Syrupy herbal formulation of green bean pod extract of Phaseolus vulgaris L.: Formulation optimization by central composite design, and evaluation for anti-urolithiatic activity.

The green bean pods of Phaseolus vulgaris L. are traditionally used as a folk remedy for treating calcium oxalate kidney stones. The current research aimed to develop a syrup formulation containing green bean pod extract for anti-urolithiatic activity. The syrup was prepared using a simple blending method and optimized through a central composite design (CCD) with two independent variables: the ratio of pod juice (PJ) to sugar solution (SS) ranging from 1:0.5 to 1:1.5, and the percentage of CMC from 0.2% to 0.4% w/v. These variables were analyzed for their impact on viscosity (CP) and sedimentation percentage, helping to identify the best formulation out of 13 variants. The finalized formulation (F-opt) underwent assessment for physicochemical characteristics such as organoleptic properties, viscosity, density, sedimentation rate, and stability. Additionally, a microbiological assessment was performed utilizing the spread plate method. Further, it was evaluated for in vitro, ex vivo, and in vivo anti-urolithiatic activity in rat models for 28 days and compared with that of the reference standard (Cystone syrup). Additionally, acute toxicity was assessed in albino Swiss mice. Histopathological evaluations were then conducted on the kidneys of the Wistar rats that had been used for the in vivo studies, providing insight into the treatment effects on kidney tissue structure. The optimized formulation (F-opt) was a green, viscous, clear syrup with a pH of 5.8, a viscosity of 256.38 CP, a density of 1.31 g/ml, and a sedimentation rate of 0.69%. The optimized formulation was found to be stable, showing no significant changes in physicochemical and microbiological properties. The results of the in vitro, ex vivo, and in vivo anti-urolithiatic studies indicated that the optimized formulation effectively inhibited the aggregation of calcium oxalate. The acute toxicity studies revealed no mortality or adverse effects for both the optimized formulation and pure bean pod juice at a dose of 2000 mg/kg body weight. Histopathological examination revealed that rats treated with the optimized formulation exhibited a significant reduction in both the number and size of calcium oxalate deposits within various parts of the renal tubules. It can be concluded that the syrupy formulation of Phaseolus vulgaris L. green bean pod extract demonstrated significant anti-urolithiatic activity. This activity could be due to its diuretic properties and its ability to inhibit the formation of calcium oxalate crystals. However, limitations of the study included a lack of elucidation of the mechanism and limited generalizability of the findings.

Novel Products as Promising Therapeutic Agents for Angiogenesis Inhibition.

OBJECTIVE: Angiogenesis is the process of forming new blood vessels from pre-existing vessels and occurs during development, wound healing, and tumor growth. In this review, we aimed to present a comprehensive view of various factors contributing to angiogenesis during carcinogenesis. Anti-angiogenesis agents prevent or slow down cancer growth by interrupting the nutrients and blood supply to the tumor cells, and thus can prove beneficial for treatment. METHOD: The discovery of several novel angiogenic inhibitors has helped to reduce both morbidity and mortality from several life-threatening diseases, such as carcinomas. There is an urgent need for a new comprehensive treatment strategy combining novel anti-angiogenic agents for the control of cancer. The article contains details of various angiogenic inhibitors that have been adopted by scientists to formulate and optimize such systems in order to make them suitable for cancer. RESULTS: The results of several researches have been summarized in the article and all of the data support the claim that anti-angiogenic agent is beneficial for cancer treatment. CONCLUSION: This review focuses on novel antiangiogenic agents that play a crucial role in controlling carcinogenesis.

Niosomes gel of apigenin to improve the topical delivery: development, optimization, ex vivo permeation, antioxidant study, and in vivo evaluation.

Niosomes (NS) are the promising and novel carrier of the drug for effective transdermal delivery. Apigenin (AN) is a natural bioactive compound and has various pharmacological activities. AN is poorly water soluble which directly affects therapeutic efficacy. The aim of this research work was to develop the AN-NS gel to improve transdermal delivery. The thin-film hydration method was used for the development of AN-NS. The optimized AN-NS (AN-NS2) has a vesicle size of 272.56 ± 12.49 nm, PDI is 0.249, zeta potential is -38.7 mV, and entrapment efficiency of 86.19 ± 1.51%. The FTIR spectra of the AN-NS2 depicted that AN encapsulated in the NS matrix. AN-NS2 formulation was successfully incorporated into chitosan gel and evaluated. The optimized AN-NS2 gel (AN-NS2G4) has 2110 ± 14cps of viscosity, 10.40 ± 0.21g.cm/sec of spreadability, and 99.65 ± 0.53% of drug content. AN-NS2G4 displayed significantly (p < 0.05) higher AN released (67.64 ± 3.03%) than pure AN-gel (37.31 ± 2.87%). AN-NS2G4 showed the Korsmeyer Peppas release model. AN-NS2G4 displayed significantly (p < 0.05) higher antioxidant activity (90.72%) than pure AN (64.53%) at 300 µg/ml. AN-NS2G4 displayed significantly (p < 0.05) higher % inhibition of swelling than pane AN-gel in carrageenin-induced paw oedema in rats. The finding concluded that niosomes-laden gel is a good carrier of drugs to improve transdermal delivery and therapeutic efficacy.

Development of Soft Luliconazole Invasomes Gel for Effective Transdermal Delivery: Optimization to In-Vivo Antifungal Activity.

Luliconazole (LZ) is a good candidate for the treatment of fungal infection topically but has limitations, i.e., poor solubility and poor permeability to skin. Due to these limitations, multiple administrations for a long time are required to treat the inflection. The aim of the present study was to develop the invasomes (IVS) gel of LZ to improve the topical antifungal activity. The IVS was prepared by the thin-film hydration method and optimized by Box-Bhekhen design software. The optimized LZIVS (LZIVSopt) has 139.1 ± 4.32 nm of vesicle size, 88.21 ± 0.82% of entrapment efficiency, 0.301 ± 0.012 of PDI, and 19.5 mV (negative) of zeta potential. Scanning microscopy showed a spherical shape of the vesicle. FTIR spectra showed there is no interaction between the drug and lipid. Thermogram showed that the LZ is encapsulated into the LZIVS matrix. LZIVSopt gel (LZIVSopt-G3) exhibited optimum viscosity (6493 ± 27 cps) and significant spreadability (7.2 g·cm/s). LZIVSopt-G3 showed 2.47-fold higher permeation than pure LZ-gel. LZIVSopt-G3 did not show any edema or swelling in the skin, revealing that the developed formulation is non-irritant. LZIVSopt-G3 exhibited significant inhibition of the fungus infection (C. albicans) in the infected rats. The finding concluded that IVS gel is a good carrier and an attractive approach for the enhancement of topical delivery of LZ to treat the fungal infection.

Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model.

Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER's antidepressant activity, a QER-loaded transferosome (QER-TFS) thermosensitive gel for intranasal administration was formulated and optimized. The therapeutic effectiveness of the optimized formulation was assessed in a depressed rat model by conducting a behavioral analysis. Behavioral study criteria such as immobility, swimming, climbing, sucrose intake, number of crossed lines, rearing, active interaction, and latency to feed were all considerably enhanced by intranasal treatment with the QER-TFS in situ gel in contrast to other formulations. A nasal histopathological study indicated that the QER-TFS thermosensitive gel was safe for the nasal mucosa. An immunohistochemical analysis showed that the animals treated with the QER-TFS thermosensitive gel had the lowest levels of c-fos protein expression, and brain histopathological changes in the depressed rats were alleviated. According to pharmacodynamic, immunohistochemical, and histopathological experiments, the intranasal administration of the QER-TFS thermosensitive gel substantially alleviated depressive symptoms in rats. However, extensive preclinical investigations in higher animal models are needed to anticipate its effectiveness in humans.

Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: I. Optimization, Characterization, Brain Localization, and Cytotoxic Studies.

Numerous neurological disorders have a pathophysiology that involves an increase in free radical production in the brain. Quercetin (QER) is a nutraceutical compound that shields the brain against oxidative stress-induced neurodegeneration. Nonetheless, its low oral bioavailability diminishes brain delivery. Therefore, the current study aimed to formulate QER-loaded transferosomal nanovesicles (QER-TFS) in situ gel for QER brain delivery via the intranasal route. This study explored the impacts of lipid amount, edge activator (EA) amount, and EA type on vesicle diameter, entrapment, and cumulative amount permeated through nasal mucosa (24 h). The optimum formulation was then integrated into a thermosensitive gel after its physical and morphological characteristics were assessed. Assessments of the optimized QER-TFS showed nanometric vesicles (171.4 ± 3.4 nm) with spherical shapes and adequate entrapment efficiency (78.2 ± 2.8%). The results of short-term stability and high zeta potential value (-32.6 ± 1.4 mV) of QER-TFS confirmed their high stability. Compared with the QER solution, the optimized QER-TFS in situ gel formulation exhibited sustained release behavior and augmented nasal mucosa permeability. CT scanning of rat brains demonstrated the buildup of gold nanoparticles (GNPs) in the brains of all treatment groups, with a greater level of GNPs noted in the rats given the transferosomal gel. Additionally, in vitro studies on PCS-200-014 cells revealed minimal cytotoxicity of QER-TFS in situ gel. Based on these results, the developed transferosomal nanovesicles may be a suitable nanocarrier for QER brain targeting through the intranasal route.

Development of Atomoxetine-Loaded NLC In Situ Gel for Nose-to-Brain Delivery: Optimization, In Vitro, and Preclinical Evaluation.

The present study investigates the brain-targeted efficiency of atomoxetine (AXT)-loaded nanostructured lipid carrier (NLC)-laden thermosensitive in situ gel after intranasal administration. AXT-NLC was prepared by the melt emulsification ultrasonication method and optimized using the Box-Behnken design (BBD). The optimized formulation (AXT-NLC) exhibited particle size PDI, zeta potential, and entrapment efficiency (EE) of 108 nm, 0.271, -42.3 mV, and 84.12%, respectively. The morphology of AXT-NLC was found to be spherical, as confirmed by SEM analysis. DSC results displayed that the AXT was encapsulated within the NLC matrix. Further, optimized NLC (AXT-NLC13) was incorporated into a thermosensitive in situ gel using poloxamer 407 and carbopol gelling agent and evaluated for different parameters. The optimized in situ gel (AXT-NLC13G4) formulation showed excellent viscosity (2532 ± 18 Cps) at 37 °C and formed the gel at 28-34 °C. AXT-NLC13-G4 showed a sustained release of AXT (92.89 ± 3.98% in 12 h) compared to pure AXT (95.47 ± 2.76% in 4 h). The permeation flux through goat nasal mucosa of AXT from pure AXT and AXT-NLC13-G4 was 504.37 µg/cm2·h and 232.41 µg/cm2·h, respectively. AXT-NLC13-G4 intranasally displayed significantly higher absolute bioavailability of AXT (1.59-fold higher) than intravenous administration. AXT-NLC13-G4 intranasally showed 51.91% higher BTP than pure AXT (28.64%) when administered via the same route (intranasally). AXT-NLC13-G4 showed significantly higher BTE (207.92%) than pure AXT (140.14%) when administered intranasally, confirming that a high amount of the AXT reached the brain. With the disrupted performance induced by L-methionine, the AXT-NLC13-G4 showed significantly (p < 0.05) better activity than pure AXT as well as donepezil (standard). The finding concluded that NLC in situ gel is a novel carrier of AXT for improvement of brain delivery by the intranasal route and requires further investigation for more justification.

Formulation Development, Optimization by Box-Behnken Design, and In Vitro and Ex Vivo Characterization of Hexatriacontane-Loaded Transethosomal Gel for Antimicrobial Treatment for Skin Infections.

There are many different infections and factors that can lead to skin illnesses, but bacteria and fungi are the most frequent. The goal of this study was to develop a hexatriacontane-loaded transethosome (HTC-TES) for treating skin conditions caused by microbes. The HTC-TES was developed utilizing the rotary evaporator technique, and Box-Behnken design (BBD) was utilized to improve it. The responses chosen were particle size (nm) (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (Y3), while the independent variables chosen were lipoid (mg) (A), ethanol (%) (B), and sodium cholate (mg) (C). The optimized TES formulation with code F1, which contains lipoid (mg) (A) 90, ethanol (%) (B) 25, and sodium cholate (mg) (C) 10, was chosen. Furthermore, the generated HTC-TES was used for research on confocal laser scanning microscopy (CLSM), dermatokinetics, and in vitro HTC release. The results of the study reveal that the ideal formulation of the HTC-loaded TES had the following characteristics: 183.9 nm, 0.262 mV, -26.61 mV, and 87.79% particle size, PDI, and entrapment efficiency, respectively. An in vitro study on HTC release found that the rates of HTC release for HTC-TES and conventional HTC suspension were 74.67 ± 0.22 and 38.75 ± 0.23, respectively. The release of hexatriacontane from TES fit the Higuchi model the best, and the Korsmeyer-Peppas model indicates the release of HTC followed a non-Fickian diffusion. By having a higher negative value for cohesiveness, the produced gel formulation demonstrated its stiffness, whereas good spreadability indicated better gel application to the surface. In a dermatokinetics study, it was discovered that TES gel considerably increased HTC transport in the epidermal layers (p < 0.05) when compared to HTC conventional formulation gel (HTC-CFG). The CLSM of rat skin treated with the rhodamine B-loaded TES formulation demonstrated a deeper penetration of 30.0 µm in comparison to the hydroalcoholic rhodamine B solution (0.15 µm). The HTC-loaded transethosome was determined to be an effective inhibitor of pathogenic bacterial growth (S. aureus and E. coli) at a concentration of 10 mg/mL. It was discovered that both pathogenic strains were susceptible to free HTC. According to the findings, HTC-TES gel can be employed to enhance therapeutic outcomes through antimicrobial activity.

Phenanthroindolizidine Alkaloids Secondary Metabolites Diversity in Medicinally Viable Plants of the Genus Tylophora.

Plants of the genus Tylophora have commonly been used in traditional medicine in various communities, especially in the tropical and subtropical regions of climatic zones. Of the nearly 300 species reported in the Tylophora genus, eight are primarily used in various forms to treat a variety of bodily disorders based on the symptoms. Certain plants from the genus have found use as anti-inflammatory, anti-tumor, anti-allergic, anti-microbial, hypoglycemic, hypolipidemic, anti-oxidant, smooth muscle relaxant, immunomodulatory, and anti-plasmodium agents, as well as free-radical scavengers. Pharmacologically, a few plant species from the genus have exhibited broad-spectrum anti-microbial and anti-cancer activity, which has been proven through experimental evaluations. Some of the plants in the genus have also helped in alcohol-induced anxiety amelioration and myocardial damage repair. The plants belonging to the genus have also shown diuretic, anti-asthmatic, and hepato-protective activities. Tylophora plants have afforded diverse structural bases for secondary metabolites, mainly belonging to phenanthroindolizidine alkaloids, which have been found to treat several diseases with promising pharmacological activity levels. This review encompasses information on various Tylophora species, their distribution, corresponding plant synonyms, and chemical diversity of the secondary metabolic phytochemicals as reported in the literature, together with their prominent biological activities.

Formulation of Miconazole-Loaded Chitosan-Carbopol Vesicular Gel: Optimization to In Vitro Characterization, Irritation, and Antifungal Assessment.

Miconazole nitrate (MN) is a poorly water-soluble and antifungal drug used for fungal infections. The present research work was designed to develop topical MN-loaded bilosomes (BSs) for the improvement of therapeutic efficacy. MZBSs were prepared by using the thin-film hydration method and further optimized by using the Box-Behnken statistical design (BBD). The optimized miconazole bilosome (MZBSo) showed nano-sized vesicles, a low polydispersity index, a high entrapment efficiency, and zeta potential. Further, MZBSo was incorporated into the gel using carbopol 934P and chitosan polymers. The selected miconazole bilosome gel (MZBSoG2) demonstrated an acceptable pH (6.4 ± 0.1), viscosity (1856 ± 21 cP), and spreadability (6.6 ± 0.2 cm2). Compared to MZBSo (86.76 ± 3.7%), MZBSoG2 showed a significantly (p < 0.05) slower drug release (58.54 ± 4.1%). MZBSoG2 was found to be a non-irritant because it achieved a score of zero (standard score) in the HET-CAM test. It also exhibited significant antifungal activity compared to pure MZ against Candida albicans and Aspergillus niger. The stability study results showed no significant changes after stability testing under accelerated conditions. MZ-loaded gels could serve as effective alternative carriers for improving therapeutic efficacy.

Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study.

Conventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90−95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be minimized by formulating a mucoadhesive ocular in-situ gel system that undergoes sol-gel transition upon stimulation by temperature, pH, and ions. The goal of this study was to develop ciprofloxacin (CIP) loaded bilosomes (BLO) in-situ gel for the improvement of therapeutic efficacy. The BLO was prepared by the thin-film hydration method and optimized by the Box−Behnken design. Cholesterol (CHO), surfactant (Span 60), and bile salt (sodium deoxycholate/SDC) were used as formulation factors. The vesicle size (nm) and entrapment efficiency (%) were selected as responses (dependent factors). The optimized CIP-BLO (CIP-BLO-opt) formulation displayed a vesicle size of 182.4 ± 9.2 nm, a polydispersity index of 0.274, a zeta potential of −34,461.51 mV, and an entrapment efficiency of 90.14 ± 1.24%. Both x-ray diffraction and differential scanning calorimetry spectra did not exhibit extensive peaks of CIP in CIP-BLO-opt, revealing that CIP is encapsulated in the BLO matrix. The CIP-BLO-opt formulation was successfully incorporated into an in-situ gel system using a gelling agent, i.e., Carbopol 934P and hydroxyl propyl methyl cellulose (HPMC K100 M). CIP-BLO-opt in-situ gel formulation (CIP-BLO-opt-IG3) was evaluated for gelling capacity, clarity, pH, viscosity, in-vitro CIP release, bio-adhesive, ex-vivo permeation, toxicity, and antimicrobial study. The CIP-BLO-opt-IG3 exhibited satisfactory gelling properties with a viscosity of 145.85 ± 9.48 cP in the gelling state. CIP-BLO-opt-IG3 displayed sustained CIP release (83.87 ± 5.24%) with Korsmeyer−Peppas kinetic as a best-fitted model (R2 = 0.9667). CIP-BLO-opt-IG3 exhibited a 1.16-fold than CIP-IG and a 2.08-fold higher permeability than pure CIP. CIP-BLO-opt-IG3 displayed a significantly greater bio-adhesion property (924.52 ± 12.37 dyne/cm2) than tear film. Further, CIP-BLO-opt-IG3 does not display any toxicity as confirmed by corneal hydration (76.15%), histology, and the HET-CAM test (zero scores). CIP-BLO-opt-IG3 shows significantly higher (p < 0.05) antimicrobial activity against P. aeruginosa and S. aureus than pure CIP. From all these findings, it could be concluded that CIP-BLO-opt-IG3 might be an effective strategy for the increment of corneal residence time and therapeutic activity of CIP.

Formulation of intranasal surface engineered nanostructured lipid carriers of rotigotine: Full factorial design optimization, in vitro characterization, and pharmacokinetic evaluation.

The objective of the present research was to develop, optimize, and evaluate rotigotine (RT)-loaded chitosan (CH) coated nanostructured lipid carriers (RT-CH-NLCs) for nose-to-brain delivery. The NLCs were prepared by homogenization and sonication technique as well as optimized by using three factors at three-level Box-Behnken design. The prepared NLCs were evaluated for particle size, zeta potential, entrapment efficiency, drug release, and ex vivo permeation. The pharmacokinetic study was conducted on albino Wistar rats to evaluate the bioavailability and neuropharmacokinetic parameters after intranasal administration of the optimized formulation (RT-CH-NLCs-OPT). The optimized formulation showed the particle size (170.48 ± 8.37 nm), PDI (0.19 ± 0.03), zeta potential (+26.73 mV), and entrapment efficiency (82.37 ± 2.48 %). In vitro drug release study displayed a sustained drug release pattern from RT-CH-NLCs-OPT (86.73 ± 8.58 % in 24 h) in comparison to RT-Dis (98.61 ± 7.24 % in 16 h). The permeability coefficient (PC) was found to be 11.39 ± 1.08 × 10-4 cm.h-1 and 2.34 folds higher than RT-Dis (4.85 ± 1.53 × 10-4 cm.h-1). The relative bioavailability of RT from RT-CH-NLCs-OPT was 3.2-fold greater as compared to RT-Dis. The absolute bioavailability of RT after intranasal administration of RT-CH-NLCs-OPT was 2.1-fold higher than RT-CH-NLCs-OPT administered intravenously. The brain targeting and targeting potential was displayed by DTE (422.03 %) and DTP (76.03 %) after intranasal administration of RT-CH-NLCs-OPT as compared to RT-Dis (DTE 173.91 % and DTP 59.97 %). Furthermore, confocal laser scanning microscopy results confirmed better brain targeting for RT-CH-NLCs-OPT as compared to RT-Dis. From these findings, it could be concluded that RT-CH-NLCs could serve as a promising strategy for targeting RT through the intranasal route.

Development of surface modified bilosomes for the oral delivery of quercetin: optimization, characterization in-vitro antioxidant, antimicrobial, and cytotoxicity study.

Quercetin (QT) is a flavonoid that exhibits anti-oxidant and chemo-preventive activity. This research work aimed to develop surface-modified bilosomes (BS) of QT. The BS was prepared by the solvent evaporation method and optimized by the Box-Behnken design. The optimized QT-BS (QT-BS3opt) displayed vesicle size (143.51 nm), PDI (0.256), zeta potential (-15.4 mV), and entrapment efficiency (89.52%). Further, the optimized QT-BS formulation was coated with chitosan (CS). The XRD diffractogram of CS-QT-BS3opt1 did not exhibit extensive peaks of QT, revealing that QT is properly encapsulated in the polymer matrix. The QT-BS3opt and CS-QT-BS3opt1 exhibited sustained-release (86.62 ± 3.23% and 69.32 ± 2.57%, respectively) up to 24 h with the Korsmeyer-Peppas kinetic model (R2 =0.9089). CS-QT-BS3opt1 exhibited significantly (P < .05) high flux, i.e. 4.20-fold more than pure QT dispersion and 1.27-fold higher than QT-BS3opt. CS-QT-BS3opt1 showed significantly greater bio-adhesion (76.43 ± 2.42%) than QT-BS3opt (20.82 ± 1.45%). The antioxidant activity showed that QT from CS-QT-BS3opt1 has more remarkable (P < .05) antioxidant activity at each concentration than pure QT. The CS-QT-BS3opt1 exhibited 1.61-fold higher cytotoxicity against MFC7 and 1.44-fold higher cytotoxicity against MDA-MB-231 than pure QT. The CS-QT-BS3opt1 displayed a significantly greater antimicrobial potential against E. coli than against S. aureus. From all these findings, it could be concluded that surface-modified QT-BS might be an effective approach for increasing the efficacy of QT in the treatment of certain ailments.

Harnessing Lipid Polymer Hybrid Nanoparticles for Enhanced Oral Bioavailability of Thymoquinone: In Vitro and In Vivo Assessments.

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.

EthoLeciplex: a new tool for effective cutaneous delivery of minoxidil.

This work designates EthoLeciplex, a vesicular system consisting of phospholipid, CTAB, ethanol and water, as an innovative vesicular system for cutaneous/transfollicular minoxidil (MX) delivery. MX-loaded EthoLeciplex was fabricated by one-step fabrication process. Formulations were designed to study the effects of drug/phospholipid ratio, CTAB/phospholipid ratio, and ethanol concentration on vesicular size, PDI, surface charge and EE%. The optimized formulation was characterized by in vitro release, drug/excipient compatibility, ex vivo skin permeability and safety. A size of 83.6 ± 7.3 to 530.3 ± 29.4 nm, PDI of 0.214 ± 0.01 to 0.542 ± 0.08 and zeta potential of +31.6 ± 4.8 to +57.4 ± 12.5 mV were observed. Encapsulation efficiency was obtained in its maximum value (91.9 ± 16.2%) at the lowest drug/phospholipid ratio, median CTAB/phospholipid and the highest ethanol concentration. The optimized formulation was consisted of 0.3 as drug/lipid ratio, 1.25 as CTAB/lipid ratio and 30% ethanol concentration and showed responses' values in agreement with the predicted results. Differential scanning calorimetry studies suggested that EthoLeciplex existed in flexible state with complete incorporation of MX into lipid bilayer. The cumulative amount of MX permeated from EthoLeciplex, conventional liposome and ethanolic solution after 12 h were 36.3 ± 1.5 µg/ml, 21 ± 2.0 µg/ml and 55 ± 4.0 µg/ml respectively. Based on the remaining amount, the amount of MX accumulated in different skin layers can be predicted in descending order as follows; EthoLeciplex > conventional liposome > MX solution. EthoLeciplex produced marked disorder in the stratum corneum integrity and swelling with no features of skin toxicity. This new cationic system is a promising carrier for cutaneous/transfollicular drug delivery.

Bilosomes as a promising nanoplatform for oral delivery of an alkaloid nutraceutical: improved pharmacokinetic profile and snowballed hypoglycemic effect in diabetic rats.

Diabetes mellitus is a life-threatening metabolic disease. At the moment, there is no effective treatment available to combat it. In this study, we aimed to develop berberine-loaded bilosomes (BER-BLS) to boost the oral bioavailability and therapeutic efficacy of berberine, a natural antidiabetic medication. The BER-BLS was fabricated using a thin-film hydration strategy and optimized using a central composite design (face-centered). The average vesicle size, entrapment efficiency, and surface charge of the optimized BER-BLS preparation were 196.5 nm, 89.7%, (-) 36.4 mV, respectively. In addition, it exhibited higher stability and better-sustained release of berberine than the berberine solution (BER-SOL). BER-BLS and BER-SOL were administered to streptozocin-induced diabetic rats. The optimized BER-BLS formulation had a significant hypoglycemic impact, with a maximum blood glucose decrease of 41%, whereas BER-SOL only reduced blood glucose by 19%. Furthermore, the pharmacological effect of oral BER-BLS and BER-SOL corresponded to 99.3% and 31.7%, respectively, when compared to subcutaneous insulin (1 IU). A pharmacokinetic analysis found a 6.4-fold rise in the relative bioavailability of berberine in BER-BLS when compared to BER-SOL at a dosage of 100 mg/kg body weight. Histopathological investigation revealed that BER-BLS is suitable for oral administration. Our data demonstrate that BLS is a potential nanocarrier for berberine administration, enhancing its oral bioavailability and antidiabetic activity.

Formulation and Evaluation of Moxifloxacin Loaded Bilosomes In-Situ Gel: Optimization to Antibacterial Evaluation.

In this study, moxifloxacin (MX)-loaded bilosome (BS) in situ gel was prepared to improve ocular residence time. MX-BSs were prepared using the thin-film hydration method. They were optimized using a Box−Behnken design (BBD) with bile salt (A, sodium deoxycholate), an edge activator (B, Cremophor EL), and a surfactant (C, Span 60) as process variables. Their effects were assessed based on hydrodynamic diameter (Y1), entrapment efficacy (Y2), and polydispersity index (Y3). The optimized formulation (MX-BSop) depicted a low hydrodynamic diameter (192 ± 4 nm) and high entrapment efficiency (76 ± 1%). Further, MX-BSop was successfully transformed into an in situ gel using chitosan and sodium alginate as carriers. The optimized MX-BSop in situ gel (MX-BSop-Ig4) was further evaluated for gelling capacity, clarity, pH, viscosity, in vitro release, bio-adhesiveness, ex vivo permeation, toxicity, and antimicrobial properties. MX-BSop-Ig4 exhibited an optimum viscosity of 65.4 ± 5.3 cps in sol and 287.5 ± 10.5 cps in gel states. The sustained release profile (82 ± 4% in 24 h) was achieved with a Korsmeyer−Peppas kinetic release model (R2 = 0.9466). Significant bio-adhesion (967.9 dyne/cm2) was achieved in tear film. It also exhibited 1.2-fold and 2.8-fold higher permeation than MX-Ig and a pure MX solution, respectively. It did not show any toxicity to the tested tissue, confirmed by corneal hydration (77.3%), cornea histopathology (no internal changes), and a HET-CAM test (zero score). MX-BSop-Ig4 exhibited a significantly (p < 0.05) higher antimicrobial effect than pure MX against Staphylococcus aureus and Escherichia coli. The findings suggest that bilosome in situ gel is a good alternative to increase corneal residence time, as well as to improve therapeutic activity.

Poly(N-isopropylacrylamide)-Based Hydrogels for Biomedical Applications: A Review of the State-of-the-Art.

A prominent research topic in contemporary advanced functional materials science is the production of smart materials based on polymers that may independently adjust their physical and/or chemical characteristics when subjected to external stimuli. Smart hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) demonstrate distinct thermoresponsive features close to a lower critical solution temperature (LCST) that enhance their capability in various biomedical applications such as drug delivery, tissue engineering, and wound dressings. Nevertheless, they have intrinsic shortcomings such as poor mechanical properties, limited loading capacity of actives, and poor biodegradability. Formulation of PNIPAM with diverse functional constituents to develop hydrogel composites is an efficient scheme to overcome these defects, which can significantly help for practicable application. This review reports on the latest developments in functional PNIPAM-based smart hydrogels for various biomedical applications. The first section describes the properties of PNIPAM-based hydrogels, followed by potential applications in diverse fields. Ultimately, this review summarizes the challenges and opportunities in this emerging area of research and development concerning this fascinating polymer-based system deep-rooted in chemistry and material science.

Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment.

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box−Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity.

Application of hydrophilic polymers for the preparation of tadalafil solid dispersions: micromeritics properties, release and erectile dysfunction studies in male rats.

The objective of the present study was to improve the dissolution rate and aphrodisiac activity of tadalafil by using hydrophilic polymers. Solid dispersions were prepared by solvent evaporation-Rota evaporator using Koliphore 188, Kollidon® VA64, and Kollidon® 30 polymers in a 1:1 ratio. Prepared tadalafil-solid dispersions (SDs) evaluated for yield, drug content, micromeritics properties, physicochemical characterizations, and aphrodisiac activity assessment. The optimized SDs TK188 showed size (2.175 ± 0.24 µm), percentage of content (98.89 ± 1.23%), yield (87.27 ± 3.13%), bulk density (0.496 ± 0.005 g/cm3), true density (0.646 ± 0.003 g/cm3), Carr's index (23.25 ± 0.81), Hausner ratio (1.303 ± 0.003) and angle of repose (<25°). FTIR spectrums revealed tadalafil doesn't chemically interact with used polymers. XRD and DSC analysis represents TK188 SDs were in the amorphous state. Drug release was 97.17 ± 2.43% for TK188, whereas it was 32.76 ± 2.65% for pure drug at the end of 2 h with 2.96-fold increase in dissolution and followed release kinetics of Korsmeyer Peppa's model. MDT and DE were noted to be 17.48 minutes and 84.53%, respectively. Furthermore, TK188 SDs showed relative improvement in the sexual behavior of the male rats. Thus the developed SDs TK188 could be potential tadalafil carriers for the treatment of erectile dysfunction.