Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery

Patel, Sulabh; Vaishya, Ravi; Pal, Dhananjay; Mitra, Ashim K.

doi:10.1208/s12249-014-0196-6

Cited by 29 publications

(25 citation statements)

References 35 publications

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“…6 and 7. Our laboratory specializes in particle-in-gel formulations (Khurana et al, 2014; Mishra et al, 2011; Mitra and Mishra, 2011; Patel et al, 2014c; Patel et al, 2015; Patel et al, 2014d). Pentablock thermoresponsive polymer (PLA 250 -PCL 1250 -PEG 1500 -PCL 1250 -PLA 250 ) was utilized to sustain the release of octreotide.…”

Section: Resultsmentioning

confidence: 99%

Reversible hydrophobic ion-paring complex strategy to minimize acylation of octreotide during long-term delivery from PLGA microparticles

Vaishya

Mandal

Gokulgandhi

et al. 2015

International Journal of Pharmaceutics

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Acylation of peptide has been reported for a number of peptides and proteins during release from polymers comprising of lactide and glycolide. We hypothesize that reversible hydrophobic ion-pairing (HIP) complex may minimize octreotide acylation during release. Sodium dodecyl sulfate (SDS), dextran sulfate A (DSA, Mw 9–20kDa) and dextran sulfate B (DSB, Mw 36–50kDa) were selected as ion-pairing agents to prepare reversible HIP complex with octreotide. Complexation efficiency was optimized with respect to the mole ratio of ion-pairing agent to octreotide to achieve 100% complexation of octreotide. Dissociation studies suggested that DSA-octreotide and DSB-octreotide complexes dissociate completely at physiological pH in presence of counter ions unlike SDS-octreotide complex. DSA-octreotide and DSB-octreotide complex encapsulated PLGA microparticles (DSAMPs and DSBMPs) were prepared using the S/O/W emulsion method. Entrapment efficiencies for DSAMPs and DSBMPs were 74.7±8.4% and 81.7±6.3%, respectively. In vitro release of octreotide was performed by suspending MPs in gel. A large fraction of peptide was released in chemically intact form and <7% was acylated from DSAMPs and DSBMPs in gel over 55 days. Therefore, HIP complexation could be a viable strategy to minimize acylation of peptides and proteins during extended release from lactide and glycolide based polymers.

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Section: Resultsmentioning

confidence: 99%

Reversible hydrophobic ion-paring complex strategy to minimize acylation of octreotide during long-term delivery from PLGA microparticles

Vaishya

Mandal

Gokulgandhi

et al. 2015

International Journal of Pharmaceutics

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“…Patel et al, developed novel biodegradable pentablock copolymer based nanoparticle system for sustained release of proteins. Various pentablock copolymers were utilized to encapsulate biologics such as IgG, bevacizumab and FITC-BSA [25,91]. Pentablock copolymers examined in several ocular cell lines, did not demonstrate any cytotoxicity or inflammatory mediator release with in vitro studies.…”

Section: Novel Colloidal Delivery Systemsmentioning

confidence: 99%

“…Pentablock copolymers examined in several ocular cell lines, did not demonstrate any cytotoxicity or inflammatory mediator release with in vitro studies. [25,92]. Moreover, Ig-G, bevacizumab and FITC-BSA were released over prolonged period of time.…”

Section: Novel Colloidal Delivery Systemsmentioning

confidence: 99%

“…Moreover, Ig-G, bevacizumab and FITC-BSA were released over prolonged period of time. In addition, released Ig-G was stable as native Ig-G for prolonged time [25,91]. Therefore, such formulations may be applied to anti-VEGF therapies in order to be delivered to the back-of-the-eye tissues for treatment of posterior diseases.…”

Section: Novel Colloidal Delivery Systemsmentioning

confidence: 99%

“…Therefore, novel drug delivery strategies that will minimize or eradicate concerns associated with frequent intraocular injections are pivotal. Elevation of IOP is not the only side effect caused by frequent intravitreal injections, possibility of retinal detachment, retinal hemorrhage, and endophthalmitis have been reported [25]. …”

Section: Introductionmentioning

confidence: 99%

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Recent perspectives on the delivery of biologics to back of the eye

Joseph

Trinh

Cholkar

et al. 2016

Expert Opinion on Drug Delivery

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Introduction Biologics are generally macromolecules, large in size with poor stability in biological environments. Delivery of biologics to tissues at the back of the eye remains a challenge. To overcome these challenges and treat posterior ocular diseases, several novel approaches have been developed. Nanotechnology-based delivery systems, like drug encapsulation technology, macromolecule implants and gene delivery are under investigation. We provide an overview of emerging technologies for biologics delivery to back of the eye tissues. Moreover, new biologic drugs currently in clinical trials for ocular neovascular diseases have been discussed. Areas Covered Anatomy of the eye, posterior segment disease and diagnosis, barriers to biologic delivery, ocular pharmacokinetic, novel biologic delivery system Expert Opinion Anti-VEGF therapy represents a significant advance in developing biologics for the treatment of ocular neovascular diseases. Various strategies for biologic delivery to posterior ocular tissues are under development with some in early or late stages of clinical trials. Despite significant progress in the delivery of biologics, there is unmet need to develop sustained delivery of biologics with nearly zero-order release kinetics to the back of the eye tissues. In addition, elevated intraocular pressure associated with frequent intravitreal injections of macromolecules is another concern that needs to be addressed.

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