Synthesis of biocompatible poly(ɛ-caprolactone)- block-poly(propylene adipate) copolymers appropriate for drug nanoencapsulation in the form of core-shell nanoparticles

Figures & data

Figure 1 Schematic presentation of the chemical reactions during the preparation of poly(propylene adipate)-block-poly(ɛ-caprolactone) copolymers.

Abbreviation: PPAd, poly(propylene adipate).

Table 1 Theoretical and calculated compositions, intrinsic viscosities, and molecular weights of prepared polymers

Sample	%wt	%mol	%mol ^1H NMR	%mol ^13C NMR*	[η] (dL/g)	Average Mn (g/mol)	Average Mw (g/mol)	Mw/Mn
PCL	0/100	0/100	0/100	0/100	0.53	15,300	47,700	3.12
PPAd/PCL 10/90	10/90	6.37/93.63	6.12/93.88	6.74/93.26	0.42	19,300	50,500	2.61
PPAd/PCL 20/80	20/80	13.28/86.72	12.97/87.03	13.36/86.64	0.53	12,300	32,800	2.67
PPAd/PCL 30/70	30/70	20.80/79.20	23.31/76.69	21.27/78.73	0.40	13,200	34,300	2.60
PPAd/PCL 55/45	55/45	42.82/57.18	43.13/56.87	44.15/55.85	0.41	16,900	36,100	2.13
PPAd/PCL 65/35	65/35	53.24/46.76	55.45/44.55	55.33/44.67	0.42	19,400	38,600	1.99
PPAd/PCL 85/15	85/15	77.62/22.38	77.07/22.93	79.98/20.02	0.43	11,000	24,900	2.26
PPAd	100/0	100/0	100/0	100/0	0.57	13,700	28,900	2.10

* Note: Estimated from diol carbons a from polycaprolactone, bonded to the ester oxygen.

Abbreviations: ¹H NMR, hydrogen-1 nuclear magnetic resonance; ¹³C NMR, carbon-13 nuclear magnetic resonance; %mol, percentage concentration; %wt, weight percent; M_n, number average molecular weight; M_w, weight average molecular weight; PCL, poly(ɛ-caprolactone); PPAd, poly(propylene adipate).

Figure 2 Hydrogen-1 nuclear magnetic resonance (¹H NMR) spectra of poly–(ɛ-caprolactone) (PCL), poly(propylene adipate) (PPAd), and PPAd/PCL 85/15 weight/weight copolymer (A) and ¹H NMR spectra of PPAd/PCL 85/15 weight/weight copolymer at the region 3.98–4.16 ppm (B).

Figure 3 Carbon-13 nuclear magnetic resonance (¹³C NMR) spectrum of poly(ɛ-caprolactone) (PCL), poly(propylene adipate) (PPAd), and their copolymer PPAd/PCL 65/35 weight/weight (A) and ¹³C-NMR spectrum at region 173 ppm of PPAd/PCL 65/35 weight/weight (B).

Table 2 Composition, probabilities of triads, randomness factor, and the average number sequence lengths of synthesized copolyesters

Sample	Normalized peak areas of carbonyl carbons (%)				Triad sequence probabilities (%)			Composition PPAd/PCL ^13C NMR*	β	LnPPAd	LnPCL
	CL-CL	CL-Ad	Ad-CL	Ad-Ad	P(CL-CL-CL)	P(CL-Ad-CL)	P(Ad-Ad-Ad)
PPAd/PCL 10/90	92.43	1.58	0.85	5.14	92.43	2.42	5.14	6.35/93.65	0.20	5.24	77.27
PPAd/PCL 20/80	84.93	2.89	1.12	11.07	84.93	4.01	11.07	13.07/86.93	0.18	6.52	43.38
PPAd/PCL 30/70	75.27	2.75	2.92	19.05	75.27	5.67	19.05	21.89/78.11	0.17	7.72	27.53
PPAd/PCL 55/45	55.38	1.72	4.78	38.12	55.38	6.50	38.12	41.37/58.63	0.13	12.74	18.05
PPAd/PCL 65/35	42.68	6.08	0.56	50.67	42.68	6.65	50.67	53.99/46.01	0.13	16.24	13.84
PPAd/PCL 85/15	20.01	2.08	2.13	75.78	20.01	4.21	75.78	77.89/22.12	0.12	37.00	10.51

* Note: Estimated from the split carbonyl carbons.

Abbreviations: ¹³C NMR, carbon-13 nuclear magnetic resonance; β, randomness factor; Ad-Ad, carbonyl carbon of PPAd; Ad-CL, carbonyl carbon of PPAd bonded to carbonyl carbon of PCL; CL-Ad, carbonyl carbon of PCL bonded to carbonyl carbon of PPAd; CL-CL, carbonyl carbon of PCL; LnPPAd, length of PPAd; LnPCL, length of PCL; PCL, poly(ɛ-caprolactone); PPAd, poly(propylene adipate).

Table 3 Glass transition temperature, melting temperature, heat of fusion values, and degree of crystallinity of poly(ɛ-caprolactone), poly(propylene adipate), and their copolymers

Sample	Tg (°C)	Tm1 (°C)	Tm2 (°C)	ΔHm (J/g)	Xc (%)*
PCL	−68.2	54.8	58.1	68.66	55.1
PPAd/PCL 10/90	−67.8	51.0	55.7	66.73	46.2
PPAd/PCL 20/80	−65.9	49.2	53.9	57.41	42.4
PPAd/PCL 30/70	−64.4	40.0	48.7	56.98	37.7
PPAd/PCL 55/45	−64.8	32.0	43.3	47.65	24.5
PPAd/PCL 65/35	−64.3	21.9	36.1	44.93	12.4
PPAd/PCL 85/15	−62.5	−2.9	12.8	7.09	8.5
PPAd	−56.1	31.1	41.8	35.93	26.8

* Note: Calculated from wide angle X-ray diffraction patterns.

Abbreviations: ΔH_m, heat of fusion, PCL, poly(ɛ-caprolactone); PPAd, poly (propylene adipate); T_g, glass transition temperature; T_m, melting temperature; X_c, degree of crystallinity. ^{10 20 30}

Figure 4 X-ray diffraction patterns for synthesized polyesters.

Abbreviations: PCL, poly(ɛ-caprolactone); PPAd, poly(propylene adipate).

Figure 5 Differential scanning calorimetric thermograms of neat polymers and synthesized copolymers.

Abbreviations: PCL, poly(ɛ-caprolactone); PPAd, poly(propylene adipate).

Figure 6 Viability of human umbilical vein endothelial cells as a function of copolymer type and concentration (cell incubation time: 24 hours).

Abbreviations: PCL, poly(ɛ-caprolactone); PPAd, poly(propylene adipate).

Table 4 Characteristics of prepared desferrioxamine-loaded nanoparticles such as average diameter, polydispersity index, zeta potential, nanoparticles yield (%), drug loading (%), and entrapment efficiency (%)

Sample	Mean particle size (nm)	Polydispersity index	Zeta potential (mV)	Nanoparticles yield (%)	Drug loading (%)	Entrapment efficiency (%)
PCL	177 ± 3.22	0.148 ± 0.034	−32.55 ± 1.89	15.61 ± 2.19	0.857 ± 0.118	1.458 ± 0092
PPAd/PCL 10/90	171 ± 2.25	0.106 ± 0.017	−37.82 ± 0.97	18.71 ± 0.81	1.096 ± 0.059	2.630 ± 0.139
PPAd/PCL 20/80	176 ± 2.82	0.134 ± 0.009	−31.76 ± 0.79	16.08 ± 2.66	1.008 ± 0.073	1.735 ± 0.062
PPAd/PCL 30/70	185 ± 1.35	0.129 ± 0.012	−31.90 ± 1.09	20.82 ± 2.65	1.024 ± 0.163	2.474 ± 0.198
PPAd/PCL 55/45	194 ± 0.897	0.165 ± 0.019	−28.75 ± 1.89	21.27 ± 3.72	1.180 ± 0.048	2.537 ±0.130
PPAd/PCL 65/35	242 ± 2.88	0.341 ± 0.021	−34.22 ± 0.30	17.04 ± 2.18	1.030 ± 0.166	1.977 ± 0.006
PPAd/PCL 85/15	232 ± 3.46	0.194 ± 0.024	−28.21 ± 2.60	19.55 ± 2.78	0.641 ± 0.072	1.467 ± 0.106
PPAd	241 ± 2.35	0.362 ± 0.021	−34.60 ± 2.02	26.53 ± 3.16	1.058 ± 0.108	1.852 ± 0.069

Abbreviations: PCL, poly(ɛ-caprolactone); PPAd, poly(propylene adipate).

Figure 7 Scanning electron microscope photos from desferrioxamine-loaded poly(ɛ-caprolactone) (A) and poly(propylene adipate)/poly(ɛ-caprolactone) 65/35 weight/weight (B) nanoparticles.

Abbreviation: SEI, secondary electron imaging.

Figure 8 High-resolution transmission electron microscope photos from prepared nanoparticles poly(propylene adipate)/poly(ɛ-caprolactone) 30/70 weight/weight.

Figure 9 X-ray diffraction patterns of desferrioxamine mesylate and drug-loaded nanoparticles.

Abbreviations: PCL, poly(ɛ-caprolactone); PPAd, poly(propylene adipate).

Figure 10 (A) Dissolution profiles of desferrioxamine from prepared nanoparticles. The release rate in copolymer containing 85 weight percent poly(propylene adipate) (PPAd) was not possible to study due to the softness of the material. (B) Illustration of possible distribution patterns of drug in the self-assembly PPAd/poly(ɛ-caprolactone) (PCL) nanoparticles based high-resolution transmission electron microscope micrographs and its possible influence on early drug release from the nanoparticles.

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