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lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system

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Bioactive Materials 2017年第4期2卷 269-280页

作者： Vivek Dave Renu Bala Yadav Kriti Kushwaha Sachdev Yadav Swapnil Sharma Udita Agrawal Department of Pharmacy Banasthali UniversityBanasthaliRajasthanIndia Sagar Institute of Research and Technology-Pharmacy Bhopal462041India

Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceuticalpreparations such as controlled release formulations, parenteral preparations, surgicaltreatment applications, and tissue engineering. In this study, we prepared lipid-polymer hybrid nanoparticlesfor topical and site targeting delivery of Norfloxacin by emulsification solvent evaporationmethod (ESE). The design of experiment (DOE) was done by using software to optimize the result, andthen a surface plot was generated to compare with the practical results. The surface morphology, particlesize, zeta potential and composition of the lipid-polymer hybrid nanoparticles were characterized bySEM, TEM, AFM, and FTIR. The thermal behavior of the lipid-polymer hybrid nanoparticles was characterizedby DSC and TGA. The prepared lipid-polymer hybrid nanoparticles of Norfloxacin exhibited anaverage particle size from 178.6 ± 3.7 nm to 220.8 ± 2.3 nm, and showed very narrow distribution withpolydispersity index ranging from 0.206 ± 0.36 to 0.383 ± 0.66. The surface charge on the lipid-polymerhybrid nanoparticles were confirmed by zeta potential, showed the value from t23.4 ± 1.5 mVto t41.5 ± 3.4 mV. An Antimicrobial study was done against Staphylococcus aureus and Pseudomonasaeruginosa, and the lipid-polymer hybrid nanoparticles showed potential activity against these ***-polymer hybrid nanoparticles of Norfloxacin showed the %cumulative drug release of 89.72% in24 h. A stability study of the optimized formulation showed the suitable condition for the storage oflipid-polymer hybrid nanoparticles was at 4 ± 2 C/60 ± 5% RH. These results illustrated high potential oflipid-polymer hybrid nanoparticles Norfloxacin for usage as a topical antibiotic drug carriers.

关键词： lipid-polymer hybrid nanoparticles Norfloxacin Antimicrobial activity Carbopol gel

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Spatio-temporal delivery of both intra-and extracellular toll-like receptor agonists for enhancing antigen-specific immune responses

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4486-4500页

作者： Nannan Wang Yueyue Zuo Shengjie Wu Chenlu Huang Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

For cancer immunotherapy,triggering toll-like receptors(TLRs)in dendritic cells(DCs)can potentiate antigen-based immune ***,to generate robust and long-lived immune responses,a well-designed nanovaccine should consider different locations of TLRs on DCs and co-deliver both antigens and TLR agonist combinations to synergistically induce optimal antitumor ***,we fabricated lipid-polymer hybrid nanoparticles(LPNPs)to spatio-temporally deliver model antigen ovalbumin(OVA)on the surface of the lipid layer,TLR4 agonist monophosphoryl lipid A(MPLA)within the lipid layer,and TLR7 agonist imiquimod(IMQ)in the polymer core to synergistically activate DCs by both extra-and intra-cellular TLRs for enhancing adaptive immune ***-based nanovaccines exhibited a narrow size distribution at the mean diameter of 133.23 nm and zeta potential of−2.36 mV,showed a high OVA loading(around 70.83μg/mg)and IMQ encapsulation efficiency(88.04%).Our data revealed that LPNPs-based nanovaccines showed great biocompatibility to immune cells and an excellent ability to enhance antigen internalization,thereby promoting DCs maturation and cytokines *** to Free OVA,OVA-LPNPs promoted antigen uptake,lysosome escape,depot effect and migration to secondary lymphatic *** vivo immunization showed that IMQ-MPLA-OVA-LPNPs with dual agonists induced more powerful cellular and humoral immune ***,prophylactic vaccination by IMQ-MPLA-OVA-LPNPs effectively suppressed tumor growth and increased survival ***,the nanovaccines we fabricated can effectively co-deliver antigens and different TLR agonists and realize coordinated stimulation of DCs in a spatio-temporal manner for enhanced immune responses,which provides a promising strategy for cancer immunotherapy.

关键词： lipid-polymer hybrid nanoparticles TLR agonist combinations Ovalbumin Monophosphoryl lipid AImiquimod Nanovaccine Spatio-temporal manner Cancer immunotherapy

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