With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future.
The clinical potential of naringenin (NRG) is compromised due to its poor aqueous solubility and low oral bioavailability. The study is aimed at addressing these issues by means of naringenin nanosuspensions (NRG-NS) formulated using polyvinylpyrrolidone (PVP K-90) as stabiliser via antisolvent sonoprecipitation method. Optimisation of sonication time, drug concentration and stabilisers was done based on particle size. Characterisation of pure NRG and NRG-NS was carried out by scanning electron microscopy, differential scanning calorimetry (DSC), x-ray powder diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR). In vitro dissolution, intestinal absorption by non-everted rat intestinal sac model and in situ single pass intestinal perfusion techniques were performed for further investigation. Nanosuspensions prepared using PVP K-90 lead to minimum particle size (117 ± 5 nm) with zeta potential of -14.6 ± 5.6 mV. The particle size was affected by increasing sonication time, concentration of stabiliser and drug. Nanosizing process converted the crystalline drug into amorphous form as predicted from DSC and XRD patterns. FTIR demonstrated the formation of hydrogen bonds between drug and polymer. NRG-NS displayed a higher dissolution amount (91 ± 4.4% during 60 min) compared to NRG powder (42 ± 0.41%). The apparent and effective permeability of NRG-NS was increased as compared to the pure NRG. The in vivo pharmacokinetics demonstrated that the C and AUC values of NRG-NS were approximately 2- and 1.8-fold superior than the pure drug. Hence, overall results confirmed nanosuspensions as promising approach for NRG delivery with high absorption in gastrointestinal tract, improved dissolution and oral bioavailability.
Background Zotepine (ZTP), an antipsychotic drug is well tolerated and particularly effective for treating negative symptoms of psychosis. But is limited by low oral bioavailability caused by substantial first pass metabolism and thereby less amount of drug reaches the brain due to blood brain barrier (BBB). Objectives Since ZTP displays dose dependent side effects, purpose of the contemporary study is to develop zotepine loaded nanosuspension (ZTP-NS) for increased brain targeting in rats at lower doses. Methods ZTP-NS is prepared by two techniques viz., sonoprecipitation (SP) and combination technique (high pressure homogenization preceded by precipitation) by employing various stabilizers. Optimized ZTP-NS was characterized for particle size, solid state, morphology and solubility. In vitro drug release of ZTP and formulations was conducted using Franz diffusion cell. Stability study was performed at different temperature conditions. Pharmacokinetic study was performed in Wistar rats to determine the bioavailability and brain distribution of ZTP after intra-nasal (IN) and intravenous (IV) administration. Histopathology of brain was done after repeated administration of IN ZTP dispersion and NS up to 14 days. Results The optimized ZTP-NS formulated with Pluronic F-127 (0.3%w/v), Hydroxypropyl methyl cellulose E15 (0.3%w/v) and soya lecithin (0.4%w/v) showed particle size of 519.26 ± 10.44 nm & 330.2 ± 12.90 nm and zeta potential of −21.7 ± 1.39 mV and − 18.26 ± 1.64 mV with sonoprecipitation and combination technique respectively. In vitro drug release was high (81.79 ± 3.23%) for ZTP-NS prepared by combination technique. Intranasal NS resulted in high brain concentrations of 8.6 fold (sonoprecipitation) and 10.79-fold hike in AUC 0-24h in contrast to intravenous ZTP solution. Histopathology results reveal no significant changes in brain microscopic images. Conclusion ZTP-NS was successfully developed, characterized and found that nanosuspension is a favorable approach for intranasal delivery of zotepine.
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