Novel pentablock copolymer (PLA–PCL–PEG–PCL–PLA)-based nanoparticles for controlled drug delivery: effect of copolymer compositions on the crystallinity of copolymers and in vitro drug release profile from nanoparticles

Abstract

The purpose of this investigation was to design novel pentablock copolymers (polylatide-polycaprolactone-polyethylene glycol- polycaprolactone-polylatide) (PLA-PCL-PEG-PCL-PLA) to prepare nanoparticle formulations which provide continuous delivery of steroids over a longer duration with minimal burst effect. Another purpose was to evaluate the effect of poly (L-lactide) (PLLA) or poly (D, L-lactide) (PDLLA) incorporation on crystallinity of pentablock copolymers and in vitro release profile of triamcinolone acetonide (selected as model drug) from nanoparticles. PLA-PCL-PEG-PCL-PLA copolymers with different block ratio of PCL/PLA segment were synthesized. Release of triamcinolone acetonide from nanoparticles was significantly affected by crystallinity of the copolymers. Burst release of triamcinolone acetonide from nanoparticles was significantly minimized with incorporation of proper ratio of PDLLA in the existing triblock (PCL-PEG-PCL) copolymer. Moreover, pentablock copolymer based nanoparticles exhibited continuous release of triamcinolone acetonide. Pentablock copolymer based nanoparticles can be utilized to achieve continuous near zero-order delivery of corticosteroids from nanoparticles without any burst effect.

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

“…Suspending the MPs in gel creates a depot where particles remains localized during release. The hydrogel also provides an additional diffusion barrier to peptide released from MPs and thus may extend duration of release (Patel et al, 2014d; Tamboli et al, 2013). …”

“…Among various approaches investigated for sustained delivery of biologics, nano- and micro-particles (e.g., Sandostatin LAR® depot containing octreotide) have been effective and clinically approved for various ailments (Patel et al, 2014b; Vaishya et al, 2014). Octreotide is a semisynthetic cyclic octapeptide and a somatostatin analog indicated for the treatment of acromegaly (De Martino et al, 2010).…”

“…MPs are formulated with PLGA-glucose polymer for delivery over a period of 4 weeks. Lactide- and glycolide-based biodegradable polymers such as poly(D,L-lactide-coglycolide) (PLGA) and poly(D,L-lactide) (PLA) are FDA-approved and have been widely investigated for the sustained release of therapeutic peptides and proteins (Vaishya et al, 2014; Vaishya and Mitra, 2014). However, these polymers may not be suitable for delivering peptide and protein biologics as recent studies indicate that peptides/proteins are susceptible to acylation within the microenvironment of particles during release (Ghassemi et al, 2012; Ibrahim et al, 2005; Murty et al, 2003).…”

Synthesis of mid-chain functional macrophotoinitiators of poly(D,L-lactide) homopolymer and tetrablock poly(D,L-lactide)-poly(ε-caprolactone) copolymer by ring-opening polymerization

“…More recently, novel pentablock copolymer (PLA-PCL-PEG-PCL-PLA)-based nanoparticles for controlled drug delivery and multiblock thermoplastic elastomers based on PCL derivative and PLA have been synthesized and characterized. [14,21] Here, we describe the controlled synthesis of well-defined mid-chain macrophotoinitiators of PDLLA polymer by ROP and PCL-PDLLA tetrablock copolymer by sequential ROP using Sn(Oct) 2 /alcohol as the initiating systems.…”

Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy

“…However, it is well known that PCL is extremely hydrophobic and its degradation is too slow to meet the needs for drug delivery. [19][20][21] Moreover, the PCL NPs could be rapidly removed in the liver and captured by the reticuloendothelial system (RES) when they are injected into the blood stream. 22 A large number of approaches for prolonging the circulation of NPs in blood have been reported.…”