Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach.

Background: Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Methods: Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. Results: In this study, stearyl alcohol, oleic acid, Tween® 80 (polysorbate 80), and Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm2 and 12.3 ± 2.2 µg/cm2, while the commercial cream only deposited 1.0 ± 0.8 µg/cm2 and 1.5 ± 0.5 µg/cm2 of IMQ, respectively. Conclusion: In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.

pH and its applications in targeted drug delivery.

Physiologic pH is vital for the normal functioning of tissues and varies in different parts of the body. The varying pH of the body has been exploited to design pH-sensitive smart oral, transdermal and vaginal drug delivery systems (DDS). The DDS demonstrated promising results in hard-to-treat diseases such as cancer and Helicobacter pylori infection. In some cases, a change in pH of tissues or body fluids has also been employed as a useful diagnostic biomarker. This paper aims to comprehensively review the development and applications of pH-sensitive DDS as well as recent advances in the field.

3D printed bilayer mucoadhesive buccal film of estradiol: Impact of design on film properties, release kinetics and predicted in vivo performance.

Despite being an effective therapy for menopausal symptoms, the use of oral estrogen is associated with low bioavailability and serious adverse effects of venous thromboembolism. Individualized therapy has been recommended to maximize benefits and curb the adverse effects, but much has not been done in developing formulations that offer flexibility to personalize therapy. In the present study, we employed an innovative 3D printing technology to design and develop bi-layered estradiol film with different infill patterns with an aim of improving bioavailability and facilitating personalized treatment. Hydroxypropyl cellulose (HPC-H) based formulation exhibited suitable rheological properties and was used as a feedstock to fabricate estradiol films with different infill patterns namely honeycomb, rectangular and plain. The back layer was prepared from a hydroxyethyl cellulose-based formulation. The resulting films were subsequently characterized in terms of their physicochemical, mechanical, environmental impact, and release characteristics among others. Films with a plain infill pattern exhibited significantly higher % elongation break and tensile strength. The in vitro drug release study revealed the fastest drug release profile for rectangular infill (96 % within 4 h) and the slowest drug release was observed for the plain infill pattern (∼35 % within 4 h), highlighting the effect of the infill pattern on release kinetics. Films with honeycomb infill patterns were selected for further characterization based on mechanical and in vitro release properties. No interaction between components of the formulation was observed and the absence of crystallinity in the final product was confirmed by Differential Scanning Calorimetry (DSC) and X-Ray Powder Diffraction analyses (XRD). The force of adhesiveness for the film was 0.13 ± 0.03 N. The predicted AUC 0-4 h, Cmax, and Tmax were 144.85 ng·h/mL, 65.97 ng/mL, and 0.83 h for a film (honeycomb infill pattern) loaded with 1 mg of estradiol. The printing process of films with honeycomb and rectangular infill patterns was evaluated as "green" using the index of Greenness Assessment of Printed Pharmaceuticals (iGAPP) tool. Our finding demonstrates the development of bi-layered estradiol film using Pressure assisted microsyringe (PAM) 3D printing and the influence of infill patterns on release kinetics and mechanical properties. The fabricated film not only facilitates the move towards personalized medicine but could also improve the bioavailability of the drugs by bypassing the hepatic first-pass metabolism and decreasing wash-out by the saliva.

Incidence and predictors of surgical site infection in Ethiopia: prospective cohort.

BACKGROUND: Surgical site infections are commonest nosocomial infections and responsible for considerable morbidity and mortality as well as increased hospitalizations and treatment cost related to surgical operations. The aim of this study was to determine incidence and predictors of surgical site infections at surgical ward of Hawassa University Referral Hospital, Southern Ethiopia. METHODS: We performed prospective study involving 105 patients that undergone major surgical procedure at Hawassa University Referral Hospital from March 2 to May 2, 2015. Data were extracted from paper based medical charts, operational and anesthesia note, by direct observation and patients' interview. All patients were followed daily before, during and after operation for 30 days starting from the date of operation. Data were analyzed using Statistical Package for Social Science (SPSS) for window version 20.0 software. Predictors of Surgical site infections were identified using multivariable logistic regression model. P-value less than 0.05 was considered to be statistically significant. RESULT: We studied 105 patients. Sixty four patients (61%) were males. The mean age of the patients was 30.85 ± 17.72 years. The mean Body Mass Index (BMI) was 21.6 ± 4 kg/m2. Twenty patients (19.1%) developed surgical site infections. Age greater than 40 years, AOR = 7.7(95% CI [1.610-40.810 p = 0.016,]), preoperative hospital stay more than 7 days, AOR = 22.4(95% CI [4.544-110.780, p = 0.001]), duration of operation more than 1 hour, AOR = 8.01(95% CI [1.562-41.099, p = 0.013]) and administering antimicrobial prophylaxis before 1 hour of operation, AOR = 11.1 (95% CI [1.269-75.639, p = 0.014]) were independent predictors for surgical site infections. CONCLUSION: Surgical site infection is relatively high.