Transdermal delivery of tolterodine tartrate for overactive bladder treatment: In vitro, and in vivo evaluation

The purpose of the study was to develop a transdermal tolterodine tartrate (TT) patch and to analyse its efficacy for overactive bladder (OAB) treatment. Patches were prepared using various polymers and plasticizers via the solvent casting method. The patches were characterized for tensile strength, thickness, moisture content, modulus of elasticity and water absorption capacity. Differential scanning calorimetry and Fourier transform infrared analyses were also performed. To determine patch effectiveness, in vitro release, permeation and animal studies were performed. The patches showed satisfactory percentage of release, up to 89.9 %, and their mechanical properties included thickness (0.10–0.15 mm), tensile strength (4.62–9.98 MPa) and modulus of elasticity (20–29 MPa). There were no significant interactions between TT and other excipients. Animal studies indicated that the TT patch reduced the incidence of side effects; however, studies of longer duration are required to determine the effectiveness in treating OAB

Transdermal delivery of tolterodine tartrate for overactive bladder treatment: In vitro, and in vivo evaluation

The purpose of the study was to develop a transdermal tolterodine tartrate (TT) patch and to analyse its efficacy for overactive bladder (OAB) treatment. Patches were prepared using various polymers and plasticizers via the solvent casting method. The patches were characterized for tensile strength, thickness, moisture content, modulus of elasticity and water absorption capacity. Differential scanning calorimetry and Fourier transform infrared analyses were also performed. To determine patch effectiveness, in vitro release, permeation and animal studies were performed. The patches showed satisfactory percentage of release, up to 89.9 %, and their mechanical properties included thickness (0.10–0.15 mm), tensile strength (4.62–9.98 MPa) and modulus of elasticity (20–29 MPa). There were no significant interactions between TT and other excipients. Animal studies indicated that the TT patch reduced the incidence of side effects; however, studies of longer duration are required to determine the effectiveness in treating OAB

Development and In vitro Evaluation of Self-Adhesive Matrix-Type Transdermal Delivery System of Ondansetron Hydrochloride

Purpose: To develop and evaluate self-adhesive matrix-type ondansetron hydrochloride (OND) transdermal formulation.Methods: OND transdermal patches were prepared using solvent casting method. The matrix polymer composition was Eudragit E 100, polyvinyl pyrrolidone and either propylene glycol or dibutyl sebacate as plasticizer. Mean patch thickness, tensile strength, moisture content, water absorption capacity and drug content of the patches were studied. In vitro release and permeation of the patches were determined using Franz diffusion cell.Results: Mean patch thickness, moisture content, and water uptake increased with increased contents of polyvinyl pyrrolidone (PVP) and plasticiser. Higher levels of PVP and plasticiser increased drug release. Addition of release modifier such as succinic acid (SA) and myristic acid (MA) to the patch formulations produced a significant increase in drug release from the patch. Higuchi plots for patches containing propylene glycol (PG) were non-linear (r2 = 0.9564), indicating that they did not follow Higuchi release model whereas the plots for most of the patches containing dibutyl sebacate (DBS) followed Higuchi release model (r2 = 0.9974).Conclusion: DBS is a superior plasticiser to PG for OND matrix patches while succinic acid (SA) is a more effective release modifier than myristic acid (MA) for PG patches.Keywords: Ondansetron hydrochloride, Drug release, Release modifier, Transdermal, Dibutyl sebacate, Succinic acid, Higuchi model, Plasticize

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

Rajan Rajabalaya, Muhammad Nuh Musa, Nurolaini Kifli, Sheba R David PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Brunei Darussalam Abstract: Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. Keywords: liquid crystal, drug delivery, controlled release, lyotropic, surfactants, drug localizatio

Chitosan nanoparticle toxicity: A comprehensive literature review of in vivo and in vitro assessments for medical applications

Topic definition: This literature review aims to update the current knowledge on toxicity of chitosan nanoparticles, compare the recent findings and identify the gaps with knowledge that is present for the chitosan nanoparticles. Methods: The publications between 2010 and 2020 were searched in Science Direct, Pubmed.gov, Google Scholar, Research Gate, and ClinicalTrials.gov, according to the inclusion and exclusion criteria. 30 primary research studies were obtained from the literature review to compare the in vitro in vivo toxicity profiles among the chitosan nanoparticles. Major highlights: Chitosan nanoparticles and other types of nanoparticles show cytotoxic effects on cancer cells while having minimal toxicity on normal cells. This apparent effect poses some considerations for use in incorporating cancer therapeutics into chitosan nanoparticles as an administration form. The concentration, duration of exposure, and pH of the solution can influence nanoparticle cytotoxicity, particularly in zebrafish. Different cell lines exhibit varying degrees of toxicity when exposed to nanoparticles, and of note are liver cells that show toxicity under exposure as indicated by increased alanine transaminase (ALT) levels. Aside from ALT, platelet aggregation can be considered a toxicity induced by chitosan nanoparticles. In addition, zebrafish cells experience the most toxicity, including organ damage, neurobehavioral impairment, and developmental abnormalities, when exposed to nanoparticles. However, nanoparticles may exhibit different toxicity profiles in different organisms, with brain toxicity and liver toxicity being present in zebrafish but not rats. Different organs exhibit varying degrees of toxicity, with the eye and mouth apparently having the lowest toxicity, while the brain, intestine, muscles and lung showing mixed results. Cardiotoxicity induced by chitosan nanoparticles was not observed in zebrafish embryos, and nanoparticles may reduce cardiotoxicity when delivering drug. Toxicity found in an organ may not necessarily mean that it is toxic towards all the cells found in that organ, as muscle toxicity was present when tested in zebrafish but not in C2C12 myoblast cells. Some of the studies conducted may have limitations that need to be reconsidered to account for differing results, with some examples being two experiments done on HeLa cells where one study concluded chitosan nanoparticles were toxic to the cells while the other seems to have no toxicity present. With regards to LD50, one study has stated the concentration of 64.21 mg/ml was found. Finally, smaller nanoparticles generally exhibit higher toxicity in cells compared to larger nanoparticles. Scope for future work: This literature review did not uncover any published clinical trials with available results. Subsequent research endeavors should prioritize conducting clinical trials involving human volunteers to directly assess toxicity, rather than relying on cell or animal models

Medicinal Plants: A Potential Source of Compounds for Targeting Cell Division

Modern medicinal plant drug discovery has provided pharmacologically active compounds targeted against a multitude of conditions and diseases, such as infection, inflammation, and cancer. To date, natural products from medicinal plants remain a solid niche as a source from which cancer therapies can be derived. Among other properties, one favorable characteristic of an anticancer drug is its ability to block the uncontrollable process of cell division, as cancer cells are notorious for their abnormal cell division. There are numerous other documented works on the potential anticancer activity of drugs derived from medicinal plants, and their effects on cell division are an attractive and growing therapeutic target. Despite this, there remains a vast number of unidentified natural products that are potentially promising sources for medical applications. This mini review aims to revise the current knowledge of the effects of natural plant products on cell division

Development of controlled release silicone adhesive–based mupirocin patch demonstrates antibacterial activity on live rat skin against Staphylococcus aureus

Sheba R David,1 Nurafiqah Malek,1 Abdul Hanif Mahadi,2 Srikumar Chakravarthi,3 Rajan Rajabalaya1 1PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Bandar Seri Begawan, Brunei Darussalam; 2Centre for Advanced Material and Energy Sciences (CAMES), Universiti Brunei Darussalam, Bandar Seri Begawan, Brunei Darussalam; 3School of Medicine, Perdana University, Jalan MAEPS Perdana, Serdang, Selangor, Malaysia Background: Peritonitis is the most serious complication of peritoneal dialysis. Staphylococcus aureus infections could lead to peritonitis which causes reversal of peritoneal dialysis treatment back to hemodialysis. The aim of this study was to develop a controlled release silicone adhesive-based mupirocin patch for prophylactic effect and analyze its antibacterial effectiveness against S. aureus.Methods: The matrix patches were prepared by using different polymers, with and without silicone adhesive, dibutyl sebacate and mupirocin. The patches were characterized for mechanical properties, drug content, moisture content, water absorption capacity and Fourier transform infrared spectrum. In vitro release studies were performed by using Franz diffusion cell. In vitro disk diffusion assay was performed on the Mueller–Hinton Agar plate to measure the zone of inhibition of the patches. The in vivo study was performed on four groups of rats with bacterial counts at three different time intervals, along with skin irritancy and histopathologic studies. Results: The patches showed appropriate average thickness (0.63–1.12 mm), tensile strength (5.08–10.08 MPa) and modulus of elasticity (21.53–42.19 MPa). The drug content ranged from 94.5% to 97.4%, while the moisture content and water absorption capacities at two relative humidities (75% and 93%) were in the range of 1.082–3.139 and 1.287–4.148 wt%, respectively. Fourier transform infrared spectra showed that there were no significant interactions between the polymer and the drug. The highest percentage of drug release at 8 hours was 47.94%. The highest zone of inhibition obtained was 28.3 mm against S. aureus. The in vivo studies showed that the bacterial colonies were fewer at 1 cm (7×101 CFU/mL) than at 2 cm (1.3×102 CFU/mL) over a 24-hour period. The patches were nonirritant to the skin, and histopathologic results also showed no toxic or damaging effects to the skin. Conclusion: The in vitro and in vivo studies indicated that controlled release patches reduced the migration of S. aureus on the live rat skin effectively, however, a longer duration of study is required to determine the effectiveness of the patch on a suitable peritonitis-induced animal model. Keywords: transdermal delivery, matrix patch, peritonitis, antibacterial, dialysis infection, histopatholog

Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT) for the treatment of overactive bladder (OAB). Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE), vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%–91.68% and vesicle size was 253–845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB