Hurdles in selection process of nanodelivery systems for multidrug-resistant cancer.

PURPOSE: Most of the nanomedicines for treatment of multidrug-resistant cancer do not reach Phase III trials and many are terminated or withdrawn or are in an indeterminate state since long without any study results being presented. Extensive perusal of nanomedicine development research revealed that one of the critical aspects influencing clinical outcomes and which requires diligent scrutiny is selection process of nanodelivery system. METHODS: Research papers and articles published on development of nanodelivery systems for treatment of multidrug-resistant cancer were analyzed. Observations and conclusions noted by these researchers which might shed some light on poor clinical performance of nanocarriers were collated and summarized under observation section. Further research articles were studied to find possible solutions which may be applied to these particular problems for resolving them. The inferences of these findings were composed in Result section. RESULT: Plausible solutions for the observed obstacles were noted as examples of novel formulations that can yield the following: better in vivo imaging, precise targeting and dosing of a specific site and specific cell type in a particular cancer, modulation of tumor surroundings, intonation of systemic effects and high reproducibility. CONCLUSION: The angle of approach to the development of best nanosystem for a specific type of tumor needs to be spun around. Some of these changes can be brought about by individual scientists, some need to be established by collated efforts of scientists globally and some await advent of better technologies. Regardless of the stratagem, it can be said decisively that the schematics of development phase need rethinking.

The influence of nutritional and environmental conditions on the accumulation of poly-beta-hydroxybutyrate in Bacillus mycoides RLJ B-017.

AIMS: To optimize the nutritional and environmental conditions for growth of and poly-beta-hydroxybutyrate (PHB) accumulation in Bacillus mycoides RLJ B-017. METHODS AND RESULTS: An isolate, identified as B. mycoides, was grown on different sources of carbon and nitrogen. Among these, sucrose, beef extract and di-ammonium sulphate were found to be the most suitable for growth and PHB accumulation. The overall maximum value of PHB (%) in cells, PHB yield (Yp/s) and productivities (Qp and qp) were 69.4 +/- 0.4% dry cell weight (DCW), 0.21 gp gS(-1), 0.104 +/- 0.012 gp l(-1) h(-1) and 0.03 gp gx(-1) h(-1), respectively when grown in a medium containing 20 gs l(-1) sucrose, supplemented with di-ammonium sulphate. The addition of beef extract increased the value of PHB (%) in cells, PHB yield and productivities by 17.58 +/- 0,3, 23.8, 19.23 +/- 0.3 and 13.8 +/- 0.2% , respectively. The overall maximum values of PHB (% DCW), PHB yield and productivities were obtained at pH 7.0 +/- 0 .1, temperature 30 +/- 0.5 degrees C, agitation 650 rev min(-1) and oxygen transfer rate 3.8 mmol O(2) l(-1) h(-1). CONCLUSIONS: Sucrose, glucose and fructose were found to be more suitable for cell growth and PHB accumulation, but sucrose was less expensive than glucose. Among the nitrogen sources, beef extract and di-ammonium sulphate promoted PHB synthesis. The accumulation of PHB was observed to be growth associated. SIGNIFICANCE AND IMPACT OF THE STUDY: Gram-positive bacteria have not been reported to accumulate large amounts of polyhydroxyalkanoate and hence have not been considered as potent candidates for industrial production. A number of Bacillus spp. have been reported to accumulate 9-44.5% DCW PHB. By comparison, Bacillus RLJ B-017 contained 69.4 +/- 0.4% DCW PHB. Therefore, this strain has been considered as a potent organism for industrial interest. A relatively high yield of PHB was obtained in this wild strain and PHB synthesis was independent of nutrient limitation. The conditions for the higher PHB yield and productivity will be optimized in the next phase using fed-batch culture.

Quinacrine sterilization in Tripura, India.

A 611-case clinical trial of quinacrine sterilization (QS) was conducted at Agartala, Tripura State, India, using a unique protocol. No pregnancy failures were reported after a mean of 45.8 months of follow-up. Three trans-cervical insertions of 324 mg, 288 mg, and 252 mg quinacrine pellets were used in the first, second, and third insertions, respectively. Insertions were done on Days 6-10 of the menstrual cycle with the women remaining in a slight Trendelenberg position for 2 h post insertion. Antibiotics were prescribed after each insertion, and 3 months' supply of an additional contraception provided from first insertion. A unique inducement to report pregnancy failures was employed. Each woman was offered the equivalent of 5 months' family income to report any pregnancy following QS and a free menstrual regulation procedure. No pregnancies were reported. An independent follow-up visit to a systematic sample of 40 women found no pregnancies.

Growth-associated production of poly-3-hydroxybutyrate by Bacillus mycoides.

Bacillus mycoides strain RIJ B-017, a growth-associated poly-3-hydroxybutyrate (PHB) producer was grown on sucrose-containing media. PHB accumulated in cells up to 72% of dry cell mass. The overall maximum value of PHB yield (Yp/s) and productivities (Qp and qp) 250 mgp/gs, 120 mgp L-1 h-1 and 30 mgp gx-1 h-1, respectively, were obtained at 15 g/L sucrose. Differential scanning calorimeter heating curve showed two peaks, one at 95.9 degrees C and another at 165.4 degrees C with a shoulder around 154.6 degrees C. The viscosity-average molar mass in chloroform at 27 degrees C was 505 kDa. The carbon content of PHB was 55.4% of the mass.