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Int J Pharm ; 578: 119088, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001291


Docetaxel (DTX), a widely prescribed anticancer agent, is now associated with increased instances of multidrug resistance. Also, being a problematic BCS class IV drug, it poses challenges for the formulators. Henceforth, it was envisioned to synthesize an analogue of DTX with a biocompatible lipid, i.e., palmitic acid. The in-silico studies (molecular docking and simulation) inferred lesser binding of docetaxel palmitate (DTX-PL) with P-gp vis-à-vis DTX and paclitaxel, indicating it to be a poor substrate for P-gp efflux. Solid lipid nanoparticles (SLNs) of the conjugate were prepared using various lipids, viz. palmitic acid, stearic acid, cetyl palmitate and glyceryl monostearate. The characterization studies for the nanocarrier were performed for the surface charge, drug payload, micromeritics, release pattern of drug and surface morphology. From the cytotoxicity assays on resistant MCF-7 cells, it was established that the new analogue offered substantially decreased IC50 to that of DTX. Further, apoptosis assay also corroborated the results obtained in IC50 determination wherein, SA-SLNs showed the highest apoptotic index than free DTX. The conjugate not only enhanced the solubility but also offered lower plasma protein binding and improved pharmacokinetic and pharmacodynamic effect for DTX loaded SA-SLNs in apt animal models, and lower affinity to P-gp efflux. The studies provide preliminary evidence and a ray of hope for a better candidate in its nano version for safer and effective cancer chemotherapy.

Int J Pharm ; 573: 118889, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31765778


The present investigation explores the potential of pH sensitive cationic liposomes for its in vivo tumor targeted gene transfection in comparison to its marketed transfecting reagent Lipofectamine® 2000. The lipoplexes were prepared by varying the molar mass ratio of cationic pH-sensitive liposomes with respect to pDNA and were evaluated for optimum size, zeta potential and for complete gel retardation. Similarly, the stability of lipoplexes in the presence of DNase I and serum was evaluated by using gel retardation and heparin displacement assay. The in vitro hemocompatibility assessment of pDNA lipoplexes revealed < 8.5% of hemolysis which was lower than the hemolysis observed for Lipofectamine® lipoplexes (15.9%). The internalization and pH dependent uptake inhibition using ammonium chloride in MCF-7 cells revealed higher internalization and pH sensitive nature of the prepared pH-sensitive system. The pDNA lipoplexes displayed > 80% of cell viability along with 4.42, 5.18 and 5.00 fold higher transfection efficiency than Lipofectamine® lipoplexes in MCF-7, HeLa and HEK-293 cells respectively. Also the in vivo toxicity assessment exhibited no significant change in the levels of biomarkers and no histopathological deformations in case of pDNA lipoplexes treated animals in comparison to control group (PBS). Further, pDNA lipoplexes demonstrated ~1.3 fold higher tumor transfection over Lipofectamine® lipoplexes indicating superior in vivo gene deliverable capabilities. Thus, the developed pH sensitive lipoplexes promises to be a potential tumor targeting and safe delivery system than Lipofectamine® 2000.

AAPS PharmSciTech ; 20(2): 43, 2019 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-30610392


Among many, the oral route of delivery is considered to be the most favorable route with the highest patient compliance. The main issue with oral delivery is the environmental vulnerability of gastro intestinal tract (G.I.T). The bioavailability could further decrease when drug has poor aqueous solubility and permeability through biological membrane. This drawback could be resolved by employing drug-phospholipid complex strategy, as they utilize mechanism which is similar to the absorption mechanism of nutritional constituents form G.I.T. The drug-phospholipid complexes are considered ideal for oral delivery as they are biodegradable and non-toxic, which enable them to be employed as solubilizer, emulsifier, and as a matrix forming excipient for dugs with poor solubility and/or permeability. The present review compiles the basic know how about the phospholipids and the mechanism through which it improves the bioavailability of drugs. Further, it also compiles the crucial formulation aspects and methods of preparations of drug-phospholipid complex along with its physical and in silico characterization techniques. The increase in number of recent reports involving the utilization of drug-phospholipid complex to improve oral bioavailability of drugs thus explains how vital the strategy is for a successful oral delivery.

Sistemas de Liberação de Medicamentos , Fosfolipídeos/química , Administração Oral , Animais , Disponibilidade Biológica , Humanos , Permeabilidade , Solubilidade
Int J Pharm ; 548(1): 540-558, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-29997043


In recent time, carbon nanotubes (CNTs) have gained vital importance for pharmaceutical formulation scientist for delivering drugs and genes, owing to their excellent surface properties. For example, their aspect ratio is thought to be responsible for their excellent cell penetration aptitude; anisotropic conductivity/semi-conductivity along their axis is ideal for integration with nervous and muscular tissue; an ultrahigh surface area maximizes their ability to "talk" with biological matter; the hollow interior provides an enormous cargo-carrying capacity for drug delivery; and their exteriors are readily functionalized to permit tailoring of solubility and biological recognition. Despite their immense capabilities for the delivery of drugs, genes and other biomedically essential materials, there use is restricted primarily because of the severe toxicity. However, the reactive nature of the surface of the CNTs allowed attaching the guest molecules (drug, siRNA, and diagnostics) of interest which helps in increasing the biocompatibility of these novel nanocarriers. As per the need, CNTs can be modified with peptides, organic molecules, carbohydrates, polymers and used mainly for cancer targeting and tumor cell accumulation. This review expounds different functionalization strategies employed for CNTs that created new opportunities for scientists to improve the potential of delivered therapeutics.

Antineoplásicos , Sistemas de Liberação de Medicamentos , Nanotubos de Carbono , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/toxicidade , Humanos , Nanotubos de Carbono/química , Nanotubos de Carbono/toxicidade , Neoplasias/tratamento farmacológico
Nanomedicine (Lond) ; : 1187-1220, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29905493


Cancer is estimated to be a significant health problem of the 21st century. The situation gets even tougher when it comes to its treatment using chemotherapy employing synthetic anticancer molecules with numerous side effects. Recently, there has been a paradigm shift toward the adoption of herbal drugs for the treatment of cancer. In this context, a suitable delivery system is principally warranted to deliver these herbal biomolecules specifically at the tumorous site. To achieve this goal, carbon nanotubes (CNTs) have been widely explored to deliver anticancer herbal molecules with improved therapeutic efficacy and safety. This review uniquely expounds the biopharmaceutical, clinical and safety aspects of different anticancer herbal drugs delivered through CNTs with a cross-talk on their outcomes. This review will serve as a one-stop-shop for the readers on various anticancer herbal drugs delivered through CNTs as a futuristic delivery device.

Nanoscale ; 10(19): 8911-8937, 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29722421


The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Sistemas de Liberação de Medicamentos , Nanotubos de Carbono , Pele/efeitos dos fármacos , Liberação Controlada de Fármacos , Humanos , Interferência de RNA , Absorção Cutânea