Cellulose-Derivatives-Based Hydrogels as Vehicles for Dermal and Transdermal Drug Delivery

The use of water-soluble polymers of natural, semisynthetic, and synthetic origin for dermal and transdermal drug delivery systems is manifold. Among the most used biopolymers in the formulation of skin preparations, the cellulose ether derivatives as representatives of semisynthetic polymers distinguish through their specific physicochemical properties, by which the pharmacist can select the appropriate cellulose derivative for a particular purpose. The hydrogels containing cellulose derivatives as gelling agents are widely used as water-soluble ointment bases, because they usually associate the characteristics of both conventional and innovative hydrogels, including especially safety, biocompatibility, biodegradability, and a relatively easy way of preparation and low price. The present chapter describes the following issues: the physicochemical properties of water-soluble cellulose derivatives in relationship with their type and grade; physical and chemical properties of cellulose-derivatives-based hydrogels and their compatibility with other auxiliary substances commonly used in the formulation of pharmaceutical hydrogels; the development and manufacturing of these hydrogels on both small and large scales; the characterization of cellulose derivatives hydrogels as pharmaceutical dosage forms through different compendial and noncompendial methods; and well-recognized and novel applications of cellulose-derivatives-based hydrogels for dermal and transdermal drug delivery

METALLOME OF ORIGANUM VULGARE: THE UNKNOWN SIDE OF A MEDICINAL AND AROMATIC PLANT USED WORLDWIDE

Abstract Potential health benefits of aromatic and medicinal plants connected to their content in minerals are usually not evoked by the relevant literature. However, they may be significant for persons using regularly phytotherapy, as well as for those adopting diets which are rich in herbal spices. In this context, we performed an extensive investigation of metal and metalloid elements present in different populations of wild-growing Origanum vulgare samples from Romania. Forty-nine elements were identified and quantified through inductively coupled plasma -mass spectrometry (ICP-MS). Results were discussed as to their significance for human health. The present study provides, for the first time, a complete set of reference data on the mineral content of Origanum vulgare from South-Western Romania. Rezumat Aportul elementelor minerale din plantele medicinale şi aromatice la menţinerea stării de sănătate este rareori abordată în literatura de specialitate. Totuși, această contribuţie ar putea fi semnificativă la persoanele care recurg în mod regulat la fitoterapie, precum şi la cele care adoptă o alimentaţie bogată în condimente vegetale. În acest context a fost realizată o analiză extensivă a elementelor metalice şi metaloizilor prezenţi în diferite populaţii de şovârf (Origanum vulgare) din flora spontană a României. Patruzeci şi nouă de elemente au fost identificate şi cuantificate prin inductively coupled plasma -mass spectrometry (ICP-MS). Rezultatele au fost analizate sub aspectul semnificaţiei lor pentru sănătatea umană. Prezentul studiu oferă, pentru prima dată, un set complet de date de referinţă pentru conţinutul în elemente minerale ale speciei Origanum vulgare din sud-vestul României

THE IMPACT OF HYPERTENSION AND ASSOCIATED COMORBIDITIES ON QUALITY OF LIFE ASSESSMENT QUESTIONNAIRE SF-36 V2

Abstract Hypertension is a common cardiovascular disease insufficiently treated and monitored due to nonspecific symptomatology. Untreated hypertension causes cardiovascular complications: coronary artery disease, heart failure or stroke which, alongside other comorbidities affect the patients' family, social and professional life Using SF-36 v2 quality of life assessment questionnaire, the present study aimed to analyze the influence the pathologies associated with hypertensive disease have on areas that make up its physical and psychosocial functions and its impact on patients' daily activities. This could help to improve the quality of health services in optimizing the adherence of the patients to the treatment. The study compared the quality of life indicators between the group of patients and a control group comprising healthy individuals. Comparing the scores obtained by the two groups, lower values in all subdomains were found for the study group compared with control group. The regression analysis showed that strong negative impact pathologies in all areas were heart failure, coronary heart disease, diabetes and anemia. The other pathologies differently influenced the physical and psychosocial functions. Rezumat Hipertensiunea arterială reprezintă patologia cardiovasculară cu incidenţa cea mai mare în populaţie datorită faptului că este insuficient tratată şi monitorizată. Netratată FARMACIA, 2013, Vol. 61, 3 504 cauzează complicaţii cardio-vasculare: boala coronariană, insuficienţă cardiacă, accidente vasculare ischemice care afectează pacientul din punct de vedere familial, social şi professional. Studiul de faţă a avut ca scop compararea şi interpretarea indicilor de calitate a vieţii între lotul de pacienţi şi un lot martor care cuprinde indivizi sănătoşi. S-a observat că, la lotul de pacienţi valorile tuturor scorurilor sunt inferioare celor de la lotul martor, iar analiza de regresie a demonstrat impactul negativ puternic pe care îl prezintă insuficienţa cardiacă, boala coronariană, diabetul şi anemia asupra indicilor de evaluare a calităţii vieţii. Scopul unei astfel de analize este acela de a ameliora calitatea vieţii pacienţilor prin optimizarea schemelor terapeutice şi îmbunătăţirea complianţei

Comprehensive Biosafety Profile of Carbomer-Based Hydrogel Formulations Incorporating Phosphorus Derivatives

Determining the safety of a newly developed experimental product is a crucial condition for its medical use, especially for clinical trials. In this regard, four hydrogel-type formulations were manufactured, all of which were based on carbomer (Blank-CP940) and encapsulated with caffeine (CAF-CP940), phosphorus derivatives (phenyl phosphinic (CAF-S1-CP940) and 2-carboxyethyl phenyl phosphinic acids (CAF-S2-CP940)). The main aim of this research was to provide a comprehensive outline of the biosafety profile of the above-mentioned hydrogels. The complex in vitro screening (cell viability, cytotoxicity, morphological changes in response to exposure, and changes in nuclei morphology) on two types of healthy skin cell lines (HaCaT—human keratinocytes and JB6 Cl 41-5a—murine epidermal cells) exhibited a good biosafety profile when both cell lines were treated for 24 h with 150 μg/mL of each hydrogel. A comprehensive analysis of the hydrogel’s impact on the genetic profile of HaCaT cells sustains the in vitro experiments. The biosafety profile was completed with the in vivo and in ovo assays. The outcome revealed that the developed hydrogels exerted good biocompatibility after topical application on BALB/c nude mice’s skin. It also revealed a lack of toxicity after exposure to the hen’s chicken embryo. Further investigations are needed, regarding the in vitro and in vivo therapeutic efficacy and safety for long-term use and potential clinical translatability

Topical Biocompatible Fluconazole-Loaded Microemulsions Based on Essential Oils and Sucrose Esters: Formulation Design Based on Pseudo-Ternary Phase Diagrams and Physicochemical Characterization

To initiate our research into the development of biocompatiîle gelled-microemulsions based on essential oils (EOs) and sucrose esters (SEs) for the topical delivery of fluconazole, this formulation study investigated the usefulness of two relatively harmless natural non-ionic surfactants from the group of SEs (sucrose laurate and stearate) to form, in the presence of antifungal EOs, stable, isotropic microemulsions effective on fluconazole solubilization. Fluconazole’s solubility in EO significantly depended on their chemical composition, showing higher values for cinnamon, oregano and clove essential oils, further selected as oil phase components for microemulsion formulations. The phase behavior of several EO–isopropyl miristate/SE–isopropanol/water systems was assessed through pseudo-ternary phase diagrams constructed by microplate dilution technique. The hydrocarbon chain length of the SE and EO type strongly influenced the size of the microemulsion region in the pseudo-ternary phase diagrams. Ten microemulsion formulations containing 2% fluconazole, 6% or 10% oil mixture of EO–isopropyl myristate in 1:1 ratio, 45% SE-isopropanol mixture and water, were selected and evaluated for physicochemical properties (droplet size, polydispersity, viscosity, refractive index, zeta potential and pH). All formulations were physicochemically acceptable, but viscosity enhancement and further in vitro and in vivo tests are required for the development of biocompatible, clinically safe and effective fluconazole topical preparations

Evaluation of phenolic profile, antioxidant and anticancer potential of two main representants of Zingiberaceae family against B164A5 murine melanoma cells

BACKGROUND: Curcuma longa Linnaeus and Zingiber officinale Roscoe are two main representatives ofZingiberaceae family studied for a wide range of therapeutic properties, including: antioxidant, anti-inflammatory, anti-angiogenic, antibacterial, analgesic, immunomodulatory, proapoptotic, anti-human immunodeficiency virus properties and anticancer effects. This study was aimed to analyse the ethanolic extracts of Curcuma rhizome (Curcuma longa Linnaeus) and Zingiber rhizome (Zingiber officinale Roscoe) in terms of polyphenols, antioxidant activity and anti-melanoma potential employing the B164A5 murine melanoma cell line. RESULTS: In order to evaluate the total content of polyphenols we used Folin-Ciocâlteu method. The antioxidant activity of the two ethanolic extracts was determined by DPPH assay, and for the control of antiproliferative effect it was used MTT proliferation assay, DAPI staining and Annexin-FITC-7AAD double staining test. Results showed increased polyphenols amount and antioxidant activity forCurcuma rhizome ethanolic extract. Moreover, 100 μg/ml of ethanolic plant extract from both vegetal products presented in a different manner an antiproliferative, respectively a proapoptotic effect on the selected cell line. CONCLUSIONS: The study concludes that Curcuma rhizome may be a promising natural source for active compounds against malignant melanoma

New, Biocompatible, Chitosan-Gelled Microemulsions Based on Essential Oils and Sucrose Esters as Nanocarriers for Topical Delivery of Fluconazole

Biocompatible gel microemulsions containing natural origin excipients are promising nanocarrier systems for the safe and effective topical application of hydrophobic drugs, including antifungals. Recently, to improve fluconazole skin permeation, tolerability and therapeutic efficacy, we developed topical biocompatible microemulsions based on cinnamon, oregano or clove essential oil (CIN, ORG or CLV) as the oil phase and sucrose laurate (D1216) or sucrose palmitate (D1616) as surfactants, excipients also possessing intrinsic antifungal activity. To follow up this research, this study aimed to improve the adhesiveness of respective fluconazole microemulsions using chitosan (a biopolymer with intrinsic antifungal activity) as gellator and to evaluate the formulation variables’ effect (composition and concentration of essential oil, sucrose ester structure) on the gel microemulsions’ (MEGELs) properties. All MEGELs were evaluated for drug content, pH, rheological behavior, viscosity, spreadability, in vitro drug release and skin permeation and antifungal activity. The results showed that formulation variables determined distinctive changes in the MEGELs’ properties, which were nevertheless in accordance with official requirements for semisolid preparations. The highest flux and release rate values and large diameters of the fungal growth inhibition zone were produced by formulations MEGEL-FZ-D1616-CIN 10%, MEGEL-FZ-D1216-CIN 10% and MEGEL-FZ-D1616-ORG 10%. In conclusion, these MEGELs were demonstrated to be effective platforms for fluconazole topical delivery

Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders