Safe Formulation Research Articles

A Review on Ocular Drug Delivery System

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. KEYWORDS: Cornea; Emulsions; Implants; Liposome; Nanomicelles;

Disclosing the Functional Potency of Three Oxygenated Monoterpenes in Combating Microbial Pathogenesis: From Targeting Virulence Factors to Chicken Meat Preservation.

During the last few decades, there has existed an increased interest in and considerable consumer preference towards using natural and safe compounds derived from medicinal plants as alternatives to synthetic preservatives to combat microbial pathogenicity. In this regard, the present study investigated the possible synergistic interactions of the anti-foodborne bacterial capacity of linalool (L), eucalyptol (E), and camphor (C). The antibacterial synergistic effect was determined against Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica Typhimurium, and Escherichia coli. The optimal predicted mixture showed the highest antibacterial activity at 33.5%, 33.2%, and 33.4% of L, E, and C, respectively. Molecular docking simulations displayed that the studied monoterpenes have effective antibacterial inhibitory effects by impeding specific virulence factors such as sortase A, listeriolysin O, L, D-Transpeptidase, and polyphosphate kinase. The selected triple combination of L, E, and C was applied as a natural preservative in minced chicken breast meat. In this regard, 1 MIC (16 µg/mL), 1.5 MIC (24 µg/mL), and 2 MIC (32 µg/mL) of L. monocytogenes were used, and the microbiological, physicochemical, and sensory analyses were monitored for 14 days of storage at 4 °C. The L/E/C mixture at different levels could delay lipid and protein oxidation, inhibit the microorganisms, and maintain the sensory attributes. Additionally, by using chemometric tools, strong connections between physicochemical properties, microbiological parameters, and organoleptic attributes were established. Concisely, this research confers the importance of the use of blended monoterpenes and highlights their antibacterial mode of action, effectiveness, and synergistic effects as a powerful and safe bio-preservative formulation in chicken meat products.

Evaluation of efficacy and safety profile of tadalafil 5 mg daily dose in the tablet form versus oral dispersible film in men with mild-to-moderate erectile dysfunction: a comparative placebo-controlled study

PurposeWe aimed to compare the efficacy, safety, and compliance of tadalafil 5 mg daily dose in the tablet form versus oral dispersible film (ODF) in men with mild-to-moderate erectile dysfunction (ED).MethodsOne hundred thirty-five randomized patients were equally divided into three groups according to age where each group included forty-five patients. Within each group, 15 patients received oral tadalafil 5 mg, 15 patients received ODF tadalafil 5 mg and 15 patients received a placebo once daily for 1 month. All participants were assessed by the validated Arabic version of the international index of erectile function (ArIIEF-5) at baseline and after 1 month. Also, the efficacy of different forms of tadalafil 5 mg was assessed by responding affirmatively to a questionnaire.ResultsPatients aged > 25 to < 40 years and 40–55 years and > 55 years showed a statistically significant improvement of ArIIEF-5 scores after tadalafil 5 mg tablet and ODF tadalafil 5 mg compared to placebo ODF (23 ± 1.4; 22.7 ± 0.9; 20 ± 0.9; 20.4 ± 1.3; 20.2 ± 1.2; 16.6 ± 1.2; 18.5 ± 1.7; 19.6 ± 1.4; 16.3 ± 1.4; p < 0.001, respectively). Three patients (> 25 to < 40 years) who received tadalafil 5 mg tablet showed muscle and back pain. Gastrointestinal (GIT) upset (eight patients) followed by headache (seven patients) were the main side effects reported in patients (40–55 years) who received tadalafil 5 mg tablet. While GIT upset was the main side effect reported in patients (> 55 years) who received tadalafil 5 mg tablet.ConclusionODF tadalafil 5 mg is an effective, tolerable, and safe formulation that can be used in patients with mild-to-moderate ED.

Investigation of in Vitro Immunostimulating Effects of FreezeThaw Antigens against Visceral Leishmaniasis Caused by L. Infantum

Background: Visceral leishmaniasis, also known as Kala-Azar among the public, is among the notifiable infectious diseases. The fact that an effective and safe drug or vaccine formulation suitable for use on humans has not been developed causes the disease threat to continue. The aim of this study is to determine the immune system stimulating properties and cytotoxicity of the formulations obtained by combining the antigen obtained from Leishmania infantum parasites with different adjuvants. Methods: L. infantum (EP 126) antigens were obtained by the freeze-thaw method. Freund's adjuvant (Complete and Incomplete), a classical adjuvant, was used in the studies. Mouse macrophage (J774) and mouse fibroblast (L929) cell lines were used for cytotoxicity studies. Additionally, the responses at both 10ug/ml and 40ug/ml were investigated to ensure that the developed formulations were easily adaptable to in vivo. While the cytotoxicity of the formulations was determined by the MTT cell viability analysis method, the antileishmanial property was determined by the Nitric Oxide (NO) determination method. Results: It was determined that all the developed formulations did not have a toxic effect on the host cell, the immunostimulating activity increased with increasing concentration, and the highest value was obtained at a concentration of 200 µg/ml. Cell viability at the maximum concentration was found to be between 78% and 89% for both J774 and L929 cells. The highest cell viability values and NO production abilities (37% increase compared to the control group) were obtained with Incomplete Freund's adjuvant (40 ug/ml formulation). Conclusion: It has been understood that the combination of antigens obtained by the freeze-thaw method with Freunds adjuvant (incomplete) supports NO production, thus having an immunostimulating effect.

Application of 3D printing technology for the development of dose adjustable geriatric and pediatric formulation of celecoxib

Developing safe and effective formulations for the geriatric and pediatric population is a challenging task due to issues of swallowability and palatability. The lack of standardized procedures for pediatric formulations further complicates the process. Manipulating adult formulations for children can lead to suboptimal efficacy and safety concerns. To overcome these challenges, minitablets or spinklets are preferred for the geriatric and pediatric population due to their smaller size and flexible dose adjustment. The aim of this study is the development of a 3D printed spinklets formulation of celecoxib, a nonsteroidal anti-inflammatory drug, using hot melt extrusion to address the limitations of traditional manufacturing methods. Three different formulations of celecoxib were prepared using Poly-2-ethyl-tetra-oxazoline (Aquazol) with and without surfactant. Subsequently, the mechanical properties and solubility of the drug-loaded filaments were evaluated. Solid state characterization confirmed the drug conversion into an amorphous form during the extrusion process, Computer-aided design software facilitate sprinklets design for fused deposition modeling and scanning electron microscopy assess the surface morphology. Sophorolipids plasticize better than TPGS, resulting in lowering processing temperatures during melt extrusion. In vitro drug release showed successful enhancements in the dissolution of oral medications for pediatric patients, considering their distinctive physiological characteristics. Overall, this study demonstrates the successful development of PEtOx-based 3D printed celecoxib sprinklets by coupling hot-melt extrusion and 3D printing technology. Future exploration holds the potential to revolutionize pharmaceutical production and advance personalized medication formulations.

Precise Therapy Using the Selective Endogenous Encapsidation for Cellular Delivery Vector System.

Interindividual variability in drug response is a major problem in the prescription of pharmacological treatments. The therapeutic effect of drugs can be influenced by human genes. Pharmacogenomic guidelines for individualization of treatment have been validated and used for conventional dosage forms. However, drugs can often target non-specific areas and produce both desired and undesired pharmacological effects. The use of nanoparticles, liposomes, or other available forms for drug formulation could help to overcome the latter problem. Virus-like particles based on retroviruses could be a potential envelope for safe and efficient drug formulations. Human endogenous retroviruses would make it possible to overcome the host immune response and deliver drugs to the desired target. PEG10 is a promising candidate that can bind to mRNA because it is secreted like an enveloped virus-like extracellular vesicle. PEG10 is a retrotransposon-derived gene that has been domesticated. Therefore, formulations with PEG10 may have a lower immunogenicity. The use of existing knowledge can lead to the development of suitable drug formulations for the precise treatment of individual diseases.

Accumulation of Iron Oxide-Based Contrast Agents in Rabbit Atherosclerotic Plaques in Relation to Plaque Age and Vulnerability Features.

In this study, a detailed characterization of a rabbit model of atherosclerosis was performed to assess the optimal time frame for evaluating plaque vulnerability using superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI). The progression of atherosclerosis induced by ballooning and a high-cholesterol diet was monitored using angiography, and the resulting plaques were characterized using immunohistochemistry and histology. Morphometric analyses were performed to evaluate plaque size and vulnerability features. The accumulation of SPIONs (novel dextran-coated SPIONDex and ferumoxytol) in atherosclerotic plaques was investigated by histology and MRI and correlated with plaque age and vulnerability. Toxicity of SPIONDex was evaluated in rats. Weak positive correlations were detected between plaque age and intima thickness, and total macrophage load. A strong negative correlation was observed between the minimum fibrous cap thickness and plaque age as well as the mean macrophage load. The accumulation of SPION in the atherosclerotic plaques was detected by MRI 24 h after administration and was subsequently confirmed by Prussian blue staining of histological specimens. Positive correlations between Prussian blue signal in atherosclerotic plaques, plaque age, and macrophage load were detected. Very little iron was observed in the histological sections of the heart and kidney, whereas strong staining of SPIONDex and ferumoxytol was detected in the spleen and liver. In contrast to ferumoxytol, SPIONDex administration in rabbits was well tolerated without inducing hypersensitivity. The maximum tolerated dose in rat model was higher than 100 mg Fe/kg. Older atherosclerotic plaques with vulnerable features in rabbits are a useful tool for investigating iron oxide-based contrast agents for MRI. Based on the experimental data, SPIONDex particles constitute a promising candidate for further clinical translation as a safe formulation that offers the possibility of repeated administration free from the risks associated with other types of magnetic contrast agents.

FORMULATION AND EVALUATION OF HERBAL GEL CONTAINING DIMOCARPUS LONGAN LOUR SEEDS EXTRACT FOR TREATMENT OF SKIN ACNE

The present research work focuses on skin acne with the aim of developing an effective and safe herbal gel using Dimocarpus longan Lour. The ethanol extract of Dimocarpus longanLour was incorporated into an optimized Carbopol gel base. Physical characterization and phytochemical testing of the extract have been carried out. Antimicrobial studies showed no detectable microbial contamination and demonstrated good areas of inhibition. Overall, this research report concludes that herbal gel formulation can provide effective and safe formulations leading to patient tolerance and treatment compliance.

TET1-Lipid Nanoparticle Encapsulating Morphine for Specific Targeting of Peripheral Nerve for Pain Alleviation.

Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia. To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA. Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine (p < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group (p < 0.0001). Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.

Investigation of the whitening activity of ginsenosides from Panax notoginseng and optimization of the dosage form

BackgroundGinsenoside, as an active ingredient in traditional Chinese medicine, has been widely used for skin whitening for several years. Recent research has found that Panax notoginseng has a higher content of ginsenosides compared with the Panax ginseng. Those ginsenosides have promising potential to be developed as skin whitening agents. MethodsWe selected five dammarane ginsenosides isolated from P. notoginseng and their mixtures to investigate the skin lightning activity. Zebrafish embryo model was used for initial screening of the whitening activity. Subsequently, the whitening effect of components was examined and compared via testing the inhibition of melanin and activity of tyrosinase in B16 cells treated with these components. Molecular docking was also applied to investigate the interactions between ginsenosides and tyrosinase. Finally, the most effective saponins were selected for dosage form optimization and the whitening effect of saponin-loaded ethosomes was further demonstrated on the C57BL/6 mouse model. ResultsExperimental results showed that the protopanaxtriol saponins (PTS) were the most potent saponins with a decent safety profile, and the molecule docking results demonstrated that PTS had strong inhibitory ability to tyrosinase. PTS was successfully encapsulated into ethosomes with an encapsulation efficiency of 93%. The PTS ethosome gel could effectively inhibit the melanin production caused by UVB tanning on the back skin of mice. ConclusionThe PTS ethosome gel provides an effective and safe formulation of PTS to whiten the UVB-tanned skin in vivo and could be used as a potential skin whitening agent in the future.

An innovative formulation approach for low-melting ingredients: optimizing an alternative melt suspension technique for Pyraclostrobin suspension concentrate

The agrochemical industry is now focusing more on safer formulations with lowest dose rate. Suspension Concentrate formulations are one of the safest and most commonly utilized type in agrochemical industry. In this study, a suspension concentrate was developed and compared using a novel melt suspension technique alongside the conventional milling process. The objective was to determine the effectiveness of the new technique in terms of particle size reduction, processing time, and storage stability. In the melt suspension process, the low melting active ingredient(fungicide), was melted along with suitable surfactants and antifreeze in water and homogenized at high rotation per minute (2000). The same fungicide suspension concentrate was also prepared using milling process for comparison. Stability studies were conducted following the Food and Agricultural Organization procedure for both suspensions concentrate products. The storage stability results showed that particle size variation was just 0.8 ± 0.84% (w/v), antifungal content variation during storage stability studies was (±3.12 g/L) only, all other physical parameters results variations were < ± 0.5% w/v. Prepared suspension concentrates were further analyzed using three analytical techniques, Ultraviolet-Visible spectroscopy, high-performance liquid chromatography, and Fourier-transform infrared spectroscopy. The study suggests that the melt suspension technique can be an alternative to the normal milling process for preparing stable suspension concentrate, particularly for low melting point compounds.

Interaction of Melatonin with Zwitterionic Model Lipid Membranes

Melatonin is a key hormone secreted by the pineal gland in the brain. It interacts strongly with cell membranes and plays a protective role in several diseases such as Alzheimer's disease, cardiovascular diseases, and cancer. Hence, studies on the interaction of melatonin with lipid bilayer membranes have gained importance. In this regard, the present study aims to analyze the influence of different concentrations (0 to 15 mol%) of melatonin on the thermal and structural properties of zwitterionic stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) lipid bilayer model systems by using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The DSC results have shown that melatonin interacts with the membrane in a concentration-dependent fashion, induces patch formation, and alters the phase behaviour by reducing the main phase transition temperature. FTIR data has shown that increasing the melatonin concentration caused a reduction in the wavenumber of C=O and PO$$_{2}^-$$ antisymmetric stretching vibrations corresponding to the ester carbonyl and phosphate groups of SOPC lipids. This indicates the possibility of strong hydrogen bonding of melatonin with the SOPC lipids and nearby water molecules in the environment, suggesting its preferential location near lipid heads at the interfacial region. These results help to understand the organization and interactions of melatonin with membranes and provide insights to develop safe melatonin-based formulations for pharmaceutical applications.

Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs.

Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs. To determine the potential for HCO-ethoxylate-containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO-25, -40, -60 and -80). Four healthy male laboratory dogs. We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre-treatment with an antihistamine. All HCO-ethoxylate-containing drugs caused a wheal-and-flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO-ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO-60-induced reaction was suppressed by an oral antihistamine. The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision-making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

Topical delivery of seriniquinone for treatment of skin cancer and fungal infections is enabled by a liquid crystalline lamellar phase

Seriniquinone (SQ) was initially described by our group as an antimelanoma drug candidate and now also as an antifungal drug candidate. Despite its promising in vitro effects, SQ translation has been hindered by poor water-solubility. In this paper, we described the challenging nanoformulation process of SQ, which culminated in the selection of a phosphatidylcholine-based lamellar phase (PLP1). Liposomes and nanostructured lipid carriers were also evaluated but failed to encapsulate the compound. SQ-loaded PLP1 (PLP1-SQ) was characterized for the presence of sedimented or non-dissolved SQ, rheological and thermal behavior, and irritation potential with hen's egg test on the chorioallantoic membrane (HET-CAM). PLP1 influence on transepidermal water loss (TEWL) and skin penetration of SQ was assessed in a porcine ear skin model, while biological activity was evaluated against melanoma cell lines (SK-MEL-28 and SK-MEL-147) and C. albicans SC5314. Despite the presence of few particles of non-dissolved SQ (observed under the microscope 2 days after formulation obtainment), PLP1 tripled SQ retention in viable skin layers compared to SQ solution at 12 h. This effect did not seem to relate to formulation-induced changes on the barrier function, as no increases in TEWL were observed. No sign of vascular toxicity in the HET-CAM model was observed after cutaneous treatment with PLP1. SQ activity was maintained on melanoma cells after 48 h-treatment (IC50 values of 0.59–0.98 µM) whereas the minimum inhibitory concentration (MIC) against C. albicans after 24 h-treatment was 32-fold higher. These results suggest that a safe formulation for SQ topical administration was developed, enabling further in vivo studies.

Assessment of KaraShieldTM properties in supporting the immune health of healthy subjects: a randomized, parallel, double-blind, placebo-controlled clinical study

Background: This study aims to investigate whether a novel herbal extract blend, KaraShieldTM could be used to help build a healthy immune system that could reduce the number of incidences or severity of common upper respiratory tract infections (URTIs). Methods: A randomized, parallel, double-blind, placebo-controlled clinical study of 60 days was done on 120 healthy subjects allocated to a treatment arm (500 mg/day, KaraShieldTM) or placebo arm (500 mg/day). Results: A 500 mg daily dosage of KaraShieldTM significantly improved the subjects' immune health as measured by parameters such as the frequency and severity of upper respiratory tract conditions, the serum IgG level, mean ISQ raw score, WURSS scale score, CRP level in the serum and WHOQOL-BREF score at the end of the study period of sixty days from the baseline compared to that of the placebo. The investigated product was found to be safe and well tolerated by the subjects. Conclusions: KaraShieldTM may represent a promising safe and effective formulation for building a healthy immune system that could then counteract URTIs.

Use of sisal industrial waste (Agave sisalana Perrine) in sustainable and multifunctional cosmetic products.

Sisal is a common stiff fibre produced around the world, corresponding to approximately 70% of the commercial production of all fibres of this type. The fibres are extracted from the leaves of Agave sisalana, from which approximately 4% of their weight is obtained, with the remaining 96% considered to be residues from the process of the sisal industry. The objective of this work was to obtain a polyphenol-enriched extract from the A. sisalana residue by ultrasonically assisted extraction, characterize it chemically, evaluate invitro antioxidant activity, and develop safe and stable photoprotective formulations for future application in cosmetic preparations. Ultrasonic extraction of solid plant material was performed using 50% ethanol/water (v/v). The extract was chemically characterized by high-performance liquid chromatography equipment associated with classical molecular networking and evaluated for invitro antioxidant activity by different methodologies. Ten formulations were prepared, varying the component concentrations and the shear time. The 1.0% sisal extract was incorporated into the most stable formulations, and preliminary and accelerated stability were evaluated. The emulsions were investigated for safety by assessment of primary accumulated dermal irritability and sensitization and a dermatological clinical study of phototoxicity and photosensitization. The photoprotective formulations containing or not containing the extract that were stable after 90 days had their invivo sun protection factor (SPF), UVA protection factor, critical wavelength, and protection against visible and blue light determined. Ultrasound extraction using 50% ethanol/water (EH 50) as an extractor vehicle showed the best yield. The extract exhibited a concentration of phenolic compounds (77.93 mg of equivalent to the standard gallic acid/g) and showed invitro antioxidant activity. Emulsions without and with 1.0% sisal extract remained stable and safe. The addition of the extract to the photoprotective formulation statistically increased the SPF when compared to the formulation without the extract and offered protection against UVA radiation, critical wavelengths, and absorption of visible and blue light. Based on the findings, the solid residue of A. sisalana may be indicated as a component of photoprotective and antioxidant cosmetic formulations.

Influence of sunscreen formulation on the transfer of mineral and organic ultraviolet filters from skin to seawater in simulated ocean bathing tests.

Significant research and regulatory attention have been focused on the potential for some ultraviolet filters (UVFs) to rinse off from beachgoers' skin into seawater leading to exposure to sea life, especially coral reefs. The amount of UVFs potentially rinsed from skin during recreational beach activities has not been well-studied, leading to uncertainty about the potential magnitude of aquatic UVF exposure due to changes in sunscreen use patterns. This study quantifies rinse-off of UVFs in sunscreen from skin into synthetic seawater and identifies differences in rinse-off quantity due to formulation type with a goal of informing future modeling efforts aimed at estimating UVF exposure to sea life associated with recreational activities at the beach. UVF rinse-off from skin during recreation in seawater was simulated by applying eight different sunscreen products to porcine skin samples followed by three periods of shaking in synthetic seawater totaling 40 minutes. The rinsed mass of six UVFs - zinc oxide, titanium dioxide, avobenzone, homosalate, octisalate, and octocrylene - was determined analytically in synthetic seawater and in extractant rinsate from glassware for organic UVFs and compared among formulas. Among the 22 UVF-formulation combinations tested, 19 resulted in less than 10% of the applied UVF rinsed from skin. All formulation-UVF combinations where the formula types were water-in-oil (reverse phase) emulsions or anhydrous resulted in 5% or less of the applied UVF rinsed to synthetic seawater. Sunscreens formulated as oil-in-water emulsions yielded higher rinse off percentages for all UVFs tested, with a maximum of 20% rinse-off of avobenzone in one lotion. The potential for sunscreen UVF rinse-off is significantly influenced by formulation and is generally well below the prior assumed rinse-off levels used to estimate risk. Formulation consideration is therefore essential for accurate exposure models used in environmental risk assessment. Anhydrous and reverse phase (water-in-oil) sunscreen formulations tested resulted in lower UVF transfer from skin to synthetic seawater in simulated ocean bathing tests and as a result, are expected to yield lower UVF exposures to sea life. This approach can be used in predictive environmental exposure models to support ecologically safe sunscreen formulation design.

Development and In-vitro Evaluation of Dexamethasone Enriched Nanoemulsion for Ophthalmic Indication

Background: Dexamethasone (DEX) is a glucocorticosteroid used in the treatment of steroid-responsive inflammatory conditions of the eye. The currently marketed formulations pose several issues, like poor drug residence time, resulting in frequent administration of the formulation, making them less effective. Objective: The present study aims to provide comprehensive data encompassing the designing, op-timization, development, and characterization of DEX nanoemulsion (DEX NE) for treating in-flammatory conditions of the anterior segment of the eye by employing the Quality by Design (QbD) approach. Methods: A Plackett-Burman Design (PBD) was employed to screen seven independent variables, such as oil concentration, surfactant concentration, polymer concentration, homogenization speed and time, microfluidization pressure and cycles, and their influence on critical quality attributes (CQAs), such as globule size, zeta potential, and viscosity, was evaluated. Furthermore, the Box-Behnken design (BBD) was employed for optimization, and design space was generated to obtain the optimized DEX NE. Results: The experimental results after DEX NE characterization reveal a globule size of 181 ± 90 nm with a zeta potential of -21.03 ± 1.68 mV and a viscosity of 19.99 cp. Furthermore, the drug re-lease study of simulated tear fluid demonstrated prolonged and steady release for up to 48 hr. Cyto-toxicity assay of DEX NE exhibited good cell viability. Conclusion: All these findings pave the way for a better understanding of developing a robust, safe, and non-toxic formulation for ocular drug delivery.

Development of chitosan based β-carotene mucoadhesive formulation for skin cancer treatment

Mucopermeating nanoformulations can enhance mucosal penetration of poorly soluble drugs at their target site. In this work, thiolated chitosan (TCS)-lithocholic acid (LA) nanomicelles loaded with β-carotene, a safe phytochemical with anticancer properties, were designed to improve the pharmaceutical and pharmacological drug profile. The TCS-LA nanomicelles were characterized by FTIR to confirm the presence of the thiol group that favors skin adhesion, and to corroborate the conjugation of hydrophobic LA with hydrophilic CS to form an amphiphilic polymer derivative. Their crystalline nature and thermal behavior were investigated by XRD and DSC analyses, respectively. According to DLS and TEM, their average size was <300 nm, and their surface charge was +27.0 mV. β-carotene entrapment and loading efficiencies were 64 % and 58 %, respectively. In vitro mucoadhesion and ex vivo mucopenetration analyses further corroborated the potential of the nanoformulation to deliver the drug in a sustained manner under conditions mimicking cancer micro-environment. Anticancer studies in mice demonstrated that the loaded nanomicelles delayed skin cancer growth, as revealed by both morphological and biochemical parameters. Based on the results obtained herein, it can be concluded that drug-loaded TCS-LA is a novel, stable, effective and safe mucoadhesive formulation of β-carotene for the potential treatment of skin cancer.

Dendrimer-conjugated isotretinoin for controlled transdermal drug delivery

BackgroundIn the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy.Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D).ResultsHerein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation.ConclusionOur findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders.Graphical