Characterization and Bio-Evaluation of the Synergistic Effect of Simvastatin and Folic Acid as Wound Dressings on the Healing Process.

Wound healing is a significant healthcare problem that decreases the patient's quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.

Investigation of anti-PEG antibody response to PEG-containing cosmetic products in mice.

Polyethylene glycol (PEG), a polyether compound, is available in molecular weights from ∼300 g/mol to ∼10,000,000 g/mol. In the molecular weight range of ∼750 to ∼5000, PEG is commonly used in bioconjugation technology and nano-formulations to improve the circulation half-life of the formulations and increase their stability. In cosmetics, lower molecular weight PEG compounds such as PEG 60 or PEG 100 are widely used as emulsifiers and skin penetration enhancers. PEG polymers are generally recognized as biologically inert and non-immunogenic. However, it is recently reported that the "pre-existing" anti-PEG antibodies have been detected in high percentages of healthy individuals who have never received treatment with parenteral PEGylated formulations. To the best of our knowledge, we are the first to attempt to find an explanation for the source of pre-existing anti-PEG antibodies in healthy individuals. In a murine study, we demonstrated that topically applied PEG derivatives, present in two commercially available cosmetic products, could efficiently penetrate the stratum corneum and reach the systemic circulation. The skin penetration of PEG derivatives was further enhanced in injured or otherwise compromised skin. Daily application of cosmetic PEG derivatives primed the immune system, inducing anti-PEG IgM production. Anti-PEG IgM was detected by Day 14 in mice with normal skin, while anti-PEG IgM was detected as early as day 7 in mice with compromised skin. In addition, in mice with pre-induced circulating levels of anti-PEG IgM, topically applied PEG derivatives from cosmetic products appeared to bind to the pre-induced anti-PEG IgM, lowering blood levels. Current results indicate that PEG derivatives in cosmetic products may be an important contributor to the source of the "pre-existing" anti-PEG antibodies that have been detected in healthy individuals.

Brain Targeting of Citicoline Sodium via Hyaluronic Acid-Decorated Novel Nano-Transbilosomes for Mitigation of Alzheimer's Disease in a Rat Model: Formulation, Optimization, in vitro and in vivo Assessment.

Background: Alzheimer's disease (AD) is one of the furthermost advanced neurodegenerative disorders resulting in cognitive and behavioral impairment. Citicoline sodium (CIT) boosts the brain's secretion of acetylcholine, which aids in membrane regeneration and repair. However, it suffers from poor blood-brain barrier (BBB) permeation, which results in lower levels of CIT in the brain. Purpose: This study targeted to encapsulate CIT into novel nano-platform transbilosomes decorated with hyaluronic acid CIT-HA*TBLs to achieve enhanced drug delivery from the nose to the brain. Methods: A method of thin-film hydration was utilized to prepare different formulae of CIT-TBLs using the Box-Behnken design. The optimized formula was then hyuloranated via integration of HA to form the CIT-HA*TBLs formula. Furthermore, AD induction was performed by aluminum chloride (Alcl3), animals were allocated, and brain hippocampus tissue was isolated for ELISA and qRT-PCR analysis of malondialdehyde (MDA), nuclear factor kappa B (NF-kB), and microRNA-137 (miR-137) coupled with immunohistochemical amyloid-beta (Aß1-42) expression and histopathological finding. Results: The hyuloranated CIT-HA*TBLs formula, which contained the following ingredients: PL (300 mg), Sp 60 (43.97 mg), and SDC (20 mg). They produced spherical droplets at the nanoscale (178.94 ±12.4 nm), had a high entrapment efficiency with 74.92± 5.54%, had a sustained release profile of CIT with 81.27 ±3.8% release, and had ex vivo permeation of CIT with 512.43±19.58 µg/cm2. In vivo tests showed that CIT-HA*TBL thermogel dramatically reduces the hippocampus expression of miR-137 and (Aß1-42) expression, boosting cholinergic neurotransmission and decreasing MDA and NF-kB production. Furthermore, CIT-HA*TBLs thermogel mitigate histopathological damage in compared to the other groups. Conclusion: Succinctly, the innovative loading of CIT-HA*TBLs thermogel is a prospectively invaluable intranasal drug delivery system that can raise the efficacy of CIT in Alzheimer's management.

Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.

Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.

Tailoring of Selenium-Plated Novasomes for Fine-Tuning Pharmacokinetic and Tumor Uptake of Quercetin: In Vitro Optimization and In Vivo Radiobiodistribution Assessment in Ehrlich Tumor-Bearing Mice.

Quercetin (QRC) is a bioflavonoid with anti-inflammatory, antioxidant, and anticancer activities, yet QRC poor bioavailability has hampered its clinical implementation. The aim of the current work was to harness novasomes (NOVs), free fatty acid enriched vesicles, as a novel nano-cargo for felicitous QRC delivery with subsequent functionalization with selenium (SeNOVs), to extend the systemic bio-fate of NOVs and potentiate QRC anticancer efficacy through the synergy with selenium. QRC-NOVs were primed embedding oleic acid, Brij 35, and cholesterol adopting thin-film hydration technique according to Box-Behnken design. Employing Design-Expert® software, the impact of formulation variables on NOVs physicochemical characteristics besides the optimum formulation election were explored. Based on the optimal NOVs formulation, QRC-SeNOVs were assembled via electrostatic complexation/in situ reduction method. The MTT cytotoxicity assay of the uncoated, and coated nanovectors versus crude QRC was investigated in human rhabdomyosarcoma (RD) cells. The in vivo pharmacokinetic and biodistribution studies after intravenous administrations of technetium-99m (99mTc)-labeled QRC-NOVs, QRC-SeNOVs, and QRC-solution were scrutinized in Ehrlich tumor-bearing mice. QRC-NOVs and QRC-SeNOVs disclosed entrapment efficiency of 67.21 and 70.85%, vesicle size of 107.29 and 129.16 nm, ζ potential of -34.71 and -43.25 mV, and accumulatively released 43.26 and 31.30% QRC within 24 h, respectively. Additionally, QRC-SeNOVs manifested a far lower IC50 of 5.56 µg/mL on RD cells than that of QRC-NOVs (17.63 µg/mL) and crude QRC (38.71 µg/mL). Moreover, the biodistribution study elicited higher preferential uptake of 99mTc-QRC-SeNOVs within the tumorous tissues by 1.73- and 5.67-fold as compared to 99mTc-QRC-NOVs and 99mTc-QRC-solution, respectively. Furthermore, the relative uptake efficiency of 99mTc-QRC-SeNOVs was 5.78, the concentration efficiency was 4.74 and the drug-targeting efficiency was 3.21. Hence, the engineered QRC-SeNOVs could confer an auspicious hybrid nanoparadigm for QRC delivery with fine-tuned pharmacokinetics, and synergized antitumor traits.

Incorporating Gangliosides into PEGylated Cationic Liposomes that Complexed DNA Attenuates Anti-PEG Antibody Production but Not Anti-DNA Antibody Production in Mice.

Gangliosides (glycosphingolipids) reduce antibody production by inhibiting B-cell receptor (BCR) signaling. We have shown that a copresentation of gangliosides and polyethylene glycol (PEG) on the same liposomes suppresses anti-PEG IgM production in mice. In addition, we recently observed that pDNA incorporated in PEGylated cationic liposomes (PCLs) induces anti-DNA IgM, which could be a hurdle to the development of efficient gene delivery systems. Therefore, the focus of this study was to determine if the copresentation of gangliosides and DNA on the same PCL would suppress antibody production against DNA. PCLs including DNA induced both anti-PEG IgM production and anti-DNA IgM production. The extent of anti-PEG and anti-DNA IgM production was likely dependent on the immunogenicity of the complexed DNA. Treatment of clodronate-containing liposomes, which causes a depletion of phagocytic cells, suppressed anti-PEG IgM production from PCLs that did not include DNA but failed to suppress anti-PEG IgM production from PCLs that complexed DNA (PCLD). Both anti-PEG IgM and anti-DNA IgM was induced in T-cell-deficient nude mice as well as in normal mice following treatment with PCLs and PCLD, respectively. These results indicate that phagocytic cells contribute to anti-PEG IgM production but not to anti-DNA IgM production, while T-cells do not contribute to any form of antibody production. The copresentation of gangliosides and DNA significantly reduced anti-PEG IgM production but unfortunately did not reduce anti-DNA IgM production. It appears that the immunosuppressive effect of gangliosides, presumably via the CD22 signaling pathway, is limited only to anti-PEG immunity.

A Novel Nanoemulsion Intermediate Gel as a Promising Approach for Delivery of Itraconazole: Design, In Vitro and Ex Vivo Appraisal.

The aim the study was to design, formulate, and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of itraconazole for improving the topical antifungal properties of the drug by adopting the nanoemulsion intermediate gel of the optimized system. Solubility study was conducted to select the most appropriate oils and surfactants for formulation. Different possible systems were created. Ternary phase diagrams were constructed to select the most promising system for further study. The nanoemulsion intermediate gel of the selected system was evaluated for stability, dilution effect, viscosity, pH, antifungal activity, droplet size, PDI, and zeta potential. In vitro release of the drug from the selected intermediate gel was investigated, and the kinetic model of drug release was determined. Ex vivo permeation of itraconazole was studied, and the amount of drug accumulated in the skin was calculated. Solubility and phase diagrams revealed that the system consisting of 60% cotton seed oil and 40% span 80 provided the nanoemulsion intermediate gel with the highest drug concentration. The selected system had a droplet size of about 236 nm and zeta potential of - 59.8. The viscosity of the corresponding intermediate gel was 1583.47 cp. The system exhibited high stability at 4°C and 25°C for 12 months and improved antifungal activity. In vitro release study showed complete release of itraconazole within 4 h, while the ex vivo permeation study revealed accumulation of the majority of the drug within the skin layers (72.5%).

Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and in vivo evaluation in a rabbit ocular inflammatory model.

The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG-b-PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG-b-PLA micelles, respectively. The drug loading capacity was in the range of 6-12% and 15-25% for PEG-b-PCL and PEG-b-PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5- and 10-fold after loading into PEG-b-PCL and PEG-b-PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG-b-PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG-b-PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG-b-PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.

Oxiconazole nitrate solid lipid nanoparticles: formulation, in-vitro characterization and clinical assessment of an analogous loaded carbopol gel.

The aim of the present work was to develop a promising drug delivery system of oxiconazole nitrate-loaded solid lipid nanoparticles (SLNs) topical gel to enhance the drug effectiveness for the treatment of Tinea infection. SLNs were prepared by emulsification-solvent evaporation method. Particle size and entrapment efficiency of the prepared SLNs were investigated. An appropriate formulation was selected and examined for morphology and physicochemical characterization adopting Scanning electron microscope and Differential scanning colorimetry. In-vitro drug release was also investigated. The selected SLNs were loaded into 1% Carbopol 934 gel that was investigated for homogeneity, pH, grittiness, spreadability, viscosity and in vitro drug release. Clinical study for the developed gel system compared to the corresponding marketed product was conducted on 28 patients. The results revealed that the prepared oxiconazole nitrate SLNs had drug entrapment efficiency ranging from 41.34% to 75.07% and zeta potential lying between -13 and -50. Physicochemical characterization revealed a decrease in the drug crystallinity in the prepared SLNs. The gel formulation showed appropriate physical characteristics and sustained in-vitro drug release. Clinical study for the prepared oxiconazole nitrate SLNs gel showed significantly less side effects, better patient satisfaction and superior clinical improvement compared with the corresponding marketed product.

Real Life Egyptian Experience of Daclatasvir Plus Sofosbuvir with Ribavirin in Naïve Difficult to Treat HCV Patients.

BACKGROUND: Chronic infection with Hepatitis C virus (HCV) is considered as a major cause for developing liver cirrhosis and hepatocellular carcinoma. A new era in HCV treatment is ongoing using Direct Acting Antiviral activity (DAA). The first approved DAA drug was Sofosbuvir which has a high tolerability and preferable pharmacokinetic profile. Another recently developed drug is Daclatasvir a first-in-class HCV NS5A replication complex inhibitor. Both drugs are administered orally once daily and have potent antiviral activity with wide genotypic coverage. METHODS: In the outpatient clinic, one hundred and fifty naïve difficult to treat chronic HCV patients were recruited from Tropical Medicine Department at Fayoum public hospital. A combination of Daclatasvir (60 mg) and Sofosbuvir (400 mg) (DCV/SOF) has been administered for those patients once daily with Ribavirin (1200 mg or 1000 mg based on patients' weight on two divided doses) over a period of 12 weeks. All patients have been followed up for clinical, laboratory assessment and HCV PCR to detect the efficacy and safety of the therapy. RESULTS: Sustained Virologic Response rate (SVR12) was achieved in the vast majority of patients (90.67%). Cirrhotic patients showed lower SVR compared to non-cirrhotic patients (88.89% vs 90.91%, respectively). Around half of the patients (49.33%) developed adverse events (AEs) during treatment. The most common AEs were headache, fatigue and abdominal pain. CONCLUSION: The available evidence seems to suggest that combination therapy of (DCV/SOF with RBV) in the treatment of chronic HCV genotype IV naïve difficult to treat patients either cirrhotic or non-cirrhotic is safe and effective. Monitoring for clinical and laboratory hepatic parameters was the basis for these findings.

Best tigecycline dosing for treatment of infections caused by multidrug-resistant pathogens in critically ill patients with different body weights.

BACKGROUND: The intensive care unit (ICU) is a center of multidrug-resistant (MDR) pathogens. This is due to overuse of antibiotics in the treatment of critically ill patients. Tigecycline is a broad-spectrum antibiotic that belongs to the glycylcycline group. Tigecycline has been indicated in treatment of complicated intra-abdominal infections (cIAIs) and complicated skin and soft-tissue infections (cSSTIs). OBJECTIVE: This study was done to discover the best dose regimen of tigecycline in treatment of cSSTIs and cIAIs, especially in patients who are critically ill and obese, for clinical outcomes and safety. SETTING: The study was conducted in an adult ICU that consists of 25 beds in a general hospital and was conducted within 2 years. A total of 954 patients were screened in this study. METHODS: This was a retrospective cohort study that compared the clinical outcomes of patients: mortality, ICU stay, and safety of using two different dose regimens of tigecycline between patients with different body weight who were treated for infections caused by MDR pathogens in the ICU. The study was conducted within 2 years. All results were collected from patients' files and were analyzed with SPSS version 20. MAIN OUTCOME: The study was implemented to figure out the best dose regimen of tigecycline to achieve a reduction in mortality, ICU stay, treatment duration, and secondary septic-shock incidence with minimum side effects in treatment of cSSTIs and cIAIs in patients with different body weight. RESULTS: There was a significant improvement in mortality, ICU stay, recurrent infection by the same organism, duration of tigecycline treatment, number of patients who had first negative culture after starting treatment, secondary bacteremia, and secondary septic shock with patients who used high-dose regimens of tigecycline in different subgroups of body weight, with no significant difference in side effects. CONCLUSION: The use of high-dose tigecycline resulted in a significant enhancement in all clinical outcomes, especially mortality and ICU stay when used in treatment of overweight and obese patients with cSSTIs and cIAIs.

Extended infusion versus intermittent infusion of imipenem in the treatment of ventilator-associated pneumonia.

BACKGROUND: Mechanical ventilation support can be the main source of ventilator-associated pneumonia (VAP). VAP is a serious infection that may be associated with dangerous gram-negative bacteria mainly, and it leads to an increase in the mortality in the intensive care unit (ICU). Imipenem is one of the strongest antibiotics now available for treating VAP which is associated with gram-negative and gram-positive bacteria, and it belongs to beta-lactam antibiotic group (carbapenem). OBJECTIVE: This study tried to investigate the efficacy of imipenem against VAP when it was infused within 180 min versus the efficacy when it was infused within 30-60 min. SETTING: This study was conducted in main ICU in general hospital which consists of surgical and medical beds within 2 years. One hundred and eighty-seven patients were enrolled on it. METHOD: This study is a retrospective cohort which was conducted within 2 years. The efficacy of imipenem which was administered by intermittent infusion (30-60 min) within first year was compared with the efficacy of imipenem which was administered by extended infusion (180 min) within second year in the field of VAP curing and cost reduction. All data were collected retrospectively from patient medical files and were statistically analyzed by SPSS version 20. MAIN OUTCOME: The study was designed to measure clinical and cost reduction outcomes, mortality and hospital stay. RESULTS: The results indicated that there is a significant decrease in mortality, number of recurrent infection, and ICU stay length, and the number of mechanical ventilator days was associated with extended imipenem infusion during the second year of the study. CONCLUSION: The use of imipenem with extended infusion over 3 hours enhances its clinical outcomes in the treatment of VAP.

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies.

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using DSC and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. DSC and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. P188 modified the Tsol/gel of P407 bringing it close to eye temperature (35°C) compared with the formulation containing P407 alone. Moreover, gels that comprised P407 and P188 exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations PP11 and PP12, the work of adhesion decreased significantly (P<0.001) from 377.9±7.79mNmm to 272.3±6.11mNmm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control KT release as only 48% of the KT released within 12h. In addition, the HET-CAM and BCOP tests confirmed the non-irritancy of KT loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. MTT assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with KT showed reasonable and acceptable percent cell viability compared with control samples.

Flurbiprofen-loaded niosomes-in-gel system improves the ocular bioavailability of flurbiprofen in the aqueous humor.

The present work aimed to prolong the contact time of flurbiprofen (FBP) in the ocular tissue to improve the drug anti-inflammatory activity. Different niosome systems were fabricated adopting thin-film hydration technique and using the nonionic surfactant Span 60. The morphology of the prepared niosomes was characterized by scanning electron microscopy (SEM). Physical characterization by differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy were conducted for the optimized formula (F5) that was selected on the basis of percent entrapment efficiency, vesicular size and total lipid content. F5 was formulated as 1% w/w Carpobol 934 gel. Pharmacokinetic parameters of FBP were investigated following ocular administration of F5-loaded gel system, F5 niosome dispersion or the corresponding FBP ocular drops to albino rabbits dispersion. Anti-inflamatory effect of F5-loaded carbopol gel was investigated by histopathological examination of the corneal tissue before and after the treatment of inflamed rabbit eye with the system. Results showed that cholesterol content, surfactant type. and total lipid contents had an apparent impact on the vesicle size of the formulated niosomes. Physical characterization revealed reduced drug crystallinity and incidence of interaction with other niosome contents. F5-loaded gel showed higher Cmax, area under the curve (AUC0-12), and thus higher ocular bioavailability than those of the corresponding FBP ocular solution. F5-loaded gel showed a promising rapid anti-inflammatory effect in the inflamed rabbit eye. These findings will eradicate the necessity for frequent ocular drug instillation and thus, improve patient compliance.

Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for treatment of atopic dermatitis.

Silymarin is a naturally occurring flavonoid drug; evidence from recent research has highlighted its use as a potential treatment for atopic dermatitis (AD). Both poor water solubility and drug permeability have hindered the percutaneous absorption of silymarin. Formulation of silymarin into pluronic-lecithin organogel (PLO) basis for topical skin delivery is the main aim of this work. Six different PLO formulations were prepared containing various pluronic to lecithin ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide. Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for topical delivery of silymarin as it showed optimum pH, viscosity, drug content, and satisfactory in vitro silymarin permeation. The silymarin PLO formulation significantly relieved inflammatory symptoms of AD such as redness, swelling, and inflammation. These findings warrant the ability for application of these novel silymarin PLO formulations as a novel treatment for AD.

Optimisation of microstructured biodegradable finasteride formulation for depot parenteral application.

This study aimed to use the biocompatibility features of the biodegradable polymers to prepare depot injectable finasteride (FIN) microspheres for the treatment of benign prostatic hyperplasia. FIN microspheres were prepared utilising an emulsion-solvent evaporation/extraction technique. The Box-Behnken experimental design was adopted to optimise the preparation process. FIN plasma levels in albino rabbits were determined after injection with optimised FIN microspheres formula and compared with oral FIN suspension. Results revealed that the optimum microspheres displayed an amended sustained release pattern with lower initial burst. The cumulative FIN % released after 25 days was in the range 27.83-73.18% for F4 and F1, respectively. The optimised formula, with 50.0% (X1), and 22.316% (X2) and 1.38% (X3) showed 6.503 µm, 93.213%, 14.574%, and 64.838% for Y1, Y2, Y3, and Y4, respectively. In vivo studies displayed a sustained release pattern with minimal initial burst release when injected into rabbits.

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles.

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p < 0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT.

Improved corneal bioavailability of ofloxacin: biodegradable microsphere-loaded ion-activated in situ gel delivery system.

The aim of the study was to improve corneal penetration and bioavailability of ofloxacin (OFX) eye preparations. OFX was incorporated in poly (lactide-co-glycolide) as biodegradable microspheres using oil in oil emulsion solvent evaporation technique. The prepared OFX microspheres were then incorporated in Gelrite(®) in situ gel preparation. In addition, OFX Gelrite-based in situ gel formulations were prepared. OFX formulations were characterized for gelling capacity, viscosity, and rheological properties. Release studies for OFX microspheres, OFX in situ gel, and OFX-loaded microspheres in situ gel formulations were carried out to investigate release characteristics of the drug. The prepared OFX formulations were then investigated in vivo compared with commercially available OFX eyedrops. Results showed that the optimum Gelrite concentration was at 0.4%-0.7% w/v; the prepared formulations were viscous liquid transformed into a pourable gel immediately after the addition of simulated tear fluid with a gelling factor of 27-35. Incorporation of OFX-loaded microspheres in Gelrite solution (0.4% w/v) significantly altered the release profiles of OFX-loaded microspheres in situ gel formula compared with the corresponding OFX gels and OFX microspheres. In vivo results in rabbits showed that OFX-loaded microspheres in situ gel formula improved the relative bioavailability by 11.7-fold compared with the commercially available OFX eyedrops. In addition, the longer duration of action of OFX-loaded microspheres in situ gel formula preparations is thought to avoid frequent instillations, which improves patient tolerability and compliance.

Formulation and evaluation of meloxicam niosomes as vesicular carriers for enhanced skin delivery.

CONTEXT: Skin delivery of Meloxicam (MX) offers several advantages over the oral route which is associated with potential side effects. OBJECTIVES: The aim of this study was to develop transdermal MX in niosomes. MATERIALS AND METHODS: Vesicles prepared by thin film hydration method were characterized and the acute anti-inflammatory activity of 0.5% MX niosomal hydrogel was evaluated using carrageenan induced rat paw edema method. RESULTS: The results revealed that niosomes prepared from span 60 and cholesterol at 6:4 molar ratio using 20 mg of MX were of the highest entrapment efficiency (> 55%) and with particle size (187.3 nm). There was a marked increase in the percentage inhibition of edema in animals treated with MX vesicular gel compared to those treated with free MX and piroxicam gels. DISCUSSION: There was an inverse proportionality between vesicle size and cholesterol content. With increased cholesterol molar ratio the bilayer stability increased and permeability decreased leading to efficiently trapping the MX. In contrast, higher amounts of cholesterol may compete with the drug for packing space within the bilayer. The inhibitory effect of MX niosomal gel may be attributed to its superior skin permeation. CONCLUSIONS: The results suggest that niosomes may be promising vehicles for transdermal delivery of MX.