Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers

Wang, Lulu; Ma, Yingying; Gu, Yu; Liu, Yangyang; Zhao, Juan; Yan, Beibei; Wang, Yancai

doi:10.1080/02652048.2018.1462416

Cited by 46 publications

(20 citation statements)

References 25 publications

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“…Such increase in particle size during lyophilization might be contributed by thermodynamic tendency of particles to aggregate during freeze drying even though osmotic activity of mannitol counteracts to a great extent. The results of present study are consistent with earlier published results 32 . Eventually, the optimized formulation lyophilized using mannitol (10% w/v) as cryoprotectant was selected for further studies.…”

Section: Resultssupporting

confidence: 94%

Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential

Sharma

Mehta

2019

Sci Rep

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Atorvastatin, a favored option for hyperlipidemia exhibits the problem of poor gastric solubility and low absolute bioavailability (12%) along with higher pre-systemic clearance (>80%). Therefore, to circumvent these limitations, atorvastatin nanocrystals were prepared using poloxamer-188 as stabilizer via high pressure homogenization technique followed by lyophilization. Various variables like drug to poloxamer-188 ratio, homogenization cycle, homogenization pressure, type and concentration of cryoprotectant were optimized to achieve uniform nanosized crystals with good dispersibility. Solid state characterization by ATR-FTIR and DSC revealed no incompatible physicochemical interaction between drug and excipients in formulation while DSC and PXRD collectively corroborated the reduced crystallinity of drug in nanocrystals. Size analysis and SEM confirmed nanometric size range of nanocrystals (225.43 ± 24.36 nm). Substantial improvement in gastric solubility (~40 folds) and dissolution rate of drug in nanocrystals was observed. Pharmacokinetic study in wistar rats revealed significant improvement in oral bioavailability (~2.66 folds) with atorvastatin nanocrystals compared to pure drug. Furthermore, reduction in serum total lipid cholesterol, LDL and triglyceride content justified the effectiveness of formulation at 50% less dose of atorvastatin along with improved plasma safety profile in comparison of pure drug. In conclusion, atorvastatin nanocrystals are safe and efficacious drug delivery system confirming potent competence in treatment of hyperlipidemic conditions with ease of scalability for commercialization.

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Section: Resultssupporting

confidence: 94%

Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential

Sharma

Mehta

2019

Sci Rep

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“…Freeze-drying of liposomes resulted in the increment in particle size, reaching up to 500 nm (Figure 4). Various food compatible cryoprotectants such as sucrose, mannitol and lactose can be used to address this issue [77]. Thus, food compatible sucrose was tested as a cryoprotectant [56].…”

Section: Resultsmentioning

confidence: 99%

Development and Characterization of Liposomal Formulations Containing Phytosterols Extracted from Canola Oil Deodorizer Distillate along with Tocopherols as Food Additives

et al. 2019

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Phytosterols are plant sterols recommended as adjuvant therapy for hypercholesterolemia and tocopherols are well-established anti-oxidants. However, thermo-sensitivity, lipophilicity and formulation-dependent efficacy bring challenges in the development of functional foods, enriched with phytosterols and tocopherols. To address this, we developed liposomes containing brassicasterol, campesterol and β-sitosterol obtained from canola oil deodorizer distillate, along with alpha, gamma and delta tocopherol. Three approaches; thin film hydration-homogenization, thin film hydration-ultrasonication and Mozafari method were used for formulation. Validated liquid chromatographic tandem mass spectrometry (LC-MS/MS) was utilized to determine the entrapment efficiency of bioactives. Stability studies of liposomal formulations were conducted before and after pasteurization using high temperature short time (HTST) technique for a month. Vesicle size after homogenization and ultrasonication (<200 nm) was significantly lower than by Mozafari method (>200 nm). However, zeta potential (−9 to −14 mV) was comparable which was adequate for colloidal stability. Entrapment efficiencies were greater than 89% for all the phytosterols and tocopherols formulated by all three methods. Liposomes with optimum particle size and zeta potential were incorporated in model orange juice, showing adequate stability after pasteurization (72 °C for 15 s) for a month. Liposomes containing phytosterols obtained from canola waste along with tocopherols were developed and successfully applied as a food additive using model orange juice.

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“…The physicochemical evaluation was done for particle size, surface zeta potential and polydispersity index (PDI) using Zetasizer Nano ZS 90 (Malvern Instruments, UK). Thereafter, nanoplex were lyophilized for stability concern using 3%w/v trehalose 50 . Further DEPC treated nuclease-free PBS (1×) was added to the nanoplex for making the final dose and was utilized for administration.…”

Section: Methodsmentioning

confidence: 99%

Method and its Composition for encapsulation, stabilization, and delivery of siRNA in Anionic polymeric nanoplex: An In vitro- In vivo Assessment

Raval

Jogi

Gondaliya

et al. 2019

Sci Rep

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Small interfering RNA (siRNA) are synthetic RNA duplex designed to specifically knockdown the abnormal gene to treat a disease at cellular and molecular levels. In spite of their high potency, specificity, and therapeutic potential, the full-fledged utility of siRNA is predominantly limited to in vitro set-up. Till date, Onpattro is the only USFDA approved siRNA therapeutics available in the clinic. The lack of a reliable in vivo siRNA delivery carrier remains a foremost obstacle towards the clinical translation of siRNA therapeutics. To address the obstacles associated with siRNA delivery, we tested a dendrimer-templated polymeric approach involving a USFDA approved carrier (albumin) for in vitro as well as in vivo delivery of siRNA. The developed approach is simple in application, enhances the serum stability, avoids in vivo RNase-degradation and mediates cytosolic delivery of siRNA following the endosomal escape process. The successful in vitro and in vivo delivery of siRNA, as well as targeted gene knockdown potential, was demonstrated by HDAC4 inhibition in vitro diabetic nephropathy (DN) podocyte model as well as in vivo DN C57BL/6 mice model. The developed approach has been tested using HDAC4 siRNA as a model therapeutics, while the application can also be extended to other gene therapeutics including micro RNA (miRNA), plasmids oligonucleotides, etc.

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Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers

Cited by 46 publications

References 25 publications

Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential

Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential

Development and Characterization of Liposomal Formulations Containing Phytosterols Extracted from Canola Oil Deodorizer Distillate along with Tocopherols as Food Additives

Method and its Composition for encapsulation, stabilization, and delivery of siRNA in Anionic polymeric nanoplex: An In vitro- In vivo Assessment

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