Pectin-Based Hydrogels for Drug Delivery Applications

Pectin-Based Hydrogels for Drug Delivery Applications: History

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Subjects: Pharmacology & Pharmacy

Contributor:

Sung Soo Han

Seong Min Ji

Min Jung Park

Maduru Suneetha

Uluvangada Thammaiah Uthappa

Among the various reported biopolymer-based hydrogel drug delivery systems, pectin (Pec) is an exceptional natural polymer due to its unique functionalities and excellent properties such as biocompatibility, biodegradability, low-cost, and simple gelling capability, which has received considerable interest in the drug delivery fields.

hydrogels
pectins
controlled release
biopolymers
targeted drug delivery

1. Introduction

Biomaterials with exceptional properties have gained a lot of study interest, specifically in drug delivery applications. Polymers, both synthetic and natural, are regarded as better candidates in the fabrication of biomaterials [1,2,3,4]. Hydrogels, films, nanoparticles, and nanocomposites are just a few of the drug formulations that have been designed and advanced in drug delivery fields [5,6,7,8]. Among the formulations above-mentioned, hydrogels have grown in popularity due to their intriguing properties such as biocompatibility, biodegradability, and exclusive “soft-wet” nature in correlation to biological tissue [9,10]. It is worthwhile mentioning that hydrogels have a high-water content, which could swell and adsorb liquid due to their porous nature, and an injectable hydrogel is highly efficient for clinical use. In terms of tumor application, hydrogels possess excellent biocompatibility and controllability, and some of these hydrogel systems are used in various other applications such as additives, the chemical industry, energy, and water treatment [11,12,13,14,15,16]. Despite these exceptional benefits, hydrogels in bio-related applications face some challenges due to limitations such as mechanical stiffness, water sensitivity, and instability in physiological conditions [17].

Polymeric materials are classified into two types: synthetic and natural. Because of their biodegradability and biocompatibility, natural polymers have distinct merits over synthetic polymer systems. The main disadvantages of using natural polymers are their low mechanical properties over synthetic polymers, which makes them unsuitable for a variety of biomedical applications. Several reports have specified that the most synthetic polymers have drawbacks such as high cytotoxicity and low biocompatibility [18,19]. Generally, biopolymers are comprised of monomeric units covalently attached to form bigger biomolecules. Usually, pectic substances are differentiated into four different types: protopectin, pectic acid, pectinic acid, and Pec [20]. Among the various biopolymers, Pec is a kind of water-soluble anionic heteropolysaccharide found from the primary cell walls of terrestrial plants extracted using chemical or enzymatic process [21]. Pec possesses a higher range of heterogeneity in their structure due to their sources and methods of different extraction process [22]. Pec is considered as a promising candidate in the drug delivery field due to its excellent features such as non-toxicity, biocompatibility, biodegradability, low-cost, antibacterial, and anti-inflammatory properties [23].

2. Sources

Some of the sources for Pec are from apple pomace, citrus peels, and, more recently, sugar beet pulp [25]. Certainly, tropical and subtropical fruit by-products are primarily a significant source of Pec. Nevertheless, it is important to mention that the Pec yield and physicochemical properties of Pec are affected by the extraction technique as well as additional variables such as the extraction time, type of acid, pH, temperature, and the liquid–solid ratios [26].

3. Pectin Extraction

The yield of extracted Pec as well as the quality can be used to evaluate the suitability of the extraction method because mass transfer into the extraction solvents governs Pec extraction. To extract Pec from natural sources, several methods have been used including traditional hot extraction and advanced procedures such as ultrasound, microwave, and enzymatic processes. Huge efforts are being made to promote “green” chemistry and technology. In terms of Pec extraction, hot conventional extraction necessitates a lengthy protocol, more energy, and the use of strong acids, which is contrary to “green” chemistry principles. Thus, an outline is depicted in this section on conventional and non-conventional extraction methods.

3.1. Conventional Extraction

Extraction temperature, solid–liquid ratio, pH, particle size, and extraction time are all factors that influence the yield and quality of the extracted Pec. The utilization of mineral acids for Pec extraction is linked to environmental concerns as well as higher costs. Concerning the emergent concept of “green” chemistry and the drawbacks associated with the practice of mineral acids, the emphasis is now shifting to “food” compatible acids [27].

3.2. Ultrasound Mediated Extraction

Ultrasonic waves with frequencies from 20 to 100 kHz are commonly used. It is important to note that ultrasound frequency influences the extraction process because it influences the size of the microbubbles and their resistance to mass transfer. Furthermore, an upsurge in ultrasound frequency results is a decrease in the production and intensity of cavitation in liquid [28,29]. Several studies backing up the substantial assistance of the ultrasound-assisted extraction has several merits including low energy, less extraction time, minimal solvent, and enhanced extraction yield in support of using ultrasound as a “green” extraction method.

3.3. Microwave Mediated Extraction

This technique needs less processing time and solvent, and produces a higher extraction yield and generate superior qualities [30]. Microwave extraction is the process of applying a microwave field to a dielectric material. Ionic conduction and dipole rotation heat the solvent–sample matrix. Microwave energy initiates the electrophoretic transfer of ions and electrons, resulting in an electric field that drives particle movement, whereas dipole rotation is instigated by the substitute movement of polar molecules. Microwave power, measured in Watts (W), is a key factor in Pec extraction. Increased microwave power was found to be positively related to extraction efficiency [31].

3.4. Enzyme Aided Extraction

For enzyme-aided Pec extractions, enzymes must be able to display reactions with precise specificity and selectivity. Enzymes used in Pec extraction disturb features of the plant cell wall, enabling pectin release and reducing the complete extraction period [32]. There are more additional benefits of using enzyme aided extraction such as avoiding the corrosion of equipment by acids, reduced energy consumption, and the specificity of enzymes yield an improved quality of Pec [33].

3.5. Combination of Non-Conventional Technologies

Researchers have looked at how non-traditional extraction techniques combine to effectively extract Pec from tropical and subtropical fruit waste. Ultrasound-microwave-assisted extraction, which combines ultrasonic and microwave extraction approaches, is viewed as an efficient process [34,35]. Ultrasound-microwave-mediated extraction involves rapid yield and competent Pec extraction at low temperatures at ambient conditions, saving energy, time, and is economically viable [36].

4. Structure of Pec

Pec is widely present in the cell walls of terrestrial/earthy plants [37]. Pec was made and explored in the powder form, which is very simple to use and handle [38]. Pec is recognized as a significant component of the middle lamella, which helps to keep cells organized. Every part of the plant contains different amounts of Pec and chemical assemblies. In terms of the chemical composition and molecular density, Pec in fruits and vegetables exists in poly-molecular and poly-disperse forms [39]. The monomeric units of Pec may vary depending on the sources, procedure used for separation, and successive examinations. Depending on the origin and method of isolation, diverse properties of Pec can be used to prepare its innumerable forms [40]. The Pec is comprised of chemical moieties such as the carboxylic (-COOH) group, ester and amide (-NH₂) groups [41].

5. Physical-Chemical Properties of Pec

Pec is a class of substances that when it is dissolved in water under certain environments, it can form gels. It is obtained from protopectin, which is found in the plant cell middle lamellae [43]. All of Pec’s physical properties are due to its bi-linear poly-anion configuration (poly-carboxylate) [44]. When it comes to chemical features, the depolymerization of dissolved Pec occurs in aquatic classifications, and Pec has the highest stability at pH 4. The Pec de-esterifies below and above this pH, resulting in decreased stability. Depolymerization occurs at low pH levels via the acid catalyst hydrolysis of glycosidic bonds [45].

6. Application of Pec-Based Hydrogels in Drug Delivery

Over the last 50 years, hydrogels based on biodegradable natural polymers have been widely used in drug delivery systems [47]. Hydrogels have expanded in the drug delivery field as their three-dimensional structures have exclusive properties such as being hydrophilic in nature, biocompatibility, biodegradability, moist environments in surrounding tissues, and low cost [23,48].

Overall, Table 1 summarizes the various types of Pec-based hydrogel systems, the drugs used, and their key features involved in drug delivery applications.

Table 1. Summary of various types of Pec-based hydrogel systems, drugs used and their key features.

Serial no.	Hydrogel Systems	Drugs Used	Key Features	Reference
1	LDL-Pec-Alg	CUR	Release profile of drug demonstrated with little slower rate in the simulated GI conditions, signifying role as oral drug delivery systems	[49]
2	MNP-Pec	DS	Suggesting swelling controlled diffusion mode of drug release profiles	[50]
3	SF-OP-PLLA	Vanco	Significant sustained release up to 192 h and non-toxic against hAD-MSCs	[51]
4	Pec-5-HTP	TET	Improved biocompatibility and non-toxicity are in tolerable limits	[52]
5	Pec-PEG-MAA	SZ	Drug release explicitly at colonic pH and toxicological studies revealed safe efficacy	[53]
6	Pec-CaCO₃-PEG	BSA	Encapsulation efficiency was around 98% and drug release profile was around 9 h at the colon site	[54]
7	Pec-LA-MAA	OL	Controlled inhibition against HCT-116 and MCF-7 cells	[55]
8	Pec-AG-MMT	ZIP	Slow release and effective carrier for the treatment of schizophrenia	[56]
9	Pec-TBA	THP	Additional flexible nature and controlled release of drug	[57]
10	Pec-CS-n-IO	5-FU	Remarkable injectable, self-healing and biocompatible	[58]
11	Pec-HPMC	GHBr	Intelligent response to environmental conditions and toxicity studies conducted proved with safe efficacy	[59]
12	Pec	IQ	Displayed superior adhesiveness and higher penetration of the drug inside the skin	[53]
13	Pec-ZPN	DOX	pH dependent release cytotoxicity effects against cervical cancer cell lines	[61]
14	Pec-PA	BUD	Sustained release behavior and sustained release of 1400 min	[62]
15	CNF-Alg-Pec	5-FU	Enabled in modulating breast tumor cells	[63]
16	NF-Pec-Alg	(CH)	Superior cytocompatibility	[64]
17	Pec-CS	5-FU	Cytocompatible for fibroblast L929 cells	[65]
18	Pec-Mag-CS	MTZ	Improved drug release and pH dependent	[66]
19	Pec-PNIPAAm	DOX	Good biocompatibility and biodegradability	[67]
20	Amp-Pec-FSA	FSA	Proven with less cytotoxicity	[68]
21	LMP	CUR	Inhibit premature release in GI and able to release drug in colon area	[69]
22	Pec-Alg-Zn	GS	95% of encapsulation efficiency and drug release, specifically in colon conditions	[70]
23	Prc-K-CRG	TA	Cell culture studies revealed that none of the patch formulations were toxic	[71]
24	Pec-Phe	MT	Sustained release with swelling properties	[72]
25	LMP	PRO	Improved structural integrity	[73]
26	Pec-CSNP	QR	Sustained release and cell viability above 80% on the L929 cell line	[74]
27	Pec-AH-DA	DOX	Xenograft CT-26 tumor model in mice trial aided in preventing tumor growth	[75]
28	Pec-LZH	BFN	Low release rate and biocompatible	[76]
30	Pec-CMC-CHO	LM	Inhibited the development of lung adenocarcinoma in xenograft mice	[77]
31	Pec-CNH	AS	Controlled drug release up to 60 h at different pH	[78]

This entry is adapted from the peer-reviewed paper 10.3390/gels8120834

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