Abstract:For many applications, polymer microspheres (MS) should possess a monodisperse size distribution. With such uniformity they are able to deliver precise amounts of drug per MS, optimize the release kinetics of an encapsulated drug, obtain repeatable in vivo biodistributions to different organs and tissues, and obtain the maximum protection of (protein) drugs from degradation. This review classifies monodisperse polymer MS according to their methods of production and gives examples of the formation of uniform MS… Show more
“…The polydispersity index (PDI), a measure of the distribution of diameters was maintained at values less than 0.14 for up to 14 days. These PDI values are within the recommended size for medical applications, which is a PDI of less than0.3 26 . Thezeta potential (the overall surface charge of the particles) also did not significantly change during this time.…”
P21 activated kinases-1 (PAK-1)is implicated in various diseases. It is inhibited by thesmall molecule ‘Inhibitor targeting PAK1 activation-3’ (IPA-3), which is highly specific but metabolically unstable. To address this limitation we encapsulatedIPA-3 in sterically stabilized liposomes (SSL). SSL-IPA-3 averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of −28.1, neither of which changed over 14 days; however, the PDI increased to 0.139. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after 7 days. SSL-IPA-3 inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Excitingly, only a 2 day/week dose of SSL-IPA-3 was needed to inhibit the growth of prostate xenografts in vivo, while a similar dose of free IPA-3 was ineffective. These data demonstrate the development and clinical utility of a novel liposomal formulationfor the treatment of prostate cancer.
The small molecule ‘Inhibitor targeting P21-activated kinase-1 (PAK1) activation-3’ (IPA-3) has potential anti-cancer effects, but is metabolically unstable. We encapsulated IPA-3 in sterically stabilized liposomes (SSL) that averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of −28.1, which was stable for over 14 days with 70 % of IPA-3 remaining even after 7 days. A 2 day/week administration of 5 mg/Kg dose of SSL-IPA-3 significantly inhibited the growth of prostate xenografts in vivo as compared to similar dose of free IPA-3, demonstrating the potential benefits of SSL-IPA-3 for the management of prostate cancer.
“…The polydispersity index (PDI), a measure of the distribution of diameters was maintained at values less than 0.14 for up to 14 days. These PDI values are within the recommended size for medical applications, which is a PDI of less than0.3 26 . Thezeta potential (the overall surface charge of the particles) also did not significantly change during this time.…”
P21 activated kinases-1 (PAK-1)is implicated in various diseases. It is inhibited by thesmall molecule ‘Inhibitor targeting PAK1 activation-3’ (IPA-3), which is highly specific but metabolically unstable. To address this limitation we encapsulatedIPA-3 in sterically stabilized liposomes (SSL). SSL-IPA-3 averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of −28.1, neither of which changed over 14 days; however, the PDI increased to 0.139. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after 7 days. SSL-IPA-3 inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Excitingly, only a 2 day/week dose of SSL-IPA-3 was needed to inhibit the growth of prostate xenografts in vivo, while a similar dose of free IPA-3 was ineffective. These data demonstrate the development and clinical utility of a novel liposomal formulationfor the treatment of prostate cancer.
The small molecule ‘Inhibitor targeting P21-activated kinase-1 (PAK1) activation-3’ (IPA-3) has potential anti-cancer effects, but is metabolically unstable. We encapsulated IPA-3 in sterically stabilized liposomes (SSL) that averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of −28.1, which was stable for over 14 days with 70 % of IPA-3 remaining even after 7 days. A 2 day/week administration of 5 mg/Kg dose of SSL-IPA-3 significantly inhibited the growth of prostate xenografts in vivo as compared to similar dose of free IPA-3, demonstrating the potential benefits of SSL-IPA-3 for the management of prostate cancer.
“…Polydispersity index (PDI) of Lp, Lp/pcDNA and ILp/pcDNA was 0.105, 0.215 and 0.125, respectively. All values were within the recommended size for medical applications, which is a PDI of less than 0.3 [ 21 ]. Fig.…”
BackgroundAnti-CD105 mAb-conjugated immunoliposomes, loaded with secreted mouse endostatin gene, were developed for targeted tumor imaging and antiangiogenic gene therapy.MethodsThe liposomes were investigated for size, zeta-potential, lipid content, antibody binding ability, and pcDNA loading capacity. The ability of immunoliposomes to target tumor-derived endothelial cells and perform gene transfer in vitro was measured and their basic biocompatibility was evaluated. A nude mouse/breast cancer xenograft model was used to examine the tumor internalization of fluorescent-labeled liposomes and the clinical potential of immnuoliposomes loaded with pcDNA3.1-CSF1-endostatin. ResultsLoaded immunoliposomes were homogenously distributed with a well-defined spherical shape and bilayer, diameter of 122 ± 11 nm, and zeta potential + 1.40 mV. No significant differences were observed in body weight, liver index, oxidative stress, or liver and kidney function in mice after liposomes exposure. The addition of CD105 mAb to liposomes conferred the ability to target tumor-derived endothelial cells in vitro and in vivo. Systemic intravenous administration of fluorescent immunoliposomes in the xenograft model resulted in selective and efficient internalization in tumor vasculature. Treatment of mice with pcDNA3.1-CSF1-endostatin-loaded immunoliposomes suppressed tumor growth by 71%.ConclusionsThese data demonstrate the advantages of using anti-CD105 mAb-conjugated immunoliposomes to enhance tumor targeting, imaging, and gene transfer applications.
“…2f), as assessed by flow cytometry, followed a unimodal distribution. The coefficient of variation (CV) of microgel size was 6.5%, falling within a quasi-monodisperse distribution 20 . Microgel size and dispersity were found to be unaffected by the pre-coating procedure (Fig.…”
Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel’s mechanical properties1. Here, we report a microfluidic-based method for encapsulating single cells in a ~6 micron layer of alginate that increases the proportion of cell-containing microgels by 10-fold, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly-encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.
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