查看更多>>摘要：Objective: Statins proved potential bone healing properties. Rosuvastatin is a synthetic, hydrophilic, potent and highly efficacious statin. In the current work, an attempt was investigated to develop, evaluate various bioerodible composite sponges enclosing rosuvastatin and explore their potential in augmenting bone healing and regeneration.Method: Twelve lyophilized sponge formulae were prepared adapting a 4(1).3(1) full factorial design. Xanthan gum, polycarbophil, Carbopol (R) and sodium alginate were investigated as anionic polymers, each at three chitosan:anionic polymer ratios (1:3, 1:1, 3:1). The formula of choice was implanted in fractured rat femora.Results: Visual and microscopic examination showed flexible homogenous porous structures with considerable bending ability. Polyelectrolyte complex formation was proved by DSC and FT-IR for all chitosan/anionic combinations except with xanthan gum where chitosan probably bound to the drug rather than xanthan gum. Statistical analysis proved that anionic polymer type and chitosan: polymer ratio, as well as, their interactions, exhibited significant effects on the release parameters at p0.05. The optimum chitosan/anionic polymer complexation ratios were 3:1 for polycarbophil and 1:1 for Carbopol and alginate. The release at these ratios followed Fiction diffusion while other ratios had anomalous diffusion. Imwitor (R) 900K and HPMC K100M were added as release retarardants for further release optimization. The formula of choice was implanted in fractured rat femora. Histopathological examination revealed advanced stages of healing in treated femora compared to control ones.Conclusion: Biodegradable sponges for local rosuvastatin delivery proved significantly enhanced wound healing and regeneration properties to fractured bones.
查看更多>>摘要：Purpose: For the topical anesthetic, transcriptional transactivator peptide (TAT) modified lidocaine (LID) loaded nanostructured lipid carriers (TAT-NLCs-LID) were prepared and then used for improving transdermal delivery of local anesthetic drug.Methods: In this study, TAT was conjugated with Distearoyl phosphatidylethanolamine-(polyethylene glycol)(2000)-maleimide (DSPE-PEG(2000)-Mal) to obtain TAT-PEG(2000)-DSPE. TAT-NLCs-LID were successfully prepared and characterized by determination of their particle size, morphology, drug encapsulation efficiency and in vitro drug release behavior. The skin permeation of LID-LNPs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro and in vivo anesthesia effect was evaluated on mice.Results: The results showed that TAT-NLCs-LID have substantially small mean diameter (157.9nm) and high encapsulation efficiency (81.8%). From the in vitro skin permeation results, transdermal flux of TAT-NLCs-LID was about several times higher than that of LID solution and NLCs-LID. In vivo anesthesia effect evaluation illustrated that TAT-NLCs-LID can enhance the transdermal delivery of LID by reducing the pain threshold in mice.Conclusion: These results indicate that the novel TAT containing drug delivery system is very useful for overcoming the barrier function of the skin and could deliver anesthetic through the skin. TAT-NLCs-LID could function as promising topical anesthetic system.
查看更多>>摘要：Objective: To overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) in osteosarcoma (OS), biodegradable lipid-coated polymeric nanoparticles (LPNs) were explored for the loading of doxorubicin (DOX) and curcumin (CUR).Methods: DOX plus CUR co-encapsulated LPNs (DOX+CUR LPNs) of mixed lipid monolayer shell and biodegradable polymer core were prepared. The cytotoxicity effect of DOX+CUR LPNs, single drug loaded LPNs, and free drug solutions were evaluated on human OS cell line KHOS cells and mice KHOS cells xenograft in vivo.Results: DOX+CUR LPNs displayed a curative effect on OS cell lines than the free drug counterparts. Also, best anti-OS effects were observed on the animal model compared with other groups tested.Conclusion: This promising dual drugs co-encapsulated lipid-coated polymeric nanoparticulate drug delivery system enhanced the cell delivery and activity of drugs against human OS cancer cell lines and in cancer bearing mice. This research may offer new options for the treatment of OS.
查看更多>>摘要：The current studies entail systematic development of self-nanoemulsifying drug delivery systems (SNEDDS) containing medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) for augmenting the biopharmaceutical performance of artemether. Equilibrium solubility and pseudoternary phase diagram studies facilitated selection of Captex 355 and Ethyl oleate as MCTs and LCTs, and Cremophor RH 40 and Tween 80 as surfactants, while Transcutol HP as cosolvent for formulating the SNEDDS. Systematic optimization was performed employing the Box-Behnken design taking concentrations of lipid, surfactant and cosolvent as the critical material attributes (CMAs), while evaluating for globule size, emulsification time, dissolution efficiency and permeation as the critical quality attributes (CQAs). In situ single pass intestinal perfusion (SPIP) studies in Wistar rats substantiated significant augmentation in the absorption (5- to 6-fold) and permeation (4- to 5-fold) parameters from the optimized MCT and LCT-SNEDDS vis-a-vis the pure drug. In vivo pharmacodynamic studies in Plasmodium berghi infected laca mice exhibited superior reduction in the levels of percent parasitemia, SGOT, SGPT and bilirubin, followed by higher survival rate of the animals by optimized MCT-SNEDDS followed by LCT-SNEDDS vis-a-vis the pure drug, which was subsequently ratified through histopathological examination of liver tissues. Overall, the studies construed successful development of the optimized SNEDDS of artemether with distinctly improved biopharmaceutical and antimalarial potential.
查看更多>>摘要：A series of poly (ester amines) (PEAs) constructed from low molecular weight polyethyleneimine (LPEI, Mw: 0.8k, 1.2k Da) and Pluronic (different molecular weight (Mw) and hydrophilic-lipophilic-balance (HLB)) components were synthesized, and evaluated in vitro and in vivo as gene delivery carriers. Most PEA polymers were able to bind and condense plasmid DNA effectively into particles of approximately 150nm in solution at the polymer/DNA ratio of 5 and above. Transfection efficiency of the PEA polymers depends on particle size of the polymer/DNA complex, molecular weight and HLB of the Pluronics and the size of PEI within PEA composition, as well as the cell type. Significant improvement in gene delivery efficacy was achieved with PEA01/04/05 composed of Pluronic size (Mw: 3000-5000Da), and HLB (12-18) in CHO, C2C12 and HSkM cell lines; and the effective transfection was reflected with PEA 01/04/07 composed of Pluronics with size (2000-5000Da) and HLB (12-23) in mdx mice. The best formulation for pDNA delivery was obtained with PEA 01 producing transgene expression efficiency 5, 19-folds of that of PEI 25k in vitro and in vivo, respectively. These results potent some of these PEA polymers as attractive vehicles for gene or oligonucleotide delivery.
查看更多>>摘要：Recently, microneedle arrays (MAs) have been developed for painless inoculation of vaccines and possess many prominent advantages, including convenience for inoculation, and exact delivery of vaccine to the exact epidermal and dermal or mucosal compartments which teem with antigen-presenting cells (APCs). Among different types of MAs, while the micro-environmental stimulus-responsive MAs represent one of the developmental trends in the field, the MAs combined with the conventional vaccines that are based on nonvirulent viruses, such as live attenuated or whole inactivated viruses, and antigen-encoding DNA viral vectors, have developed rapidly into the advanced stages, with certain products already on clinical trials. The pre- and clinical research outcomes showed that the painless MA delivery of the conventional vaccines through mammalian skin or mucosa can not only elicit robust systemic and even mucosal immunity to pathogens but also, in certain circumstances, redirect the immune response toward a specific Th1 pathway, resulting in cytotoxic T lymphocytes (CTL) to erase the cell-hidden pathogens, thanks to the robust adjuvant function of MAs exerted through damaging the contacted cells to release dangerous signals. This paper focuses on reviewing the latest research and advancements in MA delivery of the conventional vaccines that are based on nonvirulent viruses, underlining MA enhancement of the overall vaccine performance and the most advanced MA vaccine products that are relatively close to markets.
查看更多>>摘要：An effective anti-cancer drug, icariside II (IS), has been used to treat a variety of cancers in vitro. However, its poor aqueous solubility and permeability lead to low oral bioavailability. The aim of this work was to use Solutol (R) HS15 and Pluronic F127 as surfactants to develop novel mixed micelles to enhance the oral bioavailability of IS by improving permeability and inhibiting efflux. The IS-loaded mixed micelles were prepared using the method of ethanol thin-film hydration. The physicochemical properties, dissolution property, oral bioavailability of the male SD rats, permeability and efflux of Caco-2 transport models, and gastrointestinal safety of the mixed micelles were evaluated. The optimized IS-loaded mixed micelles showed that at 4:1 ratio of Solutol (R) HS15 and Pluronic F127, the particle size was 12.88nm with an acceptable polydispersity index of 0.172. Entrapment efficiency (94.6%) and drug loading (9.7%) contributed to the high solubility (11.7mg/mL in water) of IS, which increased about 900-fold. The SF-IS mixed micelle release profile showed a better sustained release property than that of IS. In Caco-2 cell monolayer models, the efflux ratio dramatically decreased by 83.5%, and the relative bioavailability of the mixed micelles (AUC(0-)) compared with that of IS (AUC(0-)) was 317%, indicating potential for clinical application. In addition, a gastrointestinal safety assay also provided reliable clinical evidence for the safe use of this micelle.
Barbosa, Jessica SilvaAlmeida Paz, Filipe A.Braga, Susana Santos
9页
查看更多>>摘要：Montelukast sodium is a leukotriene antagonist of growing interest as an alternative therapy for asthma across different age groups due to its bronchoprotective, anti-inflammatory and anti-allergic properties. Currently, montelukast is commercialized only in oral solid dosage forms, which are the favorite of adult patients but may pose challenges in administration to children of young age or patients suffering from dysphagia. This review presents a comprehensive revision of scientific reports and patents on emerging strategies for the delivery of montelukast. A common ground to these reports is the pursue of an enhanced montelukast performance, by increasing its bioavailability and physico-chemical stability. A wide variety of strategies can be found, from the formation of supramolecular adducts with cyclodextrins to encapsulation in nanoparticles and liposomes. The new dosage forms for montelukast are designed for non-enteric absorption, some for absorption in the oral cavity and another two being for local action in the nasal mucosa or in the pulmonary epithelium. The review describes the emerging delivery strategies to circumvent the current limitations to the use of montelukast that are expected to ultimately lead to the development of more patient-compliant dosage forms.
Tayel, Saadia AhmedEl-Nabarawi, Mohamed AhmedTadros, Mina IbrahimAbd-Elsalam, Wessam Hamdy...
13页
查看更多>>摘要：Context: Pravastatin sodium (PVS) is a freely water-soluble HMG-CoA inhibitor that suffers from instability at gastric pH, extensive first pass metabolism, short elimination half-life (1-3h) and low oral bioavailability (18%). Objective: To overpower these drawbacks and to maximize drug absorption at its main site of absorption at the duodenum, enteric surface-coated PVS-loaded nanocubosomal dispersions were presented. Materials and methods: Glyceryl monooleate (GMO)-based dispersions were developed by the fragmentation or the liquid precursor methods using Pluronic (R) F127 or Cremophor (R) EL as surfactants. As a challenging enteric-coating approach, the promising dispersions were surface-coated via lyophilization with Eudragit (R) L100-55; a duodenum-targeting polymer. The drug content, particle size, zeta potential, morphology and release studies of PVS-loaded dispersions were evaluated before and after surface-coating. Compared to an aqueous PVS solution, the pharmacokinetics of the best achieved system (E-F8) was evaluated (UPLC-MS/MS) in rats. Results: The enteric surface-coated nanocubosomal dispersions were more or less spherical in shape and showed high drug-loading, negative zeta potential values and fine-tuned biphasic drug-release patterns characterized by retarded (2h) and sustained (10h) phases in pH 1.2 and pH 6.8, respectively. E-F8 system showed significantly (p<0.05) higher oral bioavailability, delayed T-max and prolonged MRT0- following oral administration in rats. Conclusions: The duodenum-triggering potential and the controlled-release characteristics of the best achieved system for smart PVS delivery were revealed.
查看更多>>摘要：Biodegradable implants are promising drug delivery systems for sustained release ocular drug delivery with the benefits such as minimum systemic side effects, constant drug concentration at the target site and getting cleared without surgical removal. Dry eye syndrome (DES) is a common disease characterized with the changes in ocular epithelia surface and results in inflammatory reaction that might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is frequently employed for the treatment of DES and it needs to be applied several times a day in tear drops form. The aim of this study was to evaluate in vivo behavior and efficacy of the developed nano-decorated subconjunctival implant systems for sustained release CsA delivery. Biodegradable Poly--caprolactone (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co-glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve sustained release. Two of the formulations PCL-PLGA-NP-F and PCL-PCL-NP-I were selected for in vivo evaluation based on their in vitro characteristics determined in our previous study. In this study, formulations were implanted to Swiss Albino mice with induced dry eye syndrome to investigate the ocular distribution of CsA following subconjunctival implantation and to evaluate the efficacy. Tissue distribution study indicated that CsA was present in ocular tissues such as cornea, sclera and lens even 90 days after the application and blood CsA levels were found lower than ocular tissues. Efficacy studies also showed that application of CsA-loaded fiber implant formulation resulted in faster recovery based on their staining scores.
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Taylor & Francis