Liposomes- and ethosomes-associated distamycins: a comparative study.

The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration.

Attitudes of consumers and healthcare professionals towards the patient package inserts - a study in Palestine.

UNLABELLED: Reading the patient package inserts (PPIs) is a key source of information about medications for patients. They should be clear and understandable to the general population. OBJECTIVE: The aims of this study were to obtain base-line data on the extent of reading PPIs by consumers and possible factors that might affect this; to explore the attitude of the Palestinian public and healthcare professionals towards the patient package inserts (PPIs); and to review a random sample of PPIs for the availability of different information. METHODS: The first part of the study was a cross-sectional self-administered questionnaire. The questionnaire for consumers included 15 items. The questionnaire for healthcare professionals included 10 items and it was very similar to that of consumers with some modifications. In the second part, a random sample of PPIs was reviewed. In our community pharmacies, where medications are arranged according to their producing company, a researcher was asked to choose randomly 10-15 medications for every company to check for the availability of pharmacological, pharmaceutical and clinical information. RESULTS: A total of 304 healthcare professionals out of 320 (95.0%) and 223 consumers out of 240 (92.9%) accepted to answer the survey. Forty five percent consumers reported that they always read the PPIs, and 29.3% said that they read the PPIs most of the times. Increased rate of reading the leaflet was found among females (P = 0.047). The preferred language for the PPIs was Arabic for most of the consumers (89.6%) while it was English for most of the healthcare professionals (80.8%). 35.9% of the consumers and 43.6% of the healthcare professionals found the font size suitable. 42.3% of the consumers and 25.5% of the healthcare professionals said that they found the information in the PPIs useful and enough. The PPIs of 135 randomly sampled medications were reviewed. Many important sections were not found in the PPIs' sample. CONCLUSIONS: A high percentage of consumers read the PPIs, but still this needs to be improved. People would appreciate a more detailed and clear PPI. Pharmacists should advocate reading the PPIs but they need to provide consumers with detailed counseling to compensate for the missing information in some of the PPIs. Authorities and manufacturers should implement appropriate measures to regulate the quality and quantity of information in the PPIs.

Rational design, synthesis, and evaluation of key analogues of CC-1065 and the duocarmycins.

The design, synthesis, and evaluation of a predictably more potent analogue of CC-1065 entailing the substitution replacement of a single skeleton atom in the alkylation subunit are disclosed and were conducted on the basis of design principles that emerged from a fundamental parabolic relationship between chemical reactivity and cytotoxic potency. Consistent with projections, the 7-methyl-1,2,8,8a-tetrahydrocyclopropa[c]thieno[3,2-e]indol-4-one (MeCTI) alkylation subunit and its isomer 6-methyl-1,2,8,8a-tetrahydrocyclopropa[c]thieno[2,3-e]indol-4-one (iso-MeCTI) were found to be 5-6 times more stable than the MeCPI alkylation subunit found in CC-1065 and slightly more stable than even the DSA alkylation subunit found in duocarmycin SA, placing it at the point of optimally balanced stability and reactivity for this class of antitumor agents. Their incorporation into the key analogues of the natural products provided derivatives that surpassed the potency of MeCPI derivatives (3-10-fold), matching or slightly exceeding the potency of the corresponding DSA derivatives, consistent with projections made on the basis of the parabolic relationship. Notable of these, MeCTI-TMI proved to be as potent as or slightly more potent than the natural product duocarmycin SA (DSA-TMI, IC50 = 5 vs 8 pM), and MeCTI-PDE2 proved to be 3-fold more potent than the natural product CC-1065 (MeCPI-PDE2, IC50 = 7 vs 20 pM). Both exhibited efficiencies of DNA alkylation that correlate with this enhanced potency without impacting the intrinsic selectivity characteristic of this class of antitumor agents.