Current Drug Delivery - Volume 19, Issue 5, 2022

Background: Hydrophilic Hydroxypropyl Methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated. This study aims to investigate the release behaviors of both HPMC and paracetamol (model drug) from the hydrophilic matrix tablet. Methods: Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity: 4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w) of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-Nuclear Magnetic Resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness, front movement data,and distributive Near-Infrared (NIR) chemical imaging of HPMC in a matrix tablet during the dissolution process. Results: High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC. Conclusion: The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release- modulating mechanism in the hydrophilic matrix system.

Introduction: The pleiotropic effects of statins are recently explored for wound healing through angiogenesis and lymph-angiogenesis that could be of great importance in diabetic wounds. Aims: The aim of the present study is to fabricate nanofilm embedded with simvastatin-loaded chitosan nanoparticles (CS-SIM-NPs) and to explore the efficacy of SIM in diabetic wound healing. Methods: The NPs, prepared via ionic gelation, were 173 nm ± 2.645 in size with a zeta potential of -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into the polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats. Results: The results showed a significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site. Conclusion: Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.

Background: The increasing interest in using natural bioactive compounds as new drug candidates due to their low solubility led to designing and developing novel drug delivery systems. Out of those, orally disintegrating films (ODFs) are a very eminent drug delivery system among pediatrics and geriatrics. Objective: In our study, the solvent casting method was used to prepare eggshell membrane-based and turmeric extract loaded orally disintegrating films. Methods: Characterization of the prepared films was done with FTIR, AFM, and SEM analysis. The release profile of the turmeric extract was determined and fitted to the mathematical models. Results: AFM results showed that the best interaction between components was achieved in Film 2. The highest cumulative release percentage was obtained for the film with 7.5% (w/w) turmeric extract (Film-2) as 41.98%, based on the HPLC measurements. The Higuchi model was the best-- fitted model for Film 2. Conclusion: In this study, SEP and CMCH were used for the first time as biopolymers to prepare the orally disintegrating film. Turmeric extract was successfully integrated into films prepared from SEP and CMCH.

The conventional anticancer chemotherapies not only cause serious toxic effects but also produce resistance in tumor cells exposed to long-term therapy. Usually, the selective killing of metastasized cancer cells requires long-term therapy with higher drug doses because the cancer cells develop resistance due to the induction of poly-glycoproteins (P-gps) that act as a transmembrane efflux pump to transport drugs out of the cells. During the last few decades, scientists have been exploring new anticancer drug delivery systems such as microencapsulation, hydrogels, and nanotubes to improve bioavailability, reduce drug-dose requirement, decrease multiple drug resistance, and save normal cells as non-specific targets. Hopefully, the development of novel drug delivery vehicles (nanotubes, liposomes, supramolecules, hydrogels, and micelles) will assist in delivering drug molecules at the specific target site and reduce undesirable side effects of anticancer therapies in humans. Nanoparticles and lipid formulations are also designed to deliver a small drug payload at the desired tumor cell sites for their anticancer actions. This review will focus on the recent advances in drug delivery systems and their application in treating different cancer types in humans.

Psoriasis is an autoimmune skin disorder that is characterised by chronic inflammation and erythematous scaly patches. It has a significant impact on the patient's quality of life and can cause psychological stress. There are several aspects that cause psoriasis, for instance, environmental issues, immune disorders, bacterial infections, and genetic issues. Plentiful therapeutic means or treatments are accessible, but not any of them can completely and effectively cure psoriasis without hindering patient compliance. Hence, it becomes challenging to discover a new drug moiety or any drug delivery method to cure psoriasis. Conventional treatment of psoriasis involves anti-inflammatory agents, immune suppressants, phototherapy, and biological treatment, which were given in different forms such as topical, oral, or systemic formulations, but these all were unsuccessful to accomplish complete reduction of psoriasis as well as causing adverse side effects. In terms of dose frequency, doses, efficacy, and side effects, nanotechnology-based new formulations are the most promising prospects for addressing the challenges and limits associated with present psoriasis formulations. Hence, our major goal of this review is to present various advanced nanotechnological approaches for the effective topical treatment of psoriasis. In short, nano-formulations continue to be formed as very promising modalities in the treatment of psoriasis as they suggest improved penetration, targeted delivery, increased safety, and efficacy.

Background: Cancer, which is defined as abnormal cell growth, is one of the biggest public health problems in the world. Natural compounds, such as polyphenols, are used as chemo- preventive and chemotherapeutic agents in different types of cancer owing to their antioxidant, antineoplastic, and cytotoxic properties. To improve their bioavailability and releasing behavior, hydrogel systems with high drug loadingg, stability and hydrophilic nature have been designed. Objective: We conducted the present study to investigate the anticancer effects of curcumin and chrysin loaded in the alginate-chitosan hydrogel on breast cancer (T47D) and lung cancer (A549). Methods: The curcumin-chrysin-loaded alginate-chitosan hydrogels were prepared through the ionic gelation mechanism utilizing CaCl2. The prepared hydrogels were studied by using the Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The MTT and DAPI staining assays were employed for cytotoxicity and apoptosis studies of curcumin-chrysin- loaded alginate-chitosan hydrogels. The effects of the curcumin-chrysin-loaded alginate-chitosan hydrogels on the cell cycle of cell lines T47D and A549 were also evaluated using the propidium iodide staining. Results: The curcumin-chrysin-loaded alginate-chitosan hydrogels could significantly (p<0.05) reduce the viability and induce apoptosis. Morover G2/M causes arrest of the cell cycle in both A549 and T47D cell lines. Conclusion: The alginate-chitosan hydrogels could work best as an enhanced anticancer drug delivery system.

Objective: Develop and assess a transdermal emulsion loaded with nanostructured lipid carriers for vitamin D3 supplementation. Methods: Vitamin D3 loaded nanostructured lipid carriers, produced via high shear homogenization and ultrasonication, were assessed for their particle size, distribution, morphology, zeta potential, entrapment efficiency, and cytotoxicity. They were incorporated into a transdermal vehicle, and the stability and ex vivo permeation were evaluated. Results: Spherical nanoparticles were developed with a particle size of 192.5 nm, a polydispersity index of 0.13, a zeta potential of -29.0 mV, and an entrapment efficiency of 99.75%. They were stable (particle size and distribution) for 15 days when stored in a refrigerator, and for 30 days at room temperature and 32°C. The nanoparticles decreased the drug cytotoxicity against fibroblasts, as shown by IC50 (nanoparticle: 32.48 μg mL⁻¹; vitamin D3: 16.73 μg mL⁻¹). The emulsion loaded with nanoparticles minimized the degradation of vitamin D3 when compared with the nanoparticle dispersion. Additionally, the emulsion provided the skin permeation of vitamin D3 following the recommended daily allowance. Conclusion: To the best of our knowledge, this is the first study to use nanostructured lipid carriers for transdermal delivery of vitamin D. The developed formulation is a promising strategy to overcome the vitamin D3 variable oral bioavailability. It also represents a comfortable route of administration; thus it could be beneficial for patients and clinicians. However, further studies are needed to allow the permeation of larger amounts of vitamin D3, and the combination of these nanoparticles with microneedles would be interesting.

Aim: Felodipine (FDP), an antihypertensive drug possesses low water solubility and extensive first-pass metabolism leading to poor bioavailability. This impelled us to improve its solubility, bioavailability, and pharmacodynamic properties through the Nanocrystal (NC) approach. Methods: FDP-NC were prepared with Poloxamer F125 (PXM) by the antisolvent precipitation method. The experimental setup aimed at fine-tuning polymer concentration, the proportion of antisolvent to solvent, and the duration of ultrasonication for NC formulation. Results: Optimized formulation was characterized for particle size, solubility, and PDI. Particle reduction of 74.96 times was achieved with a 9X solubility enhancement as equated to pure FDP. The morphology of NC was found to be crystalline through scanning electron microscopy observation. The formation of the crystal lattice in FDP-NC was further substantiated by the XRD and DSC results. Lowering of the heat of fusion of FDP-NC is a clear indication of size reduction. The stability studies showed no substantial change in physical parameters of the FDP-NC as assessed by particle size, zeta potential, and drug content. Conclusion: The crystalline nature and improved solubility of FDP-NC improve the dissolution profile and pharmacodynamic data. The stability study data ensure that FDP-NC can be safely stored at 25°C. It is revealed that FDP-NC had a better release profile and improved pharmacodynamic effects as evident from better control over heart rate than FDP.

Background: Etomidate is commonly used in the induction of anesthesia. We have previously confirmed that etomidate requirements are significantly reduced in patients with obstructive jaundice and that etomidate anesthesia during Endoscopic Retrograde Cholangiopancreatography (ERCP) results in more stable hemodynamics compared to propofol. The aim of the present study is to investigate whether obstructive jaundice affects the pharmacokinetics of etomidate in patients who underwent bile duct surgery. Methods: A total of 18 patients with obstructive jaundice and 12 non-jaundiced patients scheduled for bile duct surgery were enrolled in the study. Etomidate 0.333 mg/kg was administered by IV bolus for anesthetic induction. Arterial blood samples were drawn before, during, and up to 300 minutes after the bolus. Plasma etomidate concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A nonlinear mixed-effects population modeling approach was used to characterize etomidate pharmacokinetics. The covariates of age, gender, height, weight, Body Surface area (BSA), Body Mass Index (BMI), Lean Body Mass (LBM), Total Bilirubin (TBL), Alanine Aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), creatinine (CR), and blood urea nitrogen (BUN) were tested for significant effects on parameters using a multiple forward selection approach. Covariate effects were judged based on changes in the Objective Function Value (OFV). Results: A three-compartment disposition model adequately described the pharmacokinetics of etomidate. The model was further improved when height was a covariate of total clearance [Cl1=1.30+0.0232(HT-162), ΔOFV=-7.33; P<0.01)]. The introduction of any other covariates, including bilirubin and total bile acids, did not improve the model significantly (P>0.01). For the height of 162cm, the final pharmacokinetic parameter values were as follows: V1=1.42 (95% CI, 1.01-1.83, L), V2=5.52 (95% CI, 4.07-6.97, L), V3=63.9 (95% CI, 41.95-85.85, L),Cl1= 1.30 (95% CI, 1.19-1.41, L/min), Cl2= 1.21 (95%CI, 0.95-1.47, L/min), and Cl3=0.584 (95%CI, 0.95-1.21, L/min), respectively. Conclusion: A 3-compartment open model might best describe the concentration profile of etomidate after bolus infusion for anesthesia induction. The pharmacokinetics of etomidate did not change by the presence of obstructive jaundice.