Nanocomposite liposomes for pH-controlled porphyrin release into human prostate cancer cells

It is both challenging and desirable to have drug sensitizers released at acidic tumor pH for photodynamic therapy in cancer treatment. A pH-responsive carrier was prepared, in which fumed silica-attached 5,10,15,20-tetrakis(4-trimethylammoniophenyl)porphyrin (TTMAPP) was encapsulated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) nanocomposite liposomes. The sizes of agglomerates were determined by dynamic light scattering to be 115 nm for silica and 295 nm for silica-TTMAPP-DOPC liposomes. Morphological changes were also found in TEM images, showing liposome formation at pH 8.5 but collapse upon silanol protonation. TTMAPP release is enhanced from 13% at pH 7.5 to 80% at pH 2.3, as determined spectrophotometrically through dialysis membranes. Fluorescence emission of TTMAPP encapsulated in the dry film of liposomes was reduced to half at pH 8.6 when compared to that at pH 5.4, while the production of singlet oxygen was quintupled at pH 5.0 compared to pH 7.6. Upon treatment of human prostate cancer cells with liposomes containing 6.7 μM, 13 μM, 17 μM and 20 μM TTMAPP, the cell viabilities were determined to be 60%, 18%, 20% and 5% at pH 5.4; 58%, 30%, 25% and 10% at pH 6.3; and 90%, 82%, 68% and 35% at pH 7.4, respectively. Light-induced apoptosis in cancerous cells was only observed in the presence of liposomes at pH 6.3 and pH 5.4 but not at pH 7.4, as indicated by chromatin condensation.

Nanocomposite liposomes are relatively stable in weak basic solutions but effectively release porphyrins at acidic pH, as indicated by the difference in fluorescence.     

Barrier protection capacity of flip-top pharmaceutical vials

Study ObjectiveTo test the sterility of medication vial tops after removal of the dust cover, and to survey anesthesia providers for their perceptions surrounding medication vials and sterility.DesignExperimental design and survey instrument.SettingAmbulatory and hospital care setting.ParticipantsAnesthesia providers in the United States.MeasurementsA two-question survey was distributed to anesthesia providers in the U.S. An experimental model was conducted on a total of 42 medication vials. The access diaphragms of medication vials were sampled after routine handling, after exposure to aerosolized contamination with the dust cover on, and after submersion into a bacterial medium with the dust cover on.Main Results878 responses to Question 1 and 876 responses to Question 2 were received. Fifty-two percent of respondents declared that the access diaphragm was sterile in routine conditions, and 43% felt that (or were unsure if) the dust cover would prevent contamination when exposed to a contaminated environment. Two of the 12 vials sampled in the routine handling model had microbial contaminants on the access diaphragm. No growth was found on any of the 15 vials exposed to aerosolized E. coli. Seven of the 15 vials in the submersion model were contaminated.ConclusionsAnesthesia providers in the U.S. possess contradictory opinions of, and unclear knowledge about, the sterility of rubber stoppers used to access medications, and also the barrier capacity of a vial’s dust cover. Standard anesthetic medication vial dust covers do not offer barrier protection against the growth of pathogens.     

Influence of Bariatric Surgery on the Use and Pharmacokinetics of Some Major Drug Classes

The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes. Very few studies have been published on the influence of bariatric surgery on the pharmacokinetics of drugs. After bariatric surgery, theoretically, reduced drug absorption may occur. Correct dosing and choosing the right dosage form for drugs used by patients after bariatric surgery are necessary for optimal pharmacotherapy. Therefore, more clinical studies are needed on the influence of bariatric surgery on the pharmacokinetics of major drugs.