Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Drug Deliv Transl Res ; 12(11): 2824-2837, 2022 11.
Article in English | MEDLINE | ID: mdl-35678961

ABSTRACT

Orally delivered molecularly targeted small-molecule drugs play a significant role in managing cancer as a chronic disease. However, due to the poor oral bioavailability of some of these molecules, high-dose administration is required leading to dose-limiting toxicity especially when delivered daily for a long duration. Here, we report an oral nanoformulation for small-molecule multi-kinase inhibitor, sorafenib tosylate, showing nearly two fold enhancement in the oral bioavailability and enhanced therapeutic efficacy with a better safety profile compared to the current clinical formulation. Using a scalable process involving high-pressure homogenization, sorafenib was loaded into an albumin nanocarrier at ~ 50 w/w%. Repeated preparation of gram-scale batches (n = 7) showed an average particle size of 180 ± 9 nm, encapsulation efficiency of 95 [Formula: see text] 2%, and drug-loading efficiency of 48 [Formula: see text] 0.7%. Further, surface engineering with a mucoadhesive layer on nanoparticles (referred to as ABSORF) resulted in the final size of 299 ± 38 nm and surface charge of -54 ± 8 mV. Single-dose and multidose pharmacokinetic studies showed two fold enhancement in the plasma concentration of sorafenib compared to current clinically used tablets. Antitumor efficacy studies in the orthotopic rat liver tumor model showed significant tumor regression (p value = 0.0037) even at half dose (eqv. to 200 mg of human equivalent dose) of ABSORF compared to clinical control (eqv. to 400 mg). The biodistribution of sorafenib from ABSORF was higher in the liver; however, liver and kidney function test parameters were comparable with that of the 2 × dose of clinical control. No abnormalities and signs of toxicity were seen in the histopathological analysis for ABSORF-treated animals. In summary, we demonstrate a scalable preparation of small-molecule drug-loaded nanoformulation with approximately two fold enhancement in oral bioavailability, improved antitumor efficacy, and acceptable toxicity profile.


Subject(s)
Nanoparticles , Administration, Oral , Albumins , Animals , Biological Availability , Drug Carriers , Humans , Particle Size , Rats , Sorafenib , Tissue Distribution
2.
Tissue Eng Regen Med ; 17(2): 123-140, 2020 04.
Article in English | MEDLINE | ID: mdl-31953618

ABSTRACT

BACKGROUND: Human adipose tissue is a great source of translatable biomaterials owing to its ease of availability and simple processing. Reusing discardable adipose tissue for tissue regeneration helps in mimicking the exact native microenvironment of tissue. Over the past 10 years, extraction, processing, tuning and fabrication of adipose tissue have grabbed the attention owing to their native therapeutic and regenerative potential. The present work gives the overview of next generation biomaterials derived from human adipose tissue and their development with clinical relevance. METHODS: Around 300 articles have been reviewed to widen the knowledge on the isolation, characterization techniques and medical applications of human adipose tissue and its derivatives from bench to bedside. The prospective applications of adipose tissue derivatives like autologous fat graft, stromal vascular fraction, stem cells, preadipocyte, adipokines and extracellular matrix, their behavioural mechanism, rational property of providing native bioenvironment, circumventing their translational abilities, recent advances in featuring them clinically have been reviewed extensively to reveal the dormant side of human adipose tissue. RESULTS: Basic understanding about the molecular and structural aspect of human adipose tissue is necessary to employ it constructively. This review has nailed the productive usage of human adipose tissue, in a stepwise manner from exploring the methods of extracting derivatives, concerns during processing and its formulations to turning them into functional biomaterials. Their performance as functional biomaterials for skin regeneration, wound healing, soft tissue defects, stem cell and other regenerative therapies under in vitro and in vivo conditions emphasizes the translational efficiency of adipose tissue derivatives. CONCLUSION: In the recent years, research interest has inclination towards constructive tissue engineering and regenerative therapies. Unravelling the maximum utilization of human adipose tissue derivatives paves a way for improving existing tissue regeneration and cellular based therapies and other biomedical applications.


Subject(s)
Adipose Tissue , Biocompatible Materials , Tissue Engineering/methods , Adipocytes , Cell Differentiation , Cell- and Tissue-Based Therapy , Extracellular Matrix , Humans , Prospective Studies , Stem Cells , Tissue Scaffolds , Wound Healing
3.
Curr Drug Deliv ; 14(5): 641-649, 2017.
Article in English | MEDLINE | ID: mdl-27758693

ABSTRACT

BACKGROUND: Flutamide (FLT) is a non steroidal antiandrogenic drug used to treat prostate cancer. Its poor aqueous solubility and toxicity are the major hindrance for oral drug delivery. The aims of this study are to introduce nanoformulation of flutamide to increase its aqueous solubility thereby improves the therapeutic efficacy of the chemodrug. METHODS: Poly (vinyl alcohol) (PVA) coated flutamide nanoparticles (PVA FLT NPs) were formulated by nanoprecipitation method and characterized by DLS, TEM, FTIR, Drug release profile and biological assays. RESULTS: The PVA FLT nanoparticles were about 300nm size and spherical in shape. The PVA coated flutamide nanoparticles were monodispersed and polycrystalline. The FTIR spectra confirmed the encapsulation of flutamide in PVA FLT NPs. The encapsulation efficiency and loading efficiency was found to be about 78% and 15% respectively. The in vitro drug release of nanoparticles was calculated and it showed a sustained release up to 120 hrs at pH 7.4. The in vitro cytotoxicity, colony forming ability and blood compatibility were also investigated. The in vitro cytotoxicity study indicated the dose dependent cytotoxicity of PVA FLT NPs. In vitro clonogenic assay revealed that the PVA FLT NPs treated PC3 cells had less colony forming ability than the untreated PC3 cells. In vitro hemolysis assay and blood aggregation studies confirmed the hemocompatibility of the prepared PVA FLT NPs. CONCLUSION: We reported PVA coated FLT NPs were prepared by nanoprecipitation were more aqueous soluble than FLT, which increased its therapeutic efficacy for prostate cancer cells.


Subject(s)
Drug Carriers , Flutamide/pharmacology , Nanoparticles , Prostatic Neoplasms/pathology , Alcohols , Cell Line, Tumor , Drug Liberation , Humans , Male , Particle Size , Prostatic Neoplasms/drug therapy
4.
J Funct Biomater ; 6(3): 849-62, 2015 Aug 25.
Article in English | MEDLINE | ID: mdl-26308065

ABSTRACT

Injectable hydrogels are gaining popularity as tissue engineering constructs because of their ease of handling and minimal invasive delivery. Making hydrogels from natural polymers helps to overcome biocompatibility issues. Here, we have developed an Amorphous Chitin (ACh)-Agarose (Agr) composite hydrogel using a simpletechnique. Rheological studies, such as viscoelastic behavior (elastic modulus, viscous modulus, yield stress, and consistency), inversion test, and injectability test, were carried out for different ACh-Agr concentrations. The composite gel, having a concentration of 1.5% ACh and 0.25% Agr, showed good elastic modulus (17.3 kPa), yield stress (3.8 kPa), no flow under gravity, injectability, and temperature stability within the physiological range. Based on these studies, the optimum concentration for injectability was found to be 1.5% ACh and 0.25% Agr. This optimized concentration was used for further studies and characterized using FT-IR and SEM. FT-IR studies confirmed the presence of ACh and Agr in the composite gel. SEM results showed that the lyophilized composite gel had good porosity and mesh like networks. The cytocompatibility of the composite gel was studied using human mesenchymal stem cells (hMSCs). The composite gels showed good cell viability.These results indicated that this injectable composite gel can be used for biomedical applications.

SELECTION OF CITATIONS
SEARCH DETAIL
...