Improvement of the encapsulation efficiency of oligonucleotide-containing biodegradable microspheres

Freytag, T; Dashevsky, Andrei; Tillman, Lloyd; Hardee, Gregory E.; Bodmeier, Roland

doi:10.1016/s0168-3659(00)00299-6

Cited by 123 publications

(63 citation statements)

References 20 publications

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“…17 However, in the absence of benzyl alcohol, the solvent extraction rate was too rapid for the microspheres to be well formed, and more BSA was entrained into the continuous phase by the higher mass flux of solvent, which was driven by the diffusion from the dispersed phase into the continuous phase. 18 …”

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confidence: 99%

“…19,21,23 An increase in polymer concentration would increase the viscosity of the dispersed phase, leading to bigger droplets and decelerating the diffusion rate of BSA into to the external water phase. 17,23 Therefore, the viscosity of the polymer solution had a significant effect on the size of the microspheres. The solidification of microspheres was faster at higher polymer concentration, which might result in a viscous polymer layer at the microsphere droplet, and it hindered the diffusion of BSA into the external water phase.…”

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confidence: 99%

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Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery

Chen

Zhang

et al. 2014

IJN

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A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 μm to 79.7 μm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery.

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confidence: 99%

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Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery

Chen

Zhang

et al. 2014

IJN

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“…the plasmid loaded plgA-nps (pDnA-PLGA-NPs) were prepared by a modified method of w/o/w double-emulsion process of our lab (20,21). the encapsulating efficiency of PLGA-NPs for pDNA was determined by the ratio of pDnA incorporated in plgA-nps to the total amount of pDnA in formulation (22).…”

Section: Methodsmentioning

confidence: 99%

Efficient inhibition of ovarian cancer by short hairpin RNA targeting claudin-3

Sun

Yi²,

Song³

et al. 2011

Oncol Rep

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Abstract. ovarian cancer is one of the most lethal gynecologic neoplasms. even though various new chemotherapeutics have been developed for the treatment of ovarian cancer, drug resistance and undesired serious side effects remain unavoidable obstacles for chemotherapeutic approaches. new strategies to overcome the therapeutic dilemma are needed. claudin-3 (clDn3) is a recently discovered gene generally overexpressed in human ovarian cancers but not in normal ovarian tissue. Its high expression has been identified to associate with the invasion, proliferation and survival of cancer cells, making it a promising target for gene therapy of ovarian cancer. However, in gene therapy, traditional gene carriers such as virus or cationic liposomes suffer from distressing shortcomings of potential carcinogenicity, obvious cytotoxicity and immunogenicity. nanoparticles (nps) based on plgA are a novel gene delivery system with good biodegradability, excellent biocompatibility and low toxcity for in vivo gene delivery compared with traditional gene carriers. We constructed a plasmid expressing shrnA targeted clDn3 (pshclDn3) encapsulated with plgA-nps, and administered it by i.p. injection to nude mice bearing intraperitoneal sKoV3 ovarian cancer, to investigate the antitumor potential of knocking down clDn3. After 12 times of administration, the tumors of each group were compared. the underlying antitumor mechanisms were revealed by immunostaining of cD31, Ki-67 and tUnel assay, to exhibit possible alterations in microvessel density, cell proliferation and cell apoptosis. our study demonstrated that i.p. administration of pshclDn3 effectively suppressed the expression of clDn3 and, thus, inhibited the growth of ovarian tumors, significantly reducing tumor weight by 67.4% compared with blank controls (p<0.05). Immunostaining of cD31, Ki-67 and tUnel assay demonstrated decreased angiogenesis (p<0.05), reduced proliferation (p<0.05) and increased apoptosis (p<0.05) in the pshclDn3 treated group compared with controls. no obvious toxicity of plgA-nps was observed either in vitro or in vivo. our results indicated that knockdown of clDn3 by pshclDn3 encapsulated in plgA nps may provide a promising approach for the treatment of ovarian cancer. IntroductionOvarian cancer, which accounts for more than 50% death of gynecologic malignancy, is the most lethal gynecologic carcinoma (1). Due to its few and imperceptible early symptoms, ovarian cancer is mostly at advanced stage in most patients during the initial diagnosis. Although patients may initially respond to the combination treatment of surgical and chemical therapies, most of them will inevitably die from relapse and the development of chemotherapy-resistant recurrence (2). The overall 5-year relative survival rate is no more than 50% (3). therefore, new strategies to improve the treatment status of ovarian cancer are urgently needed.gene therapy is a novel therapeutic strategy different from traditional therapies. It exclusively targets the key gene for tumorigenesis, achieves ...

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“…The PLGA (75:25; MW, 50000) nanoparticles with cDNA were prepared by the following modification of a previously described water-in-oilin-water (w/o/w) double emulsion solvent evaporation process (21). Briefly, cDNA was mixed with polylysine (PLL, MW, 25000, Sigma) -5% dextrose in water (5% GS) for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Antitumor effects of PLGA nanoparticles encapsulating the human PNAS-4 gene combined with cisplatin in ovarian cancer

Zhao¹

2011

Oncol Rep

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Abstract. Human PNAS-4 (hPNAS-4), as a pro-apoptotic gene, can inhibit tumor growth when overexpressed in some malignant cells. Poly (lactic-co-glycolic acid) (PLGA) was used as a gene transfer vector due to the advantage of sustained release, nontoxicity and biodegradability. In this study, we aimed to investigate the effect of PLGA nanoparticles encapsulating hPNAS-4 combined with cisplatin (DDP) on ovarian carcinoma. Expression of hPNAS-4 was determined by RT-PCR. Mice bearing intraperitoneal ovarian carcinomas were treated with PBS, pVAX-PLGA nanoparticles (P-P), pVAX-hPNAS-4-PLGA nanoparticles (PhP-P), DDP and PhP-P plus DDP, respectively. Intraperitoneal tumors were weighed to assess the antitumor efficacy. The percentage of proliferative cells and apoptotic cells was evaluated by Ki-67 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The anti-angiogenic effects were detected by CD31 staining and the alginate-encapsulate assay. Overexpression of hPNAS-4 was detected by RT-PCR in the PhP-P and PhP-P plus DDP groups. PhP-P exerted significant antitumor activity through induction of apoptosis, inhibition of cell proliferation and suppression of angiogenesis, compared with treatment with P-P or PBS alone. The combination of PhP-P with DDP showed enhanced antitumor activity compared with therapy of PhP-P or DDP alone. PLGA encapsulating hPNAS-4 combined with DDP may have promising applications in the therapy of ovarian cancer.

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Improvement of the encapsulation efficiency of oligonucleotide-containing biodegradable microspheres

Cited by 123 publications

References 20 publications

Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery

Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery

Efficient inhibition of ovarian cancer by short hairpin RNA targeting claudin-3

Antitumor effects of PLGA nanoparticles encapsulating the human PNAS-4 gene combined with cisplatin in ovarian cancer

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