pha(eng)
DESCRIPTION
My research at the Laboratory of Polymers, University of CataniaTRANSCRIPT
UNIVERSITA ’ DEGLI STUDI DI CATANIAFACOLTA ’ DI FARMACIA
PhD in Medicinal Chemistry
GIUSEPPE PUZZO
BACTERIAL FERMENTATION AND MICROWAVE-ASSISTED SYNTHESIS FOR THE PRODUCTION OF
BIODEGRADABLE AND BIOCOMPATIBLE POLYMERS USABLE IN THE PHARMACEUTICAL
FIELD.
Tutor:Prof. Alberto Ballistreri.
Ciclo XXIV
Coordinator:Prof. Giuseppe Ronsisvalle.
Introduction
Not biodegradable plastics
Biodegradable plastics
Biodegradable polymers on the market.
Mater-Bi®Ecoflex®Biomax®
EcoPLA® PHA
Polyhydroxyalkanoates (PHA)
PHASCL: short-chain length PHA3-5 carbon atoms
PHAMCL: medium -chain length PHA6-14 carbon atoms
Poly(3-hydroxyalkanoates) with R= alkyl or functional group
n
Physical and chemical properties.
Polymer Tg(°C) Tm (°C) Cristallinity (%) Extension at break (%)
P(3HB) 15 175 50-80 5
P(3HB-co-3HV) -1 145 56 50
P(3HB-co-4HB) -7 150 43 444
PP -15 176 50 400
•Average molecular weight ranging between 5·104 and1·106 Da
•Enantiomerically pure
•Biodegradable and biocompatible
Applications of PHAs in medicine and pharmaceutical s.
•Sutures. •Bone graft substitutes.
•Temporary heart valves. •Carrier for drug delivery.
Role of PHAs in tissue engineering .
The aim of the thesis
Explore new strategies for obtaining new polymers which, in the pharmaceutical field, have feature of biodegradability and biocompatibility with wider opportunity of utilization with respect to poly(3-hydroxybutyrate) (PHB) by:
1. The study on the capabilty to P. aeruginosa to grow and synthesize PHAs from Long Chain Fatty Acids (LCFA) or vegetable oils, with better yields or with new structures and new properties.
2. Chemical synthesis of new coplymers and terpolymers bytransesterification reaction microwave assisted.
PHA’s production by microorganisms.
Corn, sugar cane, potato etc
Substrates for PHA ’s production.
Glucose
Alkanoates(propionic acid,
butyric acid, valeric acid etc.)
Fatty acid
Carbohydrate
Vegetable oils and fats
Agriculture, waste materials
Table 1. PHA production from P. aeruginosa culturedusing odd carbon atoms fatty acids as carbon source.
Fatty acid Dry cell weight(mg/L)
PHA content(% dry cell weight)
PHA yield(mg/L)
Eptadecanoic -N 1600 9,8 157
Nonadecanoic -N 2370 5,3 127
2 737 0,25 7Eneicosanoic-N
GC trace of the products prepared by methanolysis ofPHA from nonadecanoic acid.
V= 3-hydoxyvalerate; H= 3-hydoxyheptanoate; O= 3-hydroxy octanoate; N= 3-hydroxynonanoate; D= 3-hydroxydecanoate; U= 3-hydrox yundecanoate; Θ= 3-hydroxytridecanoate; P = 3-hydroxypentadecanoate
200 MHz 1H-NMR spectra of the PHAs obtained from P. aeruginosa grown on (a) heptadecanoic; (b) nonadecanoic and (c) eneicosanoic acid.
50 MHz 13C-NMR spectra of the PHAs obtained from P. aeuruginosa grown on (a) nonanoic; (b) heptadecanoic and (c) eneicosanoic acid .
Chemical structure of the PHAs .
l m n o p
V H N U∆
Θ
4
5
6
8
9
10
12
13
7
11
4
5
6
8
9
10
7
11
4
5
6
8
9
7
4
5
6
7
4
5
123 123 123 123 123
O CH CH2CO
CH2
CH3
O CH CH2CO O CH CH
2CO O CH CH
2CO O CH CH
2CO
CH2
CH2
CH2
CH3
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH
CH
CH2
CH2
CH2
CH2
CH2
CH2
CH3
q
P
4
5
6
8
9
10
12
13
7
11
123
O CH CH2CO
CH2
CH
CH
CH2
CH2
CH2
CH2
CH2
CH2
CH2
14
15
CH2
CH3
Fatty acids Tg (°C) Tm (°C) ∆∆∆∆Hm (J/g) Mw x 10 -3 Mw/Mn
Eptadecanoic -41 50 7,9 77 1,6
Nonadecanoic -43 58 12 97 2
49 5,7 188 1,7
Table 2. Physical characteristics of the PHAs isolated from P. aeruginosa grown on C-odd fatty acids.
Eneicosanoic -39
Thermal degradation of PHAs
A measure of the fit of the calculated oligomers intensiti es tothe experimental ones is given by the agreement factor (AF); the lower AF, the closer fit.
Assuming a Bernoullian (random ) distribution of repeating unitsin these copolymers, the probability of finding a given Ax , By…Nz can be calculated by the Leibnitz formula as follows :
∑∑∑∑
∑∑∑∑ ++++====
ii
iicalci
I
IIAF 2
.exp
2..exp )(
Negative ion ESI mass spectrum of the partial pyrolisate of the PHA fromenicosanoic acid. R may be an un n-etyl, n-butyl, n-hex yl, n-octyl, n-decyl and n-dodecyl group.
R CH CH CO CH
R
O CH2 CO O CH
R
CH2 COOH[ ]n
m/z ESI CalculatedDimers
V-H 227 4 4V-N; H2 255 15 15
V-U; H-N 383 18 18V-Θ; H-U; N2 311 26 26
V-P; N-U; H-Θ 339 20 20H-P; U2; N-Θ 367 12 13
U-Θ; N-P 395 5 5
TrimersC23 411 8 9C25 439 14 16C27 467 23 22C29 495 21 24C31 523 15 18C33 551 10 10C35 579 3 0
Table 3. Experimental and calculated relative amounts ofthe partial pyrolisis products of P. aeruginosa fromeneicosanoic acid.
Brassica carinataproduction’s seeds
Formulation
Remaining
flourDe-oiling
Soil products
As such
Fertilizer products
As such
Lubricants
Agricoltural
oils
Modified
LubrificantsEnergy
Oil
Biofuels
Table 4. PHA production from P. aeruginosa cultured on differents substrates.
Substrate Dry cell weight(mg/L)
PHA content(% dry cell weight)
PHA yield(mg/L)
B. Carinata oil 1000 5,0 50
Oleico acid 380 15,0 57
2 866 9,3 81Erucic acid
416 10.0Nervonic acid 10416 42
Table 5. Comonomer composition (mol% ) of PHA obtainedfrom varius carbon sources, determined by GC.
C= 3-hydroxyhexanoate; O= 3-hydroxyoctanoate; O :1= 3-hydroxy-5-octenoate; D= 3-hydroxydecanoate; D :1= 3-hydroxy-7-decenoate; Δ= 3-hydroxydodecanoate; Δ:1= 3-hydroxy-6-dodecenoate; T :1 = 3- hydroxy-5-tetradecenoate; T :2= 3-hydroxy-5,8-tetradecadienoate; T :3= 3-hydroxy-5,8,11-tetradecatrienoate.
Substrate C O O:1 D D:1Δ Δ:1 T:1 T:2 T:3
B.Carinata oil 3 34 3 32 3 10 1 9 2 3
Oleico acid 4 55 - 27 - 8 - 6 - -
Erucico acid 3 43 - 36 - 10 - 8 - -
Nervonico acid 4 28 - 43 - 14 - 11 - -
200 MHz 1H-NMR spectra of the PHA obtained from erucic acid.
C6, O8, D10,
∆12, T:1 14
T:1
6
C5, O5-7, D5-9,
∆5-11, T:1 8-13
C/O/D/∆/T:1
3
T:1
4
T:1
7
C/O/D/∆/T:1
2
C/O/D/∆
4
T:1
5
(ppm)1.01.52.02.53.03.54.04.55.05.5
50 MHz 13C-NMR spectra of the PHA obtained from erucic acid.
170 120130(ppm)
70 152025303540
C/O/D/∆
1
T:1
1 T:1
6
T:1
5
O/D/∆
3
T:1
3
C3
C4
T:1
2
C/O/D/∆
2
O6 T:1
4
O/D/∆
4
D8
∆10
T:1
12
D6-7
∆6-9
T:1
8-11
T:1
7
D9
∆11
T:1
13
C5
O5D5
D5
O7
D10
∆12
T:1
14
C6
O8
m n o p q
C O D ∆
∆
T:1
4
5
6
8
9
10
12
13
14
7
11
4
5
6
8
9
10
12
7
11
4
5
6
8
9
10
7
4
5
6
8
7
4
5
6
123 123 123 123 123
O CH CH2CO
CH2
CH2
O CH CH2CO O CH CH
2CO O CH CH
2CO O CH CH
2CO
CH3
CH2
CH2
CH2
CH2
CH3
CH2
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH
CH
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
Chemical structure of the PHAs from oleic, erucic and nervonic acids.
200 MHz 1H-NMR spectra of the PHA obtained from B. carinata oil.
(ppm)1.01.52.02.53.03.54.04.55.05.5
O:1 6
T:2/T:3 6
O:1 5
D:1 7-8
∆:1 6-7
T:2 5, 8-9
T:3 5, 8-9, 11-12
O:1/D:1/∆:1/T:2/T:
3
3
T:2 7
T:3 7, 10
O:1/T:2/T:3
4
O:1 7
D:1 6, 9
∆:1 5, 8
T:2 10
T:3 13O:1/D:1/∆:1/T:2/T:3
2
D:1
∆:1
4
O:1 8, D:1 10, ∆:112, T:2/T:3 14
D:1 5, ∆:1 9-11, T:2 11-13
50 MHz 13C-NMR spectra of the PHA obtained from B. carinata oil.
170 120130(ppm)
70 152025303540
D:1
∆:1
1 O:1
T:2
T:3
1
D:1
∆:1
3
O:1
T:2
T:3
3
O:1
T:2
T:3
2
D:1
∆:1
2
D:1
∆:1
4
O:1
T:2
T:3
4 ∆:1
9
∆:1
12
T:2
14O:1
8
D:1
10
T:3
14
T:2 7
T:3 7, 10
O:1 7, D:1 6/9, ∆:1 5, 8 T:2 10, T:3 13}
(ppm)120122124126128130132134136138
O:1
6
T:1
6
T:3
12
D:1
8
O:1
5
T:1
5
T:3
5
T:2
5
D:1
7
∆:1
6
T:3
8, 11
T:3
9
T:2
8T:2
6
T:2
9∆:1
7
T:3
6
13C-NMR spectra of the PHA obtained from B. carinata oil in the regionof the olefinc signals.
n o p r s
O:1 D:1 ∆:1 T:2 T:3
4
5
6
8
9
10
12
13
14
7
11
4
5
6
8
9
10
12
7
11
4
5
6
8
9
10
7
4
5
6
8
7
4
5
6
123 123 123 123 123
O CH CH2CO
CH2CH
O CH CH2CO O CH CH
2CO O CH CH
2CO O CH CH
2CO
CH
CH2CH
2CH
2CH
CH
CH2CH
2CH
CH
CH2
CH2
CH2
CH2CH
CH
CH2
CH
CH
CH2
CH2
CH2
CH2CH
CH
CH2
CH
CH
CH2
CH
CH
CH2
CH3
7CH2
8CH3
9CH2
10CH3
11CH2
12CH3
13CH2
14CH3
Chemical structure of the PHA from B. carinata oil. This PHA is made up of all the repeating units constituting the PHA from erucic acid, plus the unsatureted ones shown here.
Sustrate Tg (°C) Tm (°C) ΔHm (J/g) Mw x 10 -3 Mw/Mn
B.carinata oil -47 - - 56 1,8
Oleico acid -52 - - 57 2,2
Erucic acid -46 50 16,1 122 1,9
Nervonic acid -43 50 15,5 114 2
Table 6. Physical characteristics of the PHAs isolated fromP. aeruginosa grown on B. carinata oil and on oleic, erucicand nervonics acids.
700
(m/z)
20
60
100Pentameri
EsameriEptameri
x 3
700 800 900 1000 1100
765737 907793 935879
709 8211049
1077851 963 1021 1105 1133991 1161
(m/z)300 400 500 600
20
60
100
Dimeri
TrimeriTetrameri
255 425 623595393 651535 567 679
339
311283
367453 481
509% In
tens
ità%
Inte
nsità
R CH CH CO CH
R
O CH2 CO O CH
R
CH2 COOH[ ]n
Negative ion ESI mass spectrum of the partial pyrolisate of the PHA from erucic acid. R may be a n-propyl, n-pentyl, n-heptyl, n- nonyl or n-undecenyl group.
m/z ESI CalculatedDimers
C-O 255 10 9C-D; O2 283 24 24
C-Δ; O-D 311 26 26O-Δ; D2 339 18 19
O-T:1 365 6 7D-Δ 367 8 7D-T:1 393 6 4Δ-T:1 421 2 2
TrimersC22 397 4 4C24 425 12 12C26 453 20 19C28 481 18 20
C30 :1 507 5 7C30 509 13 13
C32:1 535 10 9C32 537 6 5
C34:1 563 8 6
Table 7. Experimental and calculated relative amounts ofthe partial pyrolisis products of the PHA produced by P. aeruginosa from erucic acid.
Negative ion ESI mass spetrum of the partial pyrolisate of the PHA from B. carinata. R may be a n-pentaenyl, n-heptaenyl, n-nonaenye, n-undecadieyil or n-undecatrienyl group.
300 400 500 600 700(m/z)
20
60
100
651509
255
283 339
311
367393
425453 481
535 567 595 623679
Dimeri
Trimeri
Tetrameri
800 900 1000 1100700 (m/z)
20
60
100
709
737 765 793821
849879
907 935 963991 1021 1049107711051133
Pentameri
Esameri
Eptameri
x 4
% In
tens
ità%
Inte
nsità
R CH CH CO CH
R
O CH2 CO O CH
R
CH2 COOH[ ]n
Heating mechanisms heat exchange Heating with Microwave
Benefits :� Energy saving� Process Efficiency� Restrictions on the use of halogenated
solvents
Design For Efficient Energy : Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperature and pressure.
What are the microwave
The microwaves are not ionizing electromagnetic waves having a wavelength between 1 mm ( ν = 300 GHz) and 1 m ( ν = 300 MHz), they are located in the area of the spectrum between t he frequencies of the infrared and the radio waves.The frequency of 2.45 (± 0.05) GHz, corresponding in vac uum at a wavelength ( λ) of 12.2 cm, is that used for applications in the domestic field, scientific, medical, and for many i ndustrial processes.
Chemical synthesis of copolyesters.
1. PTSA·H2O, Chloroform, Toluene (reflux)
2. Azeotropic (dehydration)
+
PCL m
O CH2 CH2 CH
2CH2 C
O
CH2PHB n
O CH CH2
C
OCH3
n
O CH CH2
C
OCH3
m
O CH 2 CH2
CH 2 CH 2 CH2
C
O
P(HB-co-CL)
A 54/46 15 7.8 1,41 0,16 0,3 1/2
B 45/55 23 n.d. n.d. 0,21 0,52 2/2
C 75/25 19 n.d. n.d. 0,42 0,92 3/2
E 55/45 52 5.2 1,3 0,1 0,21 1/2
F 48/52 49 6.4 1,27 0,12 0,25 2/2
G 55/45 30 9 1,2 0,17 0,36 3/2
Sample HB/CL a Yield (%) Mw·10 3 b Mw/Mn c DT d DR e RT(h) f
Conventionalheating
D 55/45 10 7.9 1,3 0,37 0,74 5/2
Microwaveheating
H 46/54 26 12 1,24 0,31 0,63 5/2
Table 8. Transesterification Conditions, Yields, MolecularWeights, and Degree of Transesterification of P(HB -co-CL) Copolymers.
aMolar composition of the resulting copolymers. b Weight-average molecular weight. c Molecular weight distribution. d Degree of transesterification at the end of the secondstage of the reaction. e Degree of randomness at the end of the second stage of th e reaction. f Duration in hours of the two transesterification stages. n.d.: not detemined.
b df he g l
a
cn
O CH CH2
C
OCH3
m
O CH2 CH2 CH2 CH2 CH
2C
O
i
a
b
c
e g
i
f+h
(ppm)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5
200 MHz 1H-NMR spectra of the copolymer P(HB– co-45%mol CL) (sample D) obtained with conventional heating.
n’
m+m’
a
bc
e
g
i
f+h
n+n’
(ppm)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5
nCH
3
H
H H
H
a
b c dn
O CH CH2
C
OCH3
f he g l m
O CH2
CH2CH
2 CH2CH2
C
O
i
S
O
O
m’
nm
200 MHz 1H-NMR spectra of the copolymer P(HB– co-54%mol CL) (sample H) obtained with microwave heating.
n’
ab
c
d
e
f g
hi
l
(ppm)
0102030405060708090110120130140150160170180 100
b df he g l
a
cn
O CH CH2
C
OCH3
m
O CH2 CH2 CH2 CH2 CH
2C
O
i
50 MHz 13C-NMR spectra of the copolymer P(HB– co-45%mol CL) (sample D) obtained with conventional heating.
ab
c
d
e fi
l
gh
m+m’ n+n’
(ppm)0102030405060708090100110120130140150160170180
CH3
H
H H
H
a
b c dn
O CH CH2
C
OCH3
f he g l m
O CH2
CH2CH
2 CH2CH2
C
O
i
S
O
O
m’ n’
nm
50 MHz 13C-NMR spectra of the copolymer P(HB– co-54%mol CL) (sample H) obtained with microwave heating.
CCC
BCC
BCB
CCB CBC
BBBCBB
168.5169.0169.5170.0170.5171.0171.5172.0172.5173.0173.5174.0174.5
BBC
(ppm)
13C-NMR spectral expansion of the carbonyl region of the copo lymer(sample H).
)(
2
CBBC
BB
II
XL
+=
)(
2
CBBC
CC
II
XL
+=
where XB and XC are the dyad mole fractions of HB and CL calculable by the equations:
)(21
CBBCBBB IIIX ++= )(21
CBBCCCC IIIX ++=
CBBC IIDT += CB LLDR 11 +=
For a random copolymer of 1:1 composition, these paramet ers are expectedto assume the values LB = LC = 2, DT = 0.5 and DR = 1.
200
400
600
800
1000
4500 5000 5500 6000 6500 7000 7500
(m/z)
5750 5850 5950 (m/z)
57
54
57
82
58
10
58
38
58
66
58
94
59
22
59
50
: Spettro MALDI-TOF della frazione eluita dopo il massimo del tracciato GPC del copolimero P(HB-co- 45 mol%CL) (campione D).
MALDI-TOF mass spectrum of the fraction eluting after the maximumof the GPC trace of the copolimer P(HB- co- 45 mol%CL) (sample D).
: Spettro MALDI-TOF della frazione eluita dopo il massimo del tracciato GPC del copolimero P(HB-co- 45 mol%CL) (campione D).
1. PTSA·H2O, Chloroform, Toluene (reflux)
2. Azeotropic (dehydration)
+
PCLm
O CH2
CH2 CH2
CH2CH
2C
O
P(HB-co-HV)n
O CH CH2 C
OCH3
o
CH CH2 C
O
CH3
CH2
O
Chemical synthesis of terpolyesters.
CH
P(HB-co-HV-co-CL)
m
O CH2
CH2 CH2
CH2 CH2 C
O
n
O CH CH2 C
OCH3
o
CH CH2 C
O
3
CH2
O
L 51/15/34 30 6.7 1,36 0,61 1,05 1/2
M 47/12/41 19 11.3 1,16 0,71 1,41 2/2
N 48/13/39 13 8.1 1,12 0,81 1,54 3/2
P 62/14/24 51 8.1 1,3 0,64 1,64 1/2
Q 58/15/27 37.5 9.1 1.9 0,7 1,27 2/2
R 68/13/19 35 6.7 1,2 0,75 1,47 3/2
Sample HB/HV/CL a Resa (%) Mw·103 b Mw/Mn c DT d DR e RT(h) f
Conventionalheating
Microwaveheating
aMolar composition of the resulting terpolymers. b Weight-average molecular weight. c Molecular weight distribution. d Degree of transesterification at the end of the secondstage of the reaction. e Degree of randomness at the end of the second stage of th e reaction. f Duration in hours of the two transesterification stages.
Table 9:Transesterification Conditions, Yields, MolecularWeights, and Degree of Transesterification of P(HB -co-HV-co-CL) Terpolymers.
(ppm)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0
m
g+n
c
b+dei+pa
h+o
m
CH
e n
O CH CH2
C
OCH3
o
CH CH2
C
O
CH3
CH2
O
f
g
h li
n
O CH2
CH2
CH2 2
CH2 C
O
ma b c d o p q
Spettro 1H-NMR a 200 MHz del terpolimero P(3HB-co-12%mol 3HV-co-41%mol CL) (campione M).Spettro 1H-NMR a 200 MHz del terpolimero P(3HB-co-12%mol 3HV-co-41%mol CL) (campione M).
200 MHz 1H-NMR spectra of the terpolymer P(HB- co-12%mol HV- co-41%mol CL) (sample M).
n
m
CHe
O CH CH2
C
OCH3
o
CH CH2
C
O
CH3
CH2
Of
g
h li
n
O CH2
CH2
CH2 2
CH2 C
O
ma b c d o p qCH
3
H
H H
H
S
O
O
x’ y’
yx
(ppm)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0
m
g+n
c
b+de
i+pa
h+oy+y’ x+x’
7.58.0
200 MHz 1H-NMR spectra of the terpolymer P(HB- co-15%mol HV- co-27%mol CL) (sample Q).
m
g
dc
e
n
b
p
i
a
h
o
l+q
f
(ppm)
0102030405060708090100110120130140150160170180
m
CH
e n
O CH CH2
C
OCH3
o
CH CH2
C
O
CH3
CH2
O
f
g
h li
n
O CH2
CH2
CH2 2
CH2
C
O
ma b c d o p q
50 MHz 13C-NMR of the terpolymer P(HB- co-12%mol HV- co-41%mol CL) (sample M).
H
n
m
CHe
O CH CH2
C
OCH3
o
CH CH2
C
O
CH3
CH2
Of
g
h li
n
O CH2
CH2
CH2 2
CH2
C
O
ma b c d o p qC3
H
H H
H
S
O
O
x’ y’
yx
0
(ppm)
102030405060708090100110120130140150160170
m
g
dce
n
b
p
i
a
h
o
l+q
fy+y’ x+x’
180
50 MHz 13C-NMR spectra of the terpolymer P(HB- co-15%mol HV- co-27%mol CL) (sample Q ).
CC
CV
BC
VCBC
VV
BB
(ppm)168.8169.2169.6170.0170.4170.8171.2171.6172.0172.4172.8173.2173.6
BV,VB
Espansione dello spettro 13C NMR della regione dei carbonili del terpolimero M.Espansione dello spettro 13C NMR della regione dei carbonili del terpolimero M.Espansione dello spettro 13C NMR della regione dei carbonili del terpolimero M.
13C-NMR spectral expansion of the carbonyl region of the terp olymer(sample M).
Espansione dello spettro 13C NMR della regione dei carbonili del terpolimero M.
where XB, XV, and XC are the dyad mole fractions of HB, HV and CL calculable by the equations:
)(
2
VBBVCVBCCB
B
BIIIII
XL
++++=
)(
2
VBBVCVBCCB
VV
IIIII
XL
++++=
)(
2
VBBVCVBCCB
C
CIIIII
XL
++++=
)(21
VBBVCVBCCBBBB IIIIIIX +++++= )(21
VBBVCVBCCBVVV IIIIIIX +++++=
)(21
VBBVCVBCCBCCC IIIIIIX +++++=
VCB LLLDR 111 ++= DT= ICB+IBC+ICV+IVC+IBV+IVB/2XB XC+2XCXV+2XBXV
Conclusion 1
Through bacterial fermentation were obtained for the first time PHA using very long chain fatty acids (VLCFA), more than 20 C atoms and B. carinataI oil. The PHA produced by fatty acid with odd number of carbon atoms are flexible materials whose physical characteristics do not vary significantly as a function of the side chain, although longer pendant groups confer a greater speed of recrystallization.The PHA produced by using erucic and nervonic acids, are transparent as well, partially crystalline and therefore they show rubber-like characteristics. Their proposed use is as scaffold in tissue engineering and in the pharmaceutical delivery system.The PHA from B. carinata oil is a transparent material, totally amorphous. The presence of double bonds allows the derivatization and functionalization.
By chemical synthesis were obtained biodegradable and biocompatible copolymers and terpoIymers. The structure of these polymers is random or microblock depending on the duration of the reaction or the amount of catalyst used and the type of heating used. At equal number of hours of reaction, and degree of transesterification catalyst used, the use of microwaves has allowed to obtain higher yields for both copolymers that for the terpolymers.Copolymers and terpolymers obtained by this method are capable of producing micro-and nanoparticles used in the drug delivery system.
Conclusion 2