Biomedical subjects

Mansoor M Amiji

Publications and source records attributed to Mansoor M Amiji.

12 recordsLinked to original sources

PubMed2006

Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for HIV/AIDS.

PURPOSE: This study aims at developing poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticulate system as an intracellular delivery vehicle for saquinavir, an anti-HIV protease inhibitor. MATERIALS AND METHODS: Saquinavir-loaded PEO-PCL nanoparticles were prepared by a solvent displacement process. The formed nanoparticles were characterized for size, surface charge, and surface presence of PEO chains. Cellular uptake and distribution of the nanoparticle was examined in THP-1 human monocyte/macrophage (Mo/Mac) cell line. Intracellular saquinavir concentrations were measured as a function of dose and duration of incubation. RESULTS: The PEO-PCL nanoparticles had a smooth surface and spherical shape and showed a relatively uniform size distribution with a mean particle diameter of approximately 200 nm. The surface presence of PEO chains was confirmed by an increase in the -C-O-(ether) signature of the C1s spectra in electron spectroscopy for chemical analysis. Rapid cellular uptake of rhodamine-123 encapsulated PEO-PCL nanoparticles was observed in THP-1 cells. Intracellular saquinavir concentrations when administered in the nanoparticle formulation were significantly higher than from aqueous solution. CONCLUSIONS: This study shows that PEO-PCL nanoparticles provide a versatile platform for encapsulation of saquinavir and subsequent intracellular delivery in Mo/Mac cells.

Anti-HIV Agents↗

PubMed2006

Multi-functional polymeric nanoparticles for tumour-targeted drug delivery.

The use of nanoparticles as drug delivery vehicles for anticancer therapeutics has great potential to revolutionise the future of cancer therapy. As tumour architecture causes nanoparticles to preferentially accumulate at the tumour site, their use as drug delivery vectors results in the localisation of a greater amount of the drug load at the tumour site; thus improving cancer therapy and reducing the harmful nonspecific side effects of chemotherapeutics. In addition, formulation of these nanoparticles with imaging contrast agents provides a very efficient system for cancer diagnostics. Given the exhaustive possibilities available to polymeric nanoparticle chemistry, research has quickly been directed at multi-functional nanoparticles, combining tumour targeting, tumour therapy and tumour imaging in an all-in-one system, providing a useful multi-modal approach in the battle against cancer. This review will discuss the properties of nanoparticles that allow for such multiple functionality, as well as recent scientific advances in the area of multi-functional nanoparticles for cancer therapeutics.

Animals↗

PubMed2006

Nanoparticulate drug carriers for delivery of HIV/AIDS therapy to viral reservoir sites.

Providing the optimum treatment of AIDS is a major challenge in the 21st Century. HIV is localised and harboured in certain inaccessible compartments of the body, such as the CNS, the cerebrospinal fluid, the lymphatic system and in the macrophages, where it cannot be reached by the majority of therapeutic agents in adequate concentrations or in which the therapeutic agents cannot reside for the necessary duration. Progression in HIV/AIDS treatment suggests that available therapy can lower the systemic viral load below the detection limit. However, on discontinuation of treatment, there is relapse of the infection from the reservoir sites and a potential for resistance development. This review discusses the aetiology and pathology of HIV, with emphasis on the viral reservoirs, current therapy of AIDS, and the opportunity for nanotechnology-based drug delivery systems to facilitate complete eradication of viral load from the reservoir sites. Literature-cited examples of drug delivery systems that are under investigation for the treatment of AIDS are discussed. The article also focuses on the future outlook and strategies for investigational drug formulations that use nanotherapeutic strategy for HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2006

A review of nanocarrier-based CNS delivery systems.

Drug delivery to the central nervous system (CNS) is one of the most challenging fields of research and development for pharmaceutical and biotechnology products. A number of hydrophilic therapeutic agents, such as antibiotics, anticancer agents, or newly developed neuropeptides do not cross the blood brain barrier (BBB) after systemic administration. The BBB is formed by the tight junctions at the brain capillary endothelial cells, which strictly control drug transfer from blood to brain. Drug modification, osmotic opening of cerebral capillary endothelium, and alternative routes for administration (e.g., intracerebral delivery) have been successfully used to enhance drug transport to the CNS. The use of nanocarriers, such as liposomes and solid polymeric or lipid nanoparticles may be advantageous over the current strategies. These nanocarriers can not only mask the BBB limiting characteristics of the therapeutic drug molecule, but may also protect the drug from chemical/enzymatic degradation, and additionally provide the opportunity for sustained release characteristics. Reduction of toxicity to peripheral organs can also be achieved with these nanocarriers. This review article discusses the various barriers for drug delivery to the CNS and reviews the current state of nanocarriers for enhancing drug transport into the CNS.

Animals↗

PubMed2005

Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design.

The tremendous progress witnessed in the field of biotechnology with respect to discovery of therapeutic and antigenic proteins has propelled the need for development of suitable oral delivery devices for these and other macromolecules. In this study, we report the encapsulation of fluorescein isothiocyanate (FITC)-labeled gelatin nanoparticles into poly(epsilon-caprolactone) (PCL) microsphere (nanoparticle-in-microsphere oral delivery system, NiMOS) by double emulsion like technique and the influence of variables such as polymer concentration in organic phase, amount of nanoparticles added as internal phase, and the speed of homogenization on particle size of NiMOS using a 3(3) randomized full factorial design. A statistical model with interaction terms was derived to predict the particle size of the hybrid system. The results from multiple linear regression analysis and Student's t-test revealed that for obtaining large particles of NiMOS, a high polymer concentration and low speed of homogenization was necessary. In contrast, to obtain particles of smaller size, high speed of homogenization was found to be very important. The mathematical model obtained was validated for prediction of particle size. The encapsulation of gelatin nanoparticles in PCL microsphere was confirmed by fluorescent microscopy. Based on the statistical model we were also successful in producing NiMOS of less than 10 mum in size, which could be used as oral delivery system for therapeutic and antigenic macromolecules.

Administration, Oral↗

PubMed2005

Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer.

This study was carried out to evaluate and compare the biodistribution profile of tamoxifen when administered intravenously (i.v.) as a simple solution or when encapsulated in polymeric nanoparticulate formulations, with or without surface-stabilizing agents. Tamoxifen-loaded, poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were prepared by solvent displacement process that allowed in situ surface modification via physical adsorption of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock polymeric stabilizer (Pluronic). The nanoparticles were characterized for particle size and surface charge. Presence of PEO chains on nanoparticle surface was ascertained by electron spectroscopy for chemical analysis (ESCA). In vivo biodistribution studies were carried out in Nu/Nu athymic mice bearing a human breast carcinoma xenograft, MDA-MB-231 using tritiated [(3)H]-tamoxifen as radio-marker for quantification. PEO-PCL nanoparticles with an average diameter of 150-250 nm, having a smooth spherical shape, and a positive surface charge were obtained with the formulation procedure. About 90% drug encapsulation efficiency was achieved when tamoxifen was loaded at 10% by weight of the polymer. Aqueous wettability, suspendability, and ESCA results showed surface hydrophilization of the PCL nanoparticles by the Pluronics. The primary site of accumulation for the drug-loaded nanoparticles after i.v. administration was the liver, though up to 26% of the total activity could be recovered in tumor at 6h post-injection for PEO-modified nanoparticles. PEO-PCL nanoparticles exhibited significantly increased level of accumulation of the drug within tumor with time as well as extended their presence in the systemic circulation than the controls (unmodified nanoparticles or the solution form). Pluronic surfactants (F-68 and F-108) presented simple means for efficient surface modification and stabilization of PCL nanoparticles to achieve preferential tumor-targeting and a circulating drug reservoir for tamoxifen.

Animals↗

PubMed2005

Long-circulating polymeric nanovectors for tumor-selective gene delivery.

Significant advances in the understanding of the genetic abnormalities that lead to the development, progression, and metastasis of neoplastic diseases has raised the promise of gene therapy as an approach to medical intervention. Most of the clinical protocols that have been approved in the United States for gene therapy have used the viral vectors because of the high efficiency of gene transfer. Conventional means of gene delivery using viral vectors, however, has undesirable side effects such as insertion of mutational viral gene into the host genome and development of replication competent viruses. Among non-viral gene delivery methods, polymeric nanoparticles are increasingly becoming popular as vectors of choice. The major limitation of these nanoparticles is poor transfection efficiency at the target site after systemic administration due to uptake by the cells of reticuloendothelial system (RES). In order to reduce the uptake by the cells of the RES and improve blood circulation time, these nanoparticles are coated with hydrophilic polymers such as poly(ethylene glycol) (PEG). This article reviews the use of such hydrophilic polymers employed for improving the circulation time of the nanocarriers. The mechanism of polymer coating and factors affecting the circulation time of these nanocarriers will be discussed. In addition to the long circulating property, modifications to improve the target specificity of the particles and the limitations of steric protection will be analyzed.

Animals↗

PubMed2003

Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery.

The main objective of this study was to develop and characterize a pH-sensitive biodegradable polymeric nanoparticulate system for tumor-selective paclitaxel delivery. A representative hydrophobic poly(beta-amino ester) (poly-1) was synthesized by conjugate addition of 4,4'-trimethyldipiperidine with 1,4-butanediol diacrylate. Poly-1 (M(n) 10,000 daltons) nanoparticles were prepared by the controlled solvent displacement method in an ethanol-water system in the presence of Pluronic) F-108, a poly(ethylene oxide) (PEO)-containing non-ionic surfactant. Control and PEO-modified nanoparticles were characterized by Coulter counter, scanning electron microscopy (SEM), zeta potential measurements, and electron spectroscopy for chemical analysis (ESCA). Polymer degradation studies were performed in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. Paclitaxel loading capacities and efficiencies were determined and release studies were performed in Tween)-80 (0.1%, w/v)-containing PBS at 37 degrees C. Control and PEO-modified nanoparticles, labeled with rhodamine-123, were incubated with BT-20 cells to examine the uptake and cellular distribution as a function of time. PEO-modified nanoparticles with an average size of 100-150 nm and a positive surface charge of 37.0 mV were prepared. SEM analysis showed distinct smooth, spherical particles. The ether (-C-O-) peak of the C(1s) envelope in ESCA confirmed the surface presence of PEO chains. Polymer biodegradation studies showed that almost 85% of the starting material degraded after 6 days. The maximum paclitaxel loading efficiency attained was 97% at 1.0% (w/w) of the drug. Paclitaxel release studies showed that approximately 10% was released in the first 24 h, 80% after 3 days, and the entire content was released in approximately 5 days. After 1 h of incubation, a large fraction of the administered control and PEO-modified poly-1 nanoparticles was internalized in BT-20 cells. Results of this study demonstrate that PEO-modified poly-1 nanoparticles could provide increased therapeutic benefit by delivering the encapsulated drug to solid tumors.

Drug Delivery Systems↗

PubMed2003

Cellular uptake and concentrations of tamoxifen upon administration in poly(epsilon-caprolactone) nanoparticles.

PURPOSE: In an attempt to increase the local concentration of tamoxifen in estrogen receptor positive breast cancer cells, we have prepared and characterized poly(epsilon-caprolactone) (PCL) nanoparticle formulation. METHODS: PCL (mol wt 14,800 daltons) nanoparticles were prepared by the solvent displacement method in acetone-water system in the presence of Pluronic F- 68. PCL nanoparticles, labeled with rhodamine123, were incubated with MCF-7 estrogen receptor positive breast cancer cells to determine uptake, intracellular distribution, and localization as a function of time. Intracellular drug concentrations over a specified period of time using different initial doses were examined using tritiated [3H]-tamoxifen. RESULTS: A significant fraction of the administered rhodamine123-loaded PCL nanoparticles was found in the perinuclear region of the MCF-7 cells, where estrogen receptors are also localized, after 1 hour of incubation. Measurements of the intracellular concentrations revealed that most of the administered nanoparticle dose was internalized within the first 30 minutes of incubation, and the uptake followed saturable transport kinetics. CONCLUSION: Results of this study show that PCL nanoparticles were rapidly internalized in MCF-7 cells and intracellular tamoxifen concentrations followed a saturable process. This approach may provide better therapeutic benefit by delivering the drug locally, near the tumor cells, for a longer period of time.

Administration, Oral↗

PubMed2002

Biodegradable poly(epsilon -caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen.

To increase the local concentration of tamoxifen in estrogen receptor (ER) positive breast cancer, we have developed and characterized nanoparticle formulation using poly(epsilon -caprolactone) (PCL). The nanoparticles were prepared by solvent displacement method using acetone-water system. Particle size analysis, scanning electron microscopy, zeta potential measurements, and differential scanning calorimetry (DSC) were used for nanoparticle characterization. Biodegradation studies were performed in the presence and absence of Pseudomonas lipase in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. Tamoxifen loading over different concentrations was analyzed by high-performance liquid chromatography (HPLC) and the optimum loading concentration was determined. In vitro release studies were performed in 0.5% (w/v) sodium lauryl sulfate (SLS) containing PBS at 37 degrees C. Cellular uptake and distribution of fluorescent-labeled nanoparticles was examined in MCF-7 breast cancer cells. SEM micrographs and Coulter analysis showed nanoparticles with spherical shape and uniform size distribution (250-300 nm), respectively. Zeta potential analysis revealed a positive surface charge of +25 mV on the tamoxifen-loaded formulation. Being hydrophobic crystalline polyester, PCL did not degrade in PBS alone, but the degradation was enhanced by the presence of lipase. The maximum tamoxifen loading efficiency was 64%. Initial burst release of tamoxifen was observed, probably due to significant surface presence of the drug on the nanoparticles. A large fraction of the administered nanoparticle dose was taken up by MCF-7 cells through non-specific endocytosis. The nanoparticles were found in the perinuclear region after 1 h. Results of the study suggest that nanoparticle formulations of selective ER modulators, like tamoxifen, would provide increased therapeutic benefit by delivering the drug in the vicinity of the ER.

Absorbable Implants↗

PubMed2002

Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation.

In order to examine the efficacy of paclitaxel (Taxol, Bristol-Myers Squibb) after administration locally at the tumor site, we have developed a thermo-reversible gelling formulation in poloxamer 407 (Pluronic F-127) solution. Paclitaxel was incorporated in poloxamer 407 [20% (w/w)] at 0.5- and 1.0-mg/mL concentrations. The in vitro release studies were carried out in phosphate-buffered saline (pH 7.4) at 37 degrees C. Control and paclitaxel-poloxamer 407 formulations were administered intratumorally at a dose of 20 mg/kg in B16F1 melanoma-bearing mice. The change in tumor volume as a function of time and the survival of treated animals were used as measures of efficacy. Poloxamer 407 solution undergoes a reversible sol-gel transition when the temperature is raised to above 21 degrees C. In vitro paclitaxel release from poloxamer 407 gels was very slow (only 6.1% after 6 hr) probably due to the poor aqueous solubility of the drug. Significant enhancement in the anti-tumor efficacy was noted following intratumoral administration of paclitaxel-poloxamer 407 formulation. The initial tumor growth rate was delayed by 67% and the tumor volume doubling time was increased by 72% relative to saline control. In addition, more than 91% of the tumor-bearing animals that received paclitaxel in poloxamer 407 gel survived on day 15 post-administration as compared to 58% in the control group. The results of this study show significant benefit of paclitaxel for solid tumor when administered locally in an in situ gelling poloxamer 407 formulation.

Animals↗

PubMedDate not supplied

Improved oral delivery of paclitaxel following administration in nanoemulsion formulations.

Nanoemulsion formulations were designed for enhancing the oral bioavailability of hydrophobic drugs. Paclitaxel was selected as a model hydrophobic drug, which is also a substrate for the P-glycoprotein efflux system. The oil-in-water (o/w) nanoemulsions were formulated with pine nut oil as the internal oil phase, egg lecithin as the primary emulsifier, and water as the external phase. Stearylamine and deoxycholic acid were used to impart positive and negative charge to the emulsions, respectively. Nanoemulsions were prepared by sonication method and characterized for particle size and surface charge. The control and nanoemulsion formulations with tritiated [3H]-paclitaxel were administered orally to female C57BL/6 mice and the distribution of the drug was examined. The formulated nanoemulsions had a particle size range of approximately 90-120 nm (laser diffraction method) and zeta potential values ranging from -56 mV to +34 mV. Following oral administration, a significantly higher concentration of paclitaxel was observed in the systemic circulation when administered in the nanoemulsion relative to control aqueous solution. The absorbed drug was found to be distributed in the liver, kidneys, and lungs. The results of this study suggest that nanoemulsions are promising novel formulations that can enhance the oral bioavailability of hydrophobic drugs, like paclitaxel.

Administration, Oral↗