Secondary metabolites in topical infectious diseases and nanomedicine applications.

Topical infection affects nearly one-third of the world's population; it may result from poor sanitation, hygienic conditions and crowded living and working conditions that accelerate the spread of topical infectious diseases. The problems associated with the anti-infective agents are drug resistance and long-term therapy. Secondary metabolites are obtained from plants, microorganisms and animals, but they are metabolized inside the human body. The integration of nanotechnology into secondary metabolites is gaining attention due to their interaction at the subatomic and skin-tissue levels. Hydrogel, liposomes, lipidic nanoparticles, polymeric nanoparticles and metallic nanoparticles are the most suitable carriers for secondary metabolite delivery. Therefore, the present review article extensively discusses the topical applications of nanomedicines for the effective delivery of secondary metabolites.

RETRACTED: Alhakamy et al. Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells. Pharmaceutics 2020, 12, 761.

The journal retracts the article, "Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells" [...].

RETRACTED: Alhakamy et al. Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells. Pharmaceutics 2020, 12, 346.

The journal retracts the article, "Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells" [...].

RETRACTED: Alhakamy et al. Chitosan-Based Microparticles Enhance Ellagic Acid's Colon Targeting and Proapoptotic Activity. Pharmaceutics 2020, 12, 652.

The journal retracts the article "Chitosan-Based Microparticles Enhance Ellagic Acid's Colon Targeting and Proapoptotic Activity" [...].

Quercetin-Loaded Mesoporous Silica Nanoparticle-Based Lyophilized Tablets for Enhanced Physicochemical Features and Dissolution Rate: Formulation, Optimization, and In Vitro Evaluation.

Mesoporous silica nanoparticles (MSNPs) have been proposed as a potential approach for stabilizing the amorphous state of poorly water-soluble actives. This study aimed to improve the physiochemical characteristics of poorly water-soluble quercetin (QT) through a novel lyophilized formulation. Various parameters, including solvent polarity, QT-carrier mass ratio, and adsorption time, were studied to improve the loading of QT into MSNPs. The optimized loaded MSNPs were formulated into lyophilized tablets through a freeze-drying process using hydrophilic polyvinylpyrrolidone (PVP-K30) as a polymeric stabilizer and water-soluble sucrose as a cryoprotectant. The effect of PVP-K30 and sucrose on the particle size, disintegration time, friability, and time required to release 90% of QT were studied using 32 full factorial design. The optimized formula was characterized using different evaluating techniques; for instance, differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, drug content, moisture content, and saturation solubility. The analysis proved that QT was consistently kept in the nanosize range with a narrow size distribution. The loaded silica nanoparticles and the optimized formulation are in an amorphous state devoid of any chemical interaction with the silica matrix or the lyophilization excipients. The optimized formula also featured low friability (less than 1%), fast disintegration (< 30 s), and a pronounced enhancement in saturation solubility and dissolution rate. Briefly, we established that the lyophilized MSNPs-based tablet would be a potential strategy for improving the rate of dissolution and, ultimately, the bioavailability of the poorly water-soluble QT.

Fe(III)-Rhamnoxylan-A Novel High Spin Fe(III) Octahedral Complex Having Versatile Physical and Biological Properties.

An iron (III) complex with rhamnoxylan, a hemicellulose from Salvia plebeia seeds, was synthesized and characterized by elemental analysis, spectroscopic and magnetic susceptibility measurements, thermal analysis and scanning electron microscopy. The rhamnoxylan was found to be a branched hemicellulose consisting of ß-1,4-linked xylose main chain and rhamnose attached to the chain at ß-1,3 positions. The complex was found to contain 18.8% w/w iron. A high-spin octahedral geometry of Fe3+ was indicated by the electronic absorption spectrum of the complex. In other experiments, the complex exhibited good electrical and magnetic properties. In vivo efficacy, as hematinic, of the complex in induced anemia was demonstrated equivalent to that of iron protein succinylate (taken as standard) as evidenced by raised red blood cell count, hemoglobin, hematocrit and total iron in rabbit. The complex was found to be non-toxic with LD50 > 5000 mg kg−1 body weight in rabbit. Thus, iron(III)-rhamnoxylan hold the potential for application as hematinic for treatment of iron deficiency anemia.

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.

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.

Ibuprofen Loaded Electrospun Polymeric Nanofibers: A Strategy to Improve Oral Absorption.

The poor aqueous solubility of candidate drugs has presented a great challenge to formulation scientists for their effective oral delivery. Poor solubility is often associated with poor dissolution behavior and, subsequently, poor bioavailability for those drugs when intestinal absorption is dissolution rate limited. In the present study electrospun polymeric nanofibers were developed to address the poor aqueous solubility of ibuprofen, a Biopharmaceutic Classification System (BCS) class-II drug. Hydrophilic spinnable polymers like polyvinyl pyrrolidone were deployed as a carrier system for the fabrication of nanofibers. The electrospinning parameters like flow rate, voltage, and spinneret to collector distance were optimized. The fabricated ibuprofen-loaded nanofibers were characterized using scanning electron microscopy and differential scanning calorimetry. Drug release studies and ex vivo intestinal absorption studies were also carried out. The nanofiber-based platform significantly improved in vitro absorption of ibuprofen compared to pure ibuprofen crystals.

Synthesis and Characterization of Antibiotic-Loaded Biodegradable Citrate Functionalized Mesoporous Hydroxyapatite Nanocarriers as an Alternative Treatment for Bone Infections.

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to provide an alternative to currently available bone-infection treatments. Here we designed mesoporous hydroxyapatite nanocarriers functionalized with citrate (Ctr-mpHANCs). Amoxicillin (AMX) is used as a model drug to load in Ctr-mpHANCs, and the drug loading was more than 90% due to the porous nature of nanocarriers. Scanning electron microscopy shows the roughly spherical morphology of nanocarriers, and the DLS study showed the approximate size of 92 nm. The Brunauer-Emmett-Teller (BET) specific surface area and pore diameter was found to be about 182.35 m2/g and 4.2 nm, respectively. We noticed that almost 100% of the drug is released from the AMX loaded Ctr-mpHANCs (AMX@Ctr-mpHANCs) in a pH-dependent manner within 3 d and 5 d at pH 2.0 and 4.5, respectively. The sustained drug release behaviour was observed for 15 d at pH 7.4 and no RBCs hemolysis by AMX@Ctr-mpHANCs. The broth dilution and colony forming unit (CFU) assays were used to determine the antimicrobial potential of AMX@Ctr-mpHANCs. It was observed in both studies that AMX@Ctr-mpHANCs showed a significant reduction in the bacterial growth of S. aureus, E. coli, and P. aeruginosa as compared to Ctr-mpHANCs with no bacteria-killing. Thus, we proposed that Ctr-mpHANCs can be used as a drug carrier and a treatment option for bone infections caused by bacteria.

Assessment of Knowledge Regarding Safety Profile, Use, and Boxed Warnings of Fluoroquinolones Among Healthcare Professionals in Saudi Arabia: A Potential Implication for Drug Regulatory Authorities.

Background: Despite a series of "boxed warnings" (BWs) issued by the US Food and Drug Administration (FDA), fluoroquinolones (FQs) are among the most prescribed antibiotics across the world. Moreover, few studies demonstrated that BW of FQs had less or no impact on prescribing patterns among healthcare professionals (HCPs), which might be attributed to the lack of knowledge toward such warnings. Since FQs contribute to a major proportion of antimicrobial prescriptions in the Kingdom of Saudi Arabia (KSA), this study aimed to ascertain the extent of knowledge toward safety profile, use, and BW of FQs among HCPs working in the KSA. Methods: This cross-sectional study (May-August 2021) was conducted among HCPs working in KSA through a validated questionnaire. The HCPs were requested to identify the indications, adverse effects (AEs), and BW of FQs. The knowledge score (out of 40) was estimated among participants, and its association with demographics was ascertained through the chi-square test, Student's t-test, or Mann-Whitney U-test and one-way ANOVA, or Kruskal-Wallis test, where appropriate. Results: Of the 573 participants (age: 36.1 ± 10.6 years, men: 59.7%), 262 (45.8%) were prescribers reporting frequent use of ciprofloxacin, levofloxacin, and ofloxacin. One-fourth (25.6%) of the prescribers did not recognize nalidixic acid as an agent from FQs class. About 60% of participants correctly identified the mechanism of action of FQs. The average knowledge score was 14.8 ± 6.4, where only 21.5% of respondents scored ≥50%. The average knowledge score for indications, AEs, and BW domains was 5.29 ± 3.05, 6.17 ± 4.05, and 2.3 ± 1.5, respectively. Only 75 (13.1%) participants recognized half of the BW, and 38.6% of participants identified at least one warning. The HCPs aged >40 years (p = 0.043), having non-Saudi's nationality (p < 0.001), working in Riyadh and Eastern regions (p < 0.001), having pharmacy and medicine disciplines (p < 0.001), practicing in public sectors (p = 0.004), and having more than 10 years of experience (p < 0.001) were significantly associated with high knowledge score. Conclusion: This study demonstrates the unsatisfactory knowledge toward safety profile, use, and BW of FQs among HCPs which may put patients at increased risks of AEs. The knowledge score differed among various socio-demographic groups. There is a dire need to initiate the antimicrobial-focused educational campaigns among HCPs regardless of their specialties and methods to improve education and disseminate FDA warnings in practice.

Arabinoxylan-Carboxymethylcellulose Composite Films for Antibiotic Delivery to Infected Wounds.

Modern dressings should provide for local delivery of antibiotics and protect the wound from bacterial infection, dehydration and environmental factors to achieve optimal healing. The local delivery of antibiotics can reduce adverse effects and resistance challenges. In this study, we fabricated film dressings composed of arabinoxylan (AX) from Plantago ovata seed husks and carboxymethylcellulose (CMC) by a solvent cast method for the delivery of the antibiotic amikacin (AMK). To determine the suitability of the prepared AX-CMC composite films as wound dressings and drug delivery materials, their physical, chemical, mechanical, morphological, thermal, pharmaceutical, antimicrobial, cytocompatible, and drug delivery properties were investigated. The results demonstrated that the dressings were suitable for delivering the drug at the wound site in a sustained manner and keeping the environment moist for rapid healing. The AMK-loaded AX-CMC films exhibited controlled release of AMK, excellent antibacterial activity, and cytocompatibility. Thus, the AX-CMC composite films appear to be promising bioactive dressing materials for the prevention of wound infections.

Extraction and Characterization of Microcrystalline Cellulose from Lagenaria siceraria Fruit Pedicles.

Microcrystalline cellulose (MCC) is a versatile polymer commonly employed in food, chemical, and biomedical formulations. Lagenaria siceraria (bottle gourd) fruit is consumed in many parts of the world, and its pedicle is discarded as waste. In the quest for a novel renewable source of the MCC, the present study investigates the extraction and characterization of MCC from the pedicle of Lagenaria siceraria fruits. The MCC was extracted by sequentially treating pedicles with water, alkali, bleaching (sodium chlorite), and dilute sulfuric acid (acid hydrolysis). The removal of associated impurities from pedicle fibers was confirmed by Fourier transform infrared analyses. The extracted MCC exhibited a characteristic crystalline structure of cellulose in X-ray diffraction with a 64.53% crystallinity index. The scanning electron microscopy (SEM) showed the variation in the morphology of the fibers and the formation of MCC of approximately 100 µm. The thermogravimetric analysis (TGA) indicated higher thermal stability of MCC. MCC production from biowaste (pedicle) holds potential for application as an emulsifier, stabilizer, and thickener in the chemical, pharmaceutical, and food industries.

Impact of highly phospholipid-containing lipid nanocarriers on oral bioavailability and pharmacodynamics performance of genistein.

Oxidative stress is a leading cause of different diseases. Genistein is a valuable bioflavonoid possessing antioxidant and anti-inflammatory activity but unfortunately, it suffers from low aqueous solubility, extremely poor bioavailability and first pass effect when used in its pure state. The aim of this work was to formulate and characterize genistein-loaded highly phospholipid-containing lipid nanocarriers to improve oral bioavailability and pharmacodynamic performance. Lipid nanocarriers were prepared by the emulsification/sonication technique. The influence of phospholipid percentage (1%-10%) on physicochemical properties, drug release and stability was investigated. The particle size, zeta potential and EE% were in ranges from 211.9 ± 21.6 to 342.3 ± 7.9 nm, -11.6 ± 1.7 to -19.4 ± 3.1 mV and 78.5 ± 4.7% to 92.2 ± 1.9%, respectively. Drug release was less predominant in the case of SLN formulations when compared to corresponding NLC formulations. High phospholipid percentage produced less stable formulations in terms of particle size growth, gelation and heterogeneous particle distributions. DSC, FT-IR and XRD tools revealed that genistein has existed in an amorphous form in NLC4. The bioavailability of NLC4 was approximately 2.6-fold greater than that of conventional suspension. Additionally, lipid peroxidation in liver homogenate and histopathological alterations in liver and kidney sections were particularly improved, providing a promising strategy for oral administration of genistein.

Development and Characterization of Gentamicin-Loaded Arabinoxylan-Sodium Alginate Films as Antibacterial Wound Dressing.

Biopolymer-based antibacterial films are attractive materials for wound dressing application because they possess chemical, mechanical, exudate absorption, drug delivery, antibacterial, and biocompatible properties required to support wound healing. Herein, we fabricated and characterized films composed of arabinoxylan (AX) and sodium alginate (SA) loaded with gentamicin sulfate (GS) for application as a wound dressing. The FTIR, XRD, and thermal analyses show that AX, SA, and GS interacted through hydrogen bonding and were thermally stable. The AXSA film displays desirable wound dressing characteristics: transparency, uniform thickness, smooth surface morphology, tensile strength similar to human skin, mild water/exudate uptake capacity, water transmission rate suitable for wound dressing, and excellent cytocompatibility. In Franz diffusion release studies, >80% GS was released from AXSA films in two phases in 24 h following the Fickian diffusion mechanism. In disk diffusion assay, the AXSA films demonstrated excellent antibacterial effect against E.coli, S. aureus, and P. aeruginosa. Overall, the findings suggest that GS-loaded AXSA films hold potential for further development as antibacterial wound dressing material.

Formulation of Self-Nanoemulsifying Drug Delivery System of Cephalexin: Physiochemical Characterization and Antibacterial Evaluation.

A cephalexin (CEP) self-nanoemulsifying drug delivery system (SNEDDS) was developed in this study to improve the drug's oral administration. The CEP-SNEDDS was made utilizing an aqueous titration method employing Lauroglycol 90, Poloxamer 188, and Transcutol-HP. Box-Behnken design (BBD) with three factors at three levels was used for optimization, and their impacts on globule size (nm), transmittance (percent), and emulsification time (s) were assessed. The optimized formulation (Opt-F3) was further tested for zeta potential, refractive index, percent transmittance, thermodynamic stability, in-vitro release, ex vivo permeability, antibacterial activity, and bioavailability. The chosen formulation (Opt-F3) had a globule size of 87.25 ± 3.16 nm, PDI of 0.25, zeta potential of -24.37 mV, self-emulsification duration of 52 ± 1.7 s, and percentage transmittance of 99.13 ± 1.5%, viscosity of 96.26 ± 2.72 cp, and refractive index of 1.29 ± 0.1. It showed a sustained release profile (94.28 ± 5.92 percent in 24 h). The Opt-F3 formulation had 3.95 times the permeability of CEP-dispersion. In comparison to CEP-dispersion, it also demonstrated greater antibacterial efficacy against tested Gram-positive and Gram-negative pathogens. The oral bioavailability of Opt-F3 is 3.48 times higher than that of CEP-dispersion, according to an in-vivo investigation. It has been determined that the prepared CEP-SNEDDS may be an advantageous carrier for CEP delivery.

Development and Optimization of Nanolipid-Based Formulation of Diclofenac Sodium: In Vitro Characterization and Preclinical Evaluation.

In the present research study, we formulate bilosomes (BMs) of diclofenac (DC) for oral delivery for enhancement of therapeutic efficacy (anti-inflammatory disease). The BMS were prepared by thin film hydration method and optimized by Box−Behnken design (BBD) using cholesterol (A), lipid (B), surfactant (C), and bile salt (D) as formulation factors. Their effects were evaluated on vesicle size (Y1) and entrapment efficacy (Y2). The optimized DC-BMs-opt showed a vesicle size of 270.21 ± 3.76 nm, PDI of 0.265 ± 0.03, and entrapment efficiency of 79.01 ± 2.54%. DSC study result revealed that DC-BMs-opt exhibited complete entrapment of DC in BM matrix. It also depicted significant enhancement (p < 0.05) in release (91.82 ± 4.65%) as compared to pure DC (36.32 ± 4.23%) and DC-liposomes (74.54 ± 4.76%). A higher apparent permeability coefficient (2.08 × 10−3 cm/s) was also achieved compared to pure DC (6.6 × 10−4 cm/s) and DC-liposomes (1.33 × 10−3 cm/s). A 5.21-fold and 1.43-fold enhancement in relative bioavailability was found relative to pure DC and DC liposomes (DC-LP). The anti-inflammatory activity result showed a significant (p < 0.05) reduction of paw edema swelling compared to pure DC and DC-LP. Our findings revealed that encapsulation of DC in BMs matrix is a good alternative for improvement of therapeutic efficacy.

Surface-Modified Bilosomes Nanogel Bearing a Natural Plant Alkaloid for Safe Management of Rheumatoid Arthritis Inflammation.

Rheumatoid arthritis (RA) is a chronic inflammatory illness affecting the joints. The characteristic of RA is gradual joint deterioration. Current RA treatment alleviates signs such as inflammation and pain and substantially slows the progression of the disease. In this study, we aimed to boost the transdermal delivery of berberine (a natural product) by encapsulating it in chitosan, surface-modified bilosomes nanogel for better management of the inflammation of RA. The chitosan-coated bilosomes loaded with berberine (BER-CTS-BLS) were formulated according to the thin-film hydration approach and optimized for various causal variables, considering the effect of lipid, sodium deoxycholate, and chitosan concentrations on the size of the particles, entrapment, and the surface charge. The optimized BER-CTS-BLS has 202.3 nm mean diameter, 83.8% entrapment, and 30.8 mV surface charge. The optimized BER-CTS-BLS exhibited a delayed-release profile in vitro and increased skin permeability ex vivo. Additionally, histological examination revealed that the formulated BLS had no irritating effects on the skin. Furthermore, the optimized BER-CTS-BLS ability to reduce inflammation was evaluated in rats with carrageenan-induced paw edema. Our results demonstrate that the group treated with topical BER-CTS-BLS gel exhibited a dramatic reduction in rat paw edema swelling percentage to reach 24.4% after 12 h, which was substantially lower than other groups. Collectively, chitosan-coated bilosomes containing berberine have emerged as a promising therapeutic approach to control RA inflammation.

Preparation of NLCs-Based Topical Erythromycin Gel: In Vitro Characterization and Antibacterial Assessment.

In the present study, erythromycin (EM)-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification and ultra-sonication method. EM-NLCs were optimized by central composite design using the lipid (A), pluronic F127 (B) and sonication time (C) as independent variables. Their effects were evaluated on particle size (Y1) and entrapment efficiency (Y2). The optimized formulation (EM-NLCs-opt) showed a particle size of 169.6 ± 4.8 nm and entrapment efficiency of 81.7 ± 1.4%. EM-NLCs-opt further transformed into an in-situ gel system by using the carbopol 940 and chitosan blend as a gelling agent. The optimized EM-NLCs in situ gel (EM-NLCs-opt-IG4) showed quick gelation and were found to be stable for more than 24 h. EM-NLCs-opt-IG4 showed prolonged drug release compared to EM in situ gel. It also revealed significant high permeation (56.72%) and flux (1.51-fold) than EM in situ gel. The irritation and hydration study results depicted no damage to the goat cornea. HET-CAM results also confirmed its non-irritant potential (zero score). EM-NLCs-opt-IG4 was found to be isotonic and also showed significantly (p < 0.05) higher antimicrobial activity than EM in situ gel. The findings of the study concluded that NLCs laden in situ gel is an alternative delivery of erythromycin for the treatment of bacterial conjunctivitis.