females and ranked second after skin cancer. The use of natural compounds is a good alternative for the treatment of breast cancer with less toxicity than synthetic drugs. The aim of the present study is to develop and characterize hybrid Apigenin (AN) Nanoparticles (NPs) for oral delivery (AN-NPs). The hybrid AN-NPs were prepared by the self-assembly method using lecithin, chitosan and TPGS. Further, the NPs were optimized by Box-Behnken design (3-factor, 3-level). The hybrid NPs were evaluated for particle size (PS), entrapment efficiency (EE), zeta potential (ZP), and drug release. The optimized hybrid NPs (ON2), were further evaluated for solid state characterization, permeation, antioxidant, cytotoxicity and antimicrobial study. The formulation (ON2) exhibited small PS of 192.6 ± 4.2 nm, high EE 69.35 ± 1.1%, zeta potential of +36.54 mV, and sustained drug release (61.5 ± 2.5% in 24 h), as well as significantly ( p < 0.05) enhanced drug permeation and antioxidant activity. The IC 50 of pure AN was found to be significantly ( p < 0.05) lower than the formulation (ON2). It also showed significantly greater ( p < 0.05) antibacterial activity than pure AN against Bacillus subtilis and Salmonella typhimurium . From these findings, it revealed that a hybrid AN polymeric nanoparticle is a good carrier for the treatment of breast cancer.

Cancer is the leading cause of human disease and death worldwide, accounting for 7.6 million deaths per year and projected to reach 13.1 million by 2030. Many phytochemicals included in traditional medicine have been utilized in the management of cancer. Conventional chemotherapy is generally known to be the most effective treatment of metastatic cancer but these cancerous cells might grow resistant to numerous anticancer drugs over time that resulting in treatment failure. This review tried to portray the advancement in the anticancer and chemopreventive effects of several phytochemicals and some of its members encapsulated in the nano-based delivery system of the drug. It comprises the issue associated with limited use of each phytoconstituents in human cancer treatment are discussed, and the benefits of entrapment into nanocarriers are evaluated in terms of drug loading efficiency, nanocarrier size, release profile of the drug, and in vitro and/or in vivo research and treatment testing, such as cytotoxicity assays and cell inhibition/viability., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cancer is a group of disorders characterized by uncontrolled cell growth that affects around 11 million people each year globally. Nanocarrier-based systems are extensively used in cancer imaging, diagnostics as well as therapeutics; owing to their promising features and potential to augment therapeutic efficacy. The focal point of research remains to develop new-fangled smart nanocarriers that can selectively respond to cancer-specific conditions and deliver medications to target cells efficiently. Nanocarriers deliver loaded therapeutic cargos to the tumour site either in a passive or active mode, with the least drug elimination from the drug delivery systems. This review chiefly focuses on current advances allied to smart nanocarriers such as dendrimers, liposomes, mesoporous silica nanoparticles, quantum dots, micelles, superparamagnetic iron-oxide nanoparticles, gold nanoparticles and carbon nanotubes, to list a few. Exhaustive discussion on crucial topics like drug targeting, surface decorated smart-nanocarriers and stimuli-responsive cancer nanotherapeutics responding to temperature, enzyme, pH and redox stimuli have been covered.

Luteolin (LUT) is a natural pharmaceutical compound that is weakly water soluble and has low bioavailability when taken orally. As a result, the goal of this research was to create self-nanoemulsifying drug delivery systems (SNEDDS) for LUT in an attempt to improve its in vitro dissolution and hepatoprotective effects, resulting in increased oral bioavailability. Using the aqueous phase titration approach and the creation of pseudo-ternary phase diagrams with Capryol-PGMC (oil phase), Tween-80 (surfactant), and Transcutol-HP (co-emulsifier), various SNEDDS of LUT were generated. SNEDDS were assessed for droplet size, polydispersity index (PDI), zeta potential (ZP), refractive index (RI), and percent of transmittance (percent T) after undergoing several thermodynamic stability and self-nanoemulsification experiments. When compared to LUT suspension, the developed SNEDDS revealed considerable LUT release from all SNEDDS. Droplet size was 40 nm, PDI was <0.3, ZP was -30.58 mV, RI was 1.40, percent T was >98 percent, and drug release profile was >96 percent in optimized SNEDDS of LUT. For in vivo hepatoprotective testing in rats, optimized SNEDDS was chosen. When compared to LUT suspension, hepatoprotective tests showed that optimized LUT SNEDDS had a substantial hepatoprotective impact. The findings of this investigation suggested that SNEDDS could improve bioflavonoid LUT dissolution rate and therapeutic efficacy.

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

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

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

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

The present research work was designed to develop dorzolamide-loaded chitosan-coated polycaprolactone nanoparticles (DRZ-CS-PCL-NPs) for improved ocular delivery. The nanoparticles were prepared by single-step emulsification technique and optimized using the three-factor three-level Box-Behnken design. The optimized DRZ-CS-PCL-NPs prepared with the composition of polycaprolactone (60 mg), chitosan (0.6%) and polyvinyl alcohol (1.5%). The particle size, polydispersity index, zeta potential and encapsulation efficiency of optimized DRZ-CS-PCL-NPs were found to be 192.38 ± 6.42 nm, 0.18 ± 0.04, +5.21 ± 1.24 mV, and 72.48 ± 5.62%, respectively. The dependent and independent response variables showed excellent correlation and signifying the rationality of the optimized DRZ-CS-PCL-NPs. The DRZ release from CS-PCL-NPs showed biphasic behaviour with initial burst release for 2 h after that sustained-release up to 12 h of study. The corneal flux experiment showed many fold enhancement in permeation across goat cornea. DRZ-CS-PCL-NPs exhibited 3.7 fold higher mucoadhesive strength compared to the control. Furthermore, the histopathological assessment and HET-CAM study revealed that the DRZ-CS-PCL-NPs were non-irritant and safe for ocular administration. Therefore, from the present study, it can be concluded that the optimized DRZ-CS-PCL-NPs are safe and have the potential for successful ocular delivery and improved therapeutic efficacy., Competing Interests: Declaration of competing interest All authors have approved the final manuscript, and the authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The topically administered drugs through conventional delivery systems have low bioavailability. Henceforth, the present study was designed to prepare and optimize clarithromycin (CTM)-loaded chitosan nanoparticles (CHNPs) to demonstrate the efficacy against microorganisms., Methods: Clarithromycin-loaded chitosan nanoparticles (CTM-CHNPs) were prepared by ionotropic gelation method. The formulation was optimized by box-Behnken design using the formulation variables like CH (A), STPP concentration (B), and stirring speed (C). Their effects were evaluated on the independent variables like particle size (Y 1 ) and entrapment efficiency (Y 2 ). Further, CTM-CHNPs were evaluated for physicochemical parameters, in-vitro drug release, ex-vivo permeation, bioadhesive study, corneal hydration, histopathology, HET-CAM, and antibacterial study., Results: The optimized formulation (CTM-CHNPopt) showed the low particle size (152±5 nm), which is desirable for ocular delivery. It also showed high encapsulation (70.05%), zeta potential (+35.2 mV), and was found in a spherical shape. The drug release study revealed a sustained drug release profile (82.98±3.5% in 12 hours) with Korsmeyer peppas kinetic (R 2 =0.996) release model. It showed a 2.7-fold higher corneal permeation than CTM-solution. CHNPs did not exhibit any sign of damage to excised goat cornea, which is confirmed by hydration, histopathology, and HET-CAM test. It exhibited significant ( P <0.05) higher antibacterial susceptibility than CTM-solution., Conclusion: The finding of the study concluded that CTM-CHNPs can be used for effective management of bacterial conjunctivitis by increasing the precorneal residence time., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Bin-Jumah et al.)

This research work aimed to prepare and optimize "self-nanoemulsifying drug delivery system (SNEDDS)" by applying full factorial design (FFD) to improve solubilization and subsequently antiinflammatory efficacy of flufenamic acid (FLF). Suitable excipients were screened out based on the maximum solubility of FLF. FFD was applied using lipid (X 1 ) and surfactant (X 2 ) as independent variables against droplet size (Y 1 , nm), zeta potential (Y 2 , mV) and polydispersity index (PDI, Y 3 ). Desirability function identified the main factors influencing the responses and possible interactions. Moreover, the optimized formulation (OFS1) was characterized and compared with pure FLF suspension. The prepared formulations (FS1-FS9) showed the size, PDI and zeta potential of 14.2-110.7 nm, 0.29-0.62 and -15.1 to -28.6 mV, respectively. The dispersion and emulsification of all formulations meted out within 2 min suggesting immediate release and successful solubilization. The optimized formulation OFS1 demonstrated ~ 85% drug release within 1 h which was significantly higher (p ˂ 0.05) than FLF suspension. The hemolysis study negated the probable interaction with blood cells. Eventually, improved anti-inflammatory efficacy was envisaged which might be attributed to increased drug solubility and absorption. The present nanocarrier could be a promising approach and alternative to conventional dosage form.

Purpose: The present study was designed to study the gentamycin (GTM)-loaded stimulus-responsive chitosan nanoparticles to treat bacterial conjunctivitis., Methods: GTM-loaded chitosan nanoparticles (GTM-CHNPs) were prepared by ionotropic gelation method and further optimized by 3-factor and 3-level Box-Behnken design. Chitosan (A), sodium tripolyphosphate (B), and stirring speed (C) were selected as independent variables. Their effects were observed on particle size (PS as Y1), entrapment efficiency (EE as Y2), and loading capacity (LC as Y3)., Results: The optimized formulation showed the particle size, entrapment efficiency, and loading capacity of 135.2±3.24 nm, 60.18±1.65%, and 34.19±1.17%, respectively. The optimized gentamycin-loaded chitosan nanoparticle (GTM-CHNPopt) was further converted to the stimulus-responsive sol-gel system (using pH-sensitive carbopol 974P). GTM-CHNPopt sol-gel (NSG5) exhibited good gelling strength and sustained release (58.99±1.28% in 12h). The corneal hydration and histopathology of excised goat cornea revealed safe to the cornea. It also exhibited significant (p<0.05) higher ZOI than the marketed eye drop., Conclusion: The finding suggests that GTM-CHNP-based sol-gel is suitable for ocular delivery to enhance the corneal contact time and improved patient compliance., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Alruwaili et al.)

Purpose: This study evaluated the stereoisomeric effect of L- and D-penetratin-cell-penetrating peptides (CPPs)-incorporated insulin-loaded solid lipid nanoparticles (INS-SLNs) on the bioavailability (BA) of oral insulin (INS)., Methods: Insulin-loaded solid nanoparticles, L-penetratin-INS-SLNs (LP-INS-SLNs), and D-penetratin-INS-SLNs (DP-INS-SLNs) were formulated by double emulsification. The developed SLNs were evaluated for particle size, zeta potential (ZP), and drug encapsulation and subjected to differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and evaluated for stability against enzymatic degradation in rat intestinal fluid. Finally, the SLNs were administered to rats to evaluate the BA of INS-SLNs that contained L- and D-penetratin., Results: The mean particle size, PDI, and ZP values of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 618.5 to 973.0 nm, 0.227 to 0.734, and -17.0 to -23.7 mV, respectively. The encapsulation efficiency (%EE) and drug loading (%DL) of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 59.03% to 67.42% and from 1.62% to 1.82%, respectively. Differential scanning calorimetry and FTIR analyses indicated that INS was successfully encapsulated in SLNs. Enzymatic degradation of DP-INS-SLNs was slower in intestinal fluid, and the half-life (t 1/2 ) was significantly prolonged, compared to all other SLNs. The pharmacological availability (PA) and BA of orally administered LP-INS-SLNs, which were the most effective SLNs, were 13.1% and 15.7% relative to s.c. administration, respectively., Conclusion: Penetratin stereochemistry significantly impacted oral BA of INS-SLNs, which are promising carriers for oral INS administration., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Alsulays et al.)

Domperidone (DOP) is extensively applied orally in the management of nausea and vomiting. Upon oral administration, its bioavailability is very poor due to its poor solubility in alkaline media. Therefore, the aim of this work was to investigate DOP-loaded solid lipid nanoparticles (DOP-SLNs) in order to sustain its release pattern and to enhance oral bioavailability. DOP-SLNs were prepared using four different lipids. Prepared DOP-SLNs were characterized for "polydispersity index (PDI), particle size, zeta potential, % entrapment efficiency (% EE), and drug release behavior." Differential scanning calorimetry (DSC) study was carried out to illustrate the physical form of DOP and excipients. The morphology of DOP-SLNs was confirmed by scanning electron microscopy (SEM). Pharmacokinetic study on optimized DOP-SLN in comparison to tablet was performed in rats. The "particle size, PDI, zeta potential, and % EE" of optimized formulation (F5) were recorded as 201.4 nm, 0.071, - 6.2 mV, and 66.3%, respectively. DSC thermograms suggested amorphous state of DOP in various SLNs. Surface morphology of SLNs using SEM suggested spherical shape of the nanoparticles within nanometer size range. In vitro release studies confirmed that all SLN formulations possessed a sustained release over a period of 12 h (51.3% from optimized formulation) in comparison with immediate release from conventional tablets (100% after 90 min). Pharmacokinetic study showed significant enhancement in oral absorption of DOP from optimized SLN in comparison with DOP tablet. The enhancement in relative bioavailability of DOP from optimized SLN was 2.62-fold in comparison with DOP tablet.

Background: Nano drug delivery systems have the potential to address the challenges of delivering BCS Class II and IV drugs like furosemide. The purpose of the current study is to prepare stable nanosuspension and investigate in vitro dissolution performance of the model compound furosemide using quality by design (QbD) approach., Methods: Nanosuspension batches with uniform particle size were prepared for furosemide using the antisolvent precipitation method. A quality by design (Qbd) approach was explored to understand the impact of process parameters (stirring time, stirring speed, temperature, and injection rate) and material attributes (drug concentration, stabilizer type, drug: stabilizer ratio, and antisolvent: solvent ratio) on the quality attributes of furosemide nanosuspension using a full factorial experimental design. Multiple linear regression and ANOVA were employed to estimate and identify the critical process parameters and material attributes. Injection rate and stirring time were identified as the most critical process parameters' affecting the quality attributes of furosemide nanosuspension., Results: Individual material attributes did not show significant impact on the average particle size of the nanocrystals, however two-way interactions between material attributes (stabilizer type/drug concentration and stabilizer type/antisolvent: solvent ratio) significantly affected nanosuspension particle size distribution. Solid state characterization (PXRD, DSC and SEM) did not exhibit any changes of physical form during preparation and optimization of the furosemide nanosuspension. Dissolution of the furosemide nanocrystals in gastric media was significantly higher than that observed for micronized furosemide suspension and raw furosemide powder. Stability study data suggests that optimized batches of furosemide nanosuspensions were stable for three months at 4°C and ambient conditions., Conclusion: The antisolvent precipitation method can produce stable furosemide nanosuspensions with desirable quality attributes and enhancement of dissolution rate in the gastric medium as compared to the raw furosemide powder and microsuspension., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The current study aimed to prepare a topical gel containing solid lipid nanoparticles (SLNs) encapsulating fluoxetine for diabetic wound healing effects. Fluoxetine (FX) was loaded into SLNs by employing an emulsion solvent evaporation technique using stearic acid as a lipid, and soya lecithin as a surfactant. SLNs were then evaluated for particle size, polydispersity index (PDI), zeta potential (ZP), percent entrapment efficiency (%EE), percent drug loading (%DL), and in vitro drug release. The optimized SLN (FS3) composed of FX (100 mg), SA (150 mg), and SA (100 mg) displayed mean particle size (467.3 ± 2.2nm), PDI (0.435 ± 0.02), ZP (−32.2 ± 4.47mV), EE (95.8 ± 3.38%), and DL (16.4 ± 2.4%). FTIR and DSC studies denote drug-polymer compatibility and the amorphous nature of FX in the SLNs. The drug release at 24 h was found to be (98.89 ± 2.57%) which followed the fickian diffusion mechanism. SLN (FS3) was further loaded into carbopol gel and tested for pH, spreadability, and extrudability of pharmaceutical parameters. In-vitro release of FX from the SLN gel and plain gel was compared, diabetic wound healing gel (DWH) showed sustained drug delivery. An in vivo study was also performed for DWH gel in streptozotocin-induced diabetic rats. Histopathological examination exhibited DWH gel-treated wounds have increased hydroxyproline, cellular proliferation, a rise in the number of blood vessels, and the level of collagen synthesis. Thus, DWH gel-loaded SLN encapsulated with FX could be a potential carrier for the effective treatment and management of diabetic wounds. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) were synthesized using citrate reduction, also known as the Turkevich method. The AuNPs were compared with the commercially available product and later subjected to characterization. The AuNPs were 13 nm in diameter with a 2.7 × 108 M−1cm−1 extension coefficient. The calculated concentration was 5.1 nM through the Beer–Lambert law using UV–vis absorbance spectra. Further detailed characterization was applied, such as scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), elemental analysis using electro and DLS instruments, energy-dispersive X-ray spectroscopy (EDS), XRD, and Zeta potential. The synthesized AuNPs had a higher UV-absorbance peak of 0.93 in comparison to commercially available nanoparticles at 5.8 identical conditions. The characterization confirmed successful fabrication of colloidal-citrate-capped AuNPs and their dispersed and aggregated state with induced salt concentration. The shape and morphology were confirmed through XRD, showing a face-centered cubic lattice of {111}, confirmed at 38.1 round shape, and a crystalline lattice. AuNPs tend to be applied in sensing, detection, drug delivery, pharmaceuticals, and other applications in the environment and materials. Other applications include environmental contaminant detection, colorimetric sensors, antimicrobial applications, biosensing and drug delivery, tissue engineering, nanomedicines, optoelectronics, and catalysts. [ABSTRACT FROM AUTHOR]

The goal of this study was to optimize and formulate apigenin (APG)-loaded pegylated chitosan nanoparticles (PEGylated-CNPs) via ionic gelation techniques using the Box–Behnken design (BBD). Three individual variables, X1(chitosan: TPP concentration), X2 (PEG-400 concentration), and X3 (sonication time), were investigated for their influence on response variables (Y1—particle size (PS); Y2—drug entrapment efficiency (DEE); and Y3—zeta potential (ZP). The optimized formula of APG-PEGylated CNPs was picked from the statistical design and was then examined for physical, morphological, release characterization, anti-oxidant, and anti-tumor potential. The average PS, PDI, %DEE, and ZP were found to be 139.63 ± 5.67 nm, 0.296 ± 0.014, 79.55 ± 3.12%, and 24.68 ± 1.84 mV, respectively. The optimized APG formulation was chosen and reformulated based on the desirability function. Results of the observed and predicted values of responses through the BBD process were found to be nearly identical. The resulting APG-PEGylated CNPs were spherical and smooth, according to surface morphology studies. The release study revealed that PEGylated-CNPs exhibited biphasic release patterns distinguished by an initial burst release of APG only at early phases accompanied by a delayed release near 24 h. Furthermore, APG-PEGylated CNPs demonstrated statistically increased antioxidant activities and cytotoxicity against MCF-7 cells compared to pure APG. Based on the findings, it is possible to conclude that BBD was efficient in optimizing the PEGylated CNPs formulation and recognizing the impacts of formulation variables. In conclusion, the developed formulation has a significant potential for anticancer therapy. [ABSTRACT FROM AUTHOR]

The clinical application of phytochemicals such as thymoquinone (THQ) is restricted due to their limited aqueous solubility and oral bioavailability. Developing mucoadhesive nanocarriers to deliver these natural compounds might provide new hope to enhance their oral bioavailability. Herein, this investigation aimed to develop THQ-loaded lipid-polymer hybrid nanoparticles (THQ-LPHNPs) based on natural polymer chitosan. THQ-LPHNPs were fabricated by the nanoprecipitation technique and optimized by the 3-factor 3-level Box–Behnken design. The optimized LPHNPs represented excellent properties for ideal THQ delivery for oral administration. The optimized THQ-LPHNPs revealed the particles size (PS), polydispersity index (PDI), entrapment efficiency (%EE), and zeta potential (ZP) of <200 nm, <0.25, >85%, and >25 mV, respectively. THQ-LPHNPs represented excellent stability in the gastrointestinal milieu and storage stability in different environmental conditions. THQ-LPHNPs represented almost similar release profiles in both gastric as well as intestinal media with the initial fast release for 4 h and after that a sustained release up to 48 h. Further, the optimized THQ-LPHNPs represent excellent mucin binding efficiency (>70%). Cytotoxicity study revealed much better anti-breast cancer activity of THQ-LPHNPs compared with free THQ against MDA-MB-231 and MCF-7 breast cancer cells. Moreover, ex vivo experiments revealed more than three times higher permeation from the intestine after THQ-LPHNPs administration compared to the conventional THQ suspension. Furthermore, the THQ-LPHNPs showed 4.74-fold enhanced bioavailability after oral administration in comparison with the conventional THQ suspension. Therefore, from the above outcomes, mucoadhesive LPHNPs might be suitable nano-scale carriers for enhanced oral bioavailability and therapeutic efficacy of highly lipophilic phytochemicals such as THQ. [ABSTRACT FROM AUTHOR]

This review tries to summarize the purpose of steadily developing surface-functionalized nanoparticles for various bio-applications and represents a fascinating and rapidly growing field of research. Due to their unique properties—such as novel optical, biodegradable, low-toxicity, biocompatibility, size, and highly catalytic features—these materials are considered superior, and it is thus vital to study these systems in a realistic and meaningful way. However, rapid aggregation, oxidation, and other problems are encountered with functionalized nanoparticles, inhibiting their subsequent utilization. Adequate surface modification of nanoparticles with organic and inorganic compounds results in improved physicochemical properties which can overcome these barriers. This review investigates and discusses the iron oxide nanoparticles, gold nanoparticles, platinum nanoparticles, silver nanoparticles, and silica-coated nanoparticles and how their unique properties after fabrication allow for their potential use in a wide range of bio-applications such as nano-based imaging, gene delivery, drug loading, and immunoassays. The different groups of nanoparticles and the advantages of surface functionalization and their applications are highlighted here. In recent years, surface-functionalized nanoparticles have become important materials for a broad range of bio-applications. [ABSTRACT FROM AUTHOR]

Apigenin (AGN) is a potent phytochemical with strong antioxidant and anticancer potential. But its therapeutic efficacy is limited due to its high lipophilic characteristics. Therefore, the present investigation aimed to develop AGN-loaded polymer-lipid hybrid nanoparticles (AGN-PLHNPs). Herein, we successfully developed AGN-PLHNPs and optimized them by a 33-Box-Behnken de-sign. The poly (lactic-co-glycolic acid) (PLGA; coded as F1), phospholipon 90 G (PL-90G; coded as F2), and poloxamer 188 (P-188; coded as F3) were considered as the independent factors while particle size (PS; coded as R1), entrapment efficiency (%EE; R2), and cumulative drug release (%CDR; R3) were selected as dependent responses. The average PS, %EE, and %CDR of the AGN-PLHNPs were observed in the range of 101.93 nm to 175.26 nm, 58.35% to 81.14%, and 71.21% to 93.31%, respectively. The optimized AGN-PLHNPs revealed better homogeneity (poly-dispersity index < 0.2) and colloidal stability with high zeta potential (>25 mV). It also exhibited fast release in the initial 4 h after that sustained release up to 48 h of study. Moreover, the results of both DPPH as well as ABTS assays revealed significant improvement in the antioxidant activity. Furthermore, the optimized AGN-PLHNPs exhibited enhanced cytotoxicity efficacy against MCF-7 as well as MDA-MB-231 breast cancer cell lines. [ABSTRACT FROM AUTHOR]

The present research work is designed to prepare and optimize butenafine (BT) loaded poly lactic co glycolic acid (PLGA) nanoparticles (BT-NPs). BT-NPs were prepared by emulsification probe sonication method using PLGA (A), PVA (B) as polymer and stabilizer, respectively. The optimum composition of BT-NPs was selected based on the point prediction method given by the Box Behnken design software. The optimized composition of BT-NPop showed a particle size of 267.21 ± 3.54 nm with an entrapment efficiency of 72.43 ± 3.11%. The optimum composition of BT-NPop was further converted into gel formulation using chitosan as a natural polymer. The prepared topical gel formulation (BTNPopG) was further evaluated for gel characterization, drug release, permeation study, irritation, and antifungal studies. The prepared BT-NPopG formulation showed optimum pH, viscosity, spreadability, and drug content. The release and permeation study results revealed slow BT release (42.76 ± 2.87%) with significantly enhanced permeation across the egg membrane. The irritation study data showed negligible irritation with a cumulative score of 0.33. The antifungal study results conclude higher activity than marketed as well as pure BT. The overall conclusion of the results revealed BT-NPopG as an ideal delivery system to treat topical fungal infection. [ABSTRACT FROM AUTHOR]

The aim of the study was to prepare lansoprazole (LNS)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles in order to improve the physicochemical stability associated with LNS. We synthesized LNS-loaded PLGA nanoparticles in the presence of magnesium oxide as alkalizer to improve the release of LNS and stability against photodegradation. The LNS-encapsulated PLGA nanoparticles were developed by the nanoprecipitation/solvent evaporation method, resulting in a particle size of 246.7 ± 3.4 nm, polydispersity index (PDI) of 0.126, percent drug entrapment (PDE) of 82.85 ± 4.5%, percent drug loading (PDL) of 3.54 ± 0.34%, and pH of 8.10 ± 0.56. The developed nanoparticles were further evaluated for in vitro release and resistance to photodegradation by NMR spectroscopy and LC-MS. The sustained release of the drug was confirmed after the encapsulation of LNS in the PLGA matrix. The protection of LNS in the PLGA matrix against photodegradation was confirmed by NMR and LC-MS studies. The LC-MS of UV-exposed samples of pure LNS and LNS-loaded PLGA nanoparticles at 254 nm showed the same (M + 1) peak at 370 m/e, and the base peak at 369 m/e accounted for the unchanged structure of LNS inside PLGA nanoparticles. Overall, it was proved that PLGA nanoparticles in the presence of magnesium oxide are an efficient carrier to deliver and protect LNS from physicochemical instability. [ABSTRACT FROM AUTHOR]

Cancer is a group of disorders characterized by uncontrolled cell growth that affects around 11 million people each year globally. Nanocarrier-based systems are extensively used in cancer imaging, diagnostics as well as therapeutics; owing to their promising features and potential to augment therapeutic efficacy. The focal point of research remains to develop new-fangled smart nanocarriers that can selectively respond to cancer-specific conditions and deliver medications to target cells efficiently. Nanocarriers deliver loaded therapeutic cargos to the tumour site either in a passive or active mode, with the least drug elimination from the drug delivery systems. This review chiefly focuses on current advances allied to smart nanocarriers such as dendrimers, liposomes, mesoporous silica nanoparticles, quantum dots, micelles, superparamagnetic iron-oxide nanoparticles, gold nanoparticles and carbon nanotubes, to list a few. Exhaustive discussion on crucial topics like drug targeting, surface decorated smart-nanocarriers and stimuli-responsive cancer nanotherapeutics responding to temperature, enzyme, pH and redox stimuli have been covered. [ABSTRACT FROM AUTHOR]

The excellent therapeutic potential of a variety of phytochemicals in different diseases has been proven by extensive studies throughout history. However, most phytochemicals are characterized by a high molecular weight, poor aqueous solubility, limited gastrointestinal permeability, extensive pre-systemic metabolism, and poor stability in the harsh gastrointestinal milieu. Therefore, loading of these phytochemicals in biodegradable and biocompatible nanoparticles (NPs) might be an effective approach to improve their bioactivity. Different nanocarrier systems have been developed in recent decades to deliver phytochemicals. Among them, NPs based on chitosan (CS) (CS-NPs), a mucoadhesive, non-toxic, and biodegradable polysaccharide, are considered the best nanoplatform for the oral delivery of phytochemicals. This review highlights the oral delivery of natural products, i.e., phytochemicals, encapsulated in NPs prepared from a natural polymer, i.e., CS, for improved bioavailability and bioactivity. The unique properties of CS for oral delivery such as its mucoadhesiveness, non-toxicity, excellent stability in the harsh environment of the GIT, good solubility in slightly acidic and alkaline conditions, and ability to enhance intestinal permeability are discussed first, and then the outcomes of various phytochemical-loaded CS-NPs after oral administration are discussed in detail. Furthermore, different challenges associated with the oral delivery of phytochemicals with CS-NPs and future directions are also discussed. [ABSTRACT FROM AUTHOR]

In the present study, thymoquinone (TQ)-encapsulated chitosan- (CS)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were formulated using the emulsion evaporation method. NPs were optimized by using 33-QbD approach for improved efficacy against breast cancer. The optimized thymoquinone loaded chitosan coated Poly (d,l-lactide-co-glycolide) nanoparticles (TQ-CS-PLGA-NPs) were successfully characterized by different in vitro and ex vivo experiments as well as evaluated for cytotoxicity in MDA-MB-231 and MCF-7 cell lines. The surface coating of PLGA-NPs was completed by CS coating and there were no significant changes in particle size and entrapment efficiency (EE) observed. The developed TQ-CS-PLGA-NPs showed particle size, polydispersibility index (PDI), and %EE in the range between 126.03–196.71 nm, 0.118–0.205, and 62.75%–92.17%. The high and prolonged TQ release rate was achieved from TQ-PLGA-NPs and TQ-CS-PLGA-NPs. The optimized TQ-CS-PLGA-NPs showed significantly higher mucoadhesion and intestinal permeation compared to uncoated TQ-PLGA-NPs and TQ suspension. Furthermore, TQ-CS-PLGA-NPs showed statistically enhanced antioxidant potential and cytotoxicity against MDA-MB-231 and MCF-7 cells compared to uncoated TQ-PLGA-NPs and pure TQ. On the basis of the above findings, it may be stated that chitosan-coated TQ-PLGA-NPs represent a great potential for breast cancer management. [ABSTRACT FROM AUTHOR]

Purpose: To develop poly-lactic-co-glycolic acid (PLGA) -based nanoparticles (NPs) for the delivery of sunitinib malate (STM) to colon cancer cells. Methods: Three different formulations (F1 - F3) were developed by nano-precipitation technique using various concentrations of PLGA. The NPs were evaluated for particle size, polydispersity index, zeta potential, drug entrapment, and drug loading, using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Furthermore, in vitro drug release and anticancer studies were carried out on the formulations. Results: Among the three NPs, optimized NP (F3) of STM was chosen for in vitro anti-cancer study against H-29 human colon cancer cells lines based on its particle size (132.9 nm), PDI (0.115), zeta potential (-38.12 mV), entrapment efficiency (52.42%), drug loading (5.24%), and drug release (91.26% in 48 h). A significant anti-cancer activity of the optimized NPs was observed, relative to free STM. Conclusion: These findings suggest that STM-loaded NPs possess significant anti-cancer activity against human colon cancer HT-29 cells lines. [ABSTRACT FROM AUTHOR]