MATERIALS & METHODS: F-BC-MTX-LPHNPs were fabricated using self-assembled nano-precipitation technique. Fructose was conjugated on the surface of the particles. The in vitro cytotoxicity, sub-cellular localization and apoptotic activity of F-BC-MTX-LPHNPs were evaluated against MCF-7 breast cancer cells. The antitumor potential of F-BC-MTX-LPHNPs was further studied.
RESULTS & CONCLUSION: Outcomes suggested that F-BC-MTX-LPHNPs induced the highest apoptosis index (0.89) against MCF-7 cells. Following 30 days of treatment, the residual tumor progression was assessed to be approximately 32%, in animals treated with F-BC-MTX-LPHNPs. F-BC-MTX-LPHNPs are competent to selectively convey the chemotherapeutic agent to the breast cancers. Beta carotene ameliorated MTX-induced hepatic and renal toxicity.
SIGNIFICANCE: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.
METHODS: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.
RESULTS: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.
CONCLUSIONS: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.
Methods: Six different polymers were used to prepare FLU nanopolymeric particles: hydroxyl propyl methylcellulose (HPMC), poly (vinylpyrrolidone) (PVP), poly (vinyl alcohol) (PVA), ethyl cellulose (EC), Eudragit (EUD), and Pluronics®. A low-energy method, nanoprecipitation, was used to prepare the polymeric nanoparticles.
Results and conclusion: The combination of HPMC-PVP and EUD-PVP was found most effective to produce stable FLU nanoparticles, with particle sizes of 250 nm ±2.0 and 280 nm ±4.2 and polydispersity indices of 0.15 nm ±0.01 and 0.25 nm ±0.03, respectively. The molecular modeling studies endorsed the same results, showing highest polymer drug binding free energies for HPMC-PVP-FLU (-35.22 kcal/mol ±0.79) and EUD-PVP-FLU (-25.17 kcal/mol ±1.12). In addition, it was observed that Ethocel® favored a wrapping mechanism around the drug molecules rather than a linear conformation that was witnessed for other individual polymers. The stability studies conducted for 90 days demonstrated that HPMC-PVP-FLU nanoparticles stored at 2°C-8°C and 25°C were more stable. Crystallinity of the processed FLU nanoparticles was confirmed using differential scanning calorimetry, powder X-ray diffraction analysis and TEM. The Fourier transform infrared spectroscopy (FTIR) studies showed that there was no chemical interaction between the drug and chosen polymer system. The HPMC-PVP-FLU nanoparticles also showed enhanced dissolution rate (P<0.05) compared to the unprocessed counterpart. The in vitro antibacterial studies showed that HPMC-PVP-FLU nanoparticles displayed superior effect against gram-positive bacteria compared to the unprocessed FLU and positive control.
METHODS: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages.
RESULTS: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls.
CONCLUSION: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.