The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

Antibacterial and antifungal activities of thymol: A brief review of the literature

Three-dimensional cell culture models, such as spheroids, can be used in the process of the development of new anticancer agents because they are able to closely mimic the main features of human solid tumors, namely their structural organization, cellular layered assembling, hypoxia, and nutrient gradients. These properties imprint to the spheroids an anticancer therapeutics resistance profile, which is similar to that displayed by human solid tumors. In this review, an overview of the drug resistance mechanisms observed in 3D tumor spheroids is provided. Furthermore, comparisons between the therapeutics resistance profile exhibited by spheroids, and 2D cell cultures are presented. Finally, examples of the therapeutic approaches that have been developed to surpass the drug resistance mechanisms exhibited by spheroids are described.

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs.

RxList

The number of animals used in research has increased with the advancement of research and development in medical technology. Every year, millions of experimental animals are used all over the world. The pain, distress and death experienced by the animals during scientific experiments have been a debating issue for a long time. Besides the major concern of ethics, there are few more disadvantages of animal experimentation like requirement of skilled manpower, time consuming protocols and high cost. Various alternatives to animal testing were proposed to overcome the drawbacks associated with animal experiments and avoid the unethical procedures. A strategy of 3 Rs (i.e. reduction, refinement and replacement) is being applied for laboratory use of animals. Different methods and alternative organisms are applied to implement this strategy. These methods provide an alternative means for the drug and chemical testing, up to some levels. A brief account of these alternatives and advantages associated is discussed in this review with examples. An integrated application of these approaches would give an insight into minimum use of animals in scientific experiments.

Alternatives to animal testing: A review.

The objective of this study was to synthesize and characterize citric acid crosslinked hydrogel films of carboxymethyl cellulose-tamarind gum for topical drug delivery. The hydrogel films were characterized by attenuated total reflectance-Fourier-transform infrared spectroscopy, solid state 13C-nuclear magnetic resonance spectroscopy and differential scanning calorimeter. The prepared hydrogel films were evaluated for the carboxyl content and equilibrium swelling ratio. Moxifloxacin hydrochloride was loaded into these hydrogel films and drug release was monitored in the phosphate buffer pH 7.4. Hemolysis assay was used to study biocompatibility of hydrogel films. Results of the attenuated total reflectance-Fourier-transform infrared spectroscopy, solid state 13C-nuclear magnetic resonance and differential scanning calorimeter confirmed the formation of citric acid-crosslinked hydrogel films. Total carboxyl content of hydrogel film was found to be increased when polymer ratio and amount of citric acid was increased. In contrast, swelling of hydrogel film was found to be decreased with increase in polymer ratio and amount of citric acid. Batch B1 showed highest drug loading with non-Fickian release mechanism. All remaining batches showed non-Fickian release behavior with diffusion coefficient greater than 0.5. Results of hemolysis assay indicated that the citric acid crosslinked carboxymethyl cellulose-tamarind gum hydrogels were safe to be used in drug delivery. These results indicated that the citric acid crosslinked carboxymethyl cellulose-tamarind gum composite hydrogel films has the potential to be used in topical novel drug delivery systems.

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Citric Acid Crosslinked Carboxymethyl Cellulose-based Composite Hydrogel Films for Drug Delivery

Synthesis and characterization of hydrogel films of carboxymethyl tamarind gum using citric acid.

Infections associated with the biofilms of Candida albicans are a challenge to antifungal treatment. Combinatorial therapy involving plant molecules with antifungal drugs would be an effective complementary approach against drug-resistant Candida biofilms. The aim of this study was to evaluate the efficacy of three bioactive terpenoids (carvacrol, eugenol and thymol) in combination with fluconazole against planktonic cells, biofilm development and mature biofilms of C. albicans. Activities of the selected molecules were tested using a microplate-based methodology, while their combinations with fluconazole were performed in a checkerboard format. Biofilms were quantitated by XTT-metabolic assay and confirmed by microscopic observations. Combinations of carvacrol and eugenol with fluconazole were found synergistic against planktonic growth of C. albicans, while that of thymol with fluconazole did not have any interaction. Biofilm development and mature biofilms were highly resistant to fluconazole, but susceptible to three terpenoids. Sensitization of cells by sub-inhibitory concentrations of carvacrol and eugenol resulted in prevention of biofilm formation at low fluconazole concentrations, i.e. 0.032 and 0.002 mg ml(-1), respectively. Addition of thymol could not potentiate activity of fluconazole against biofilm formation by C. albicans. Fractional inhibitory concentration indices (FICI) for carvacrol-fluconazole and eugenol-fluconazole combinations for biofilm formation were 0.311 and 0.25, respectively. The FICI value of 1.003 indicated a status of indifference for the combination of thymol and fluconazole against biofilm formation. Eugenol and thymol combinations with fluconazole did not have useful interaction against mature biofilms of C. albicans, but the presence of 0.5 mg ml(-1) of carvacrol caused inhibition of mature biofilms at a significantly low concentration (i.e. 0.032 mg ml(-1)) of fluconazole. The study indicated that carvacrol and eugenol combinations with fluconazole would be a potential alternative strategy for prevention and control of biofilm-associated C. albicans infections.

Shashikant C. Dhawale

Papers

Alternatives to animal testing: A review.

Citric Acid Crosslinked Carboxymethyl Cellulose-based Composite Hydrogel Films for Drug Delivery

Synthesis and characterization of hydrogel films of carboxymethyl tamarind gum using citric acid.

Sensitization of Candida albicans biofilms to fluconazole by terpenoids of plant origin.

Improvement in physicochemical properties of ezetimibe using a crystal engineering technique