**18. Surface specificity**

Cell adhesion to adsorbed proteins is achieved via integrin and other receptors in the cell membrane and the occurrence of this triggered intracellular signaling events. Thus, the control of protein adsorption on biomaterials surfaces is crucial to controlling and directing cell responses. Oligopeptides with specific binding sites have been incorporated to control cell adsorption to the protein surface and these include short oligopeptide, e.g., adhesive oligopeptide is an arginine-glycine-aspartic acid (or RGD) [73] that is found in a number of different extracellular matrix proteins, such as fibronectin [74], laminin [75], collagen [76], and vitronectin [77]. Short oligopeptides are less expensive, easy to synthesize, and has greater flexibility for surface modification compared to bulky and labile intact proteins. To a surface modified using nonfouling PEG (99%) and RGD (1%), the protein adsorption was minimal (2 ng/cm2) leaving the sufficient RGD sites for fibroblast cell adhesion [78]. Structure and conformation of oligopeptides influence modulating cell adhesion as demonstrated with the use of immobilized cyclic RGD peptide which increased human bone marrow stromal cell adhesion to that of linear RGD peptides [79] (**Table 1**).


**149**

**S/No.**

**IV** Silk disc implants Bone biomaterials implant

> **V**

**SYSTEMIC DRUG DELIVERY**

Polylactide

Cholesterol-modified

Chondrocytes

The formulation shows lower critical gelation temperature, higher mechanical

strength, larger pore size, better chondrocyte adhesion, and slower degradation

compared to plain polylactide scaffold gels. The hydrogel serves as a promising

chondrocyte carrier for cartilage tissue engineering and gives an alternative

Toxicology studies showed that both male and female rats tolerated ~10-fold

[89]

ACE2/ANG-(1–7) higher than efficacy dose. The efficient attenuation of

pulmonary arterial hypertension with no toxicity augurs well for the clinical

advancement of the first oral protein therapy to prevent/treat underlying

pathology for this disease.

solution to surgical cartilage repair

poly(ethylene

glycol)–polylactide

scaffold

hydrogel

injections

ANG-(1–7)

Lyophilized lettuce cells

Lyophilized lettuce cells

(ACE2/ANG-(1–7))

(ACE2/ANG-(1–7))

functionalized

plant

chloroplast

**VI**

**VAGINAL DRUG DELIVERY SYSTEMS**

Organogel Vaginal rings

Silicone matrix polymer

Dapivirine

Palm oil and hyaluronic

Maraviroc

There was a 2.5-fold increase in the percentage of maraviroc release in the

[90]

presence of hyaluronidase, hence the effectiveness of hyaluronidase enzyme

acting as a trigger. This shows the potential use of palm oil/hyaluronic acid-based

organogel for the vaginal delivery of anti-HIV microbicide for HIV prevention

A monthly vaginal ring containing dapivirine reduced the risk of HIV-1

[91]

infection among African women, with increased efficacy in subgroups with

evidence of increased adherence

acid

Hydroxyapatite

Doxorubicin-loaded cyclodextrin

**IMPLANT DRUG DELIVERY SYSTEMS**

Silk fibrin

IgG antibody or human immunodeficiency virus (HIV) inhibitor 5P12-RANTES

SF was formulated into insertable discs that can encapsulate either IgG antibody or human immunodeficiency virus (HIV) inhibitor 5P12-RANTES. The water vapor annealing showed a sustained release for 31 days and this released protein could inhibit HIV infection in both blood and human colorectal tissue

**Drug delivery systems**

**Biomaterial**

**API**

**Significance of the study**

**Reference**

[86]

*Biomaterials for Drug Delivery: Sources, Classification, Synthesis, Processing, and Applications*

[88]

*DOI: http://dx.doi.org/10.5772/intechopen.93368*

[87]

Hydroxyapatite-cyclodextrin-doxorubicin chemotherapeutic strategy enhanced the drug-targeting effect on tumor cells while protecting the more sensitive healthy cells after implantation. A successful integration of such a drug delivery system might allow healthy cells to initially survive during the doxorubicin exposure period


*Biomaterials for Drug Delivery: Sources, Classification, Synthesis, Processing, and Applications DOI: http://dx.doi.org/10.5772/intechopen.93368*

*Advanced Functional Materials*

[80]

**148**

**S/No.**

**Drug delivery** 

**Biomaterial**

**API**

**Significance of the study**

**Reference**

**systems**

**ORAL DRUG DELIVERY SYSTEMS**

Silk

Silk and fibrin

Celecoxib and curcumin

Silk fibroin nanoparticles were seen to promote anti-inflammatory properties

of celecoxib or curcumin and could be exploited for oral osteoarthritis

management since a controlled drug release was achieved by varying the drug

PLA nanofibers associated with metronidazole (MNZ) were used to control

[81]

microbiological proliferation during periodontitis treatment, inhibiting bacteria

growth during the treatment

loading

Nanoparticles

Electrospun

Polylactic acid

Metronidazole

fibers

**OCULAR DRUG DELIVERY SYSTEMS**

Nanocomposite

Hyaluronic acid

Latanoprost

The hyaluronic acid nanocomposite hydrogels, with controlled degradation

[82]

properties and sustained release, could serve as potential drug delivery systems

for many ocular diseases as they controlled the release of latanoprost in vitro

The drug release from the lenses was directly proportional to the amount of

[83]

drug loaded and the lenses at the different loading concentrations showed

transmittance of 95–97%. The silicone hydrogel contact lenses can be used to

control drug delivery to the eye and is an alternative ocular delivery technique in

the treatment or prevention of corneal infections

Large porous celecoxib-PLGA microparticles prepared using supercritical fluid technology exhibited sustained drug delivery and antitumor efficacy, without

[84]

causing any significant toxicity

The in vitro antibacterial studies showed that HPMC-PVP-FLU nanoparticles

[85]

displayed superior effect against Gram-positive bacteria compared to the

unprocessed FLU and positive control

hydrogel

Hydrogel

Silicone

Ofloxacin and

Chloramphenicol

contact lens

**PULMONARY DRUG DELIVERY SYSTEMS**

Porous particles

Nanoparticles

Nanopolymeric

Fluticasone

particles consisting

of hydroxyl propyl

methylcellulose

(HPMC), polyvinylpyrrolidone (PVP)

Poly(lactide-coglycolide) (PLGA)

Celecoxib


**Table 1.**

**151**

*Biomaterials for Drug Delivery: Sources, Classification, Synthesis, Processing, and Applications*

Poly (ethylene glycol) (PEG), or poly(ethylene oxide) (PEO) having nonfouling surfaces demonstrates protein and cell resistance capabilities. PEG have been attached to materials in such a manner to render them nonfouling through processes like covalent immobilization, adsorption, or interpenetration. PEG has been covalently attached to mussel adhesive protein to form a nonfouling and a sticky segment copolymer [94] with gold and titanium surfaces attached to the sticky segment, while the PEG chains occur at the new interface. It should be noted that the nonfouling ability/attribute of PEG is dependent on the surface chain density that is prone to oxidants damaged. However, the use of plasma deposition of tetra ethylene glycol dimethyl ether (tetraglyme) on PEG will reduce protein surface adsorption [95]. Other materials with nonfouling surfaces include phospholipid surfaces [96] and saccharide surfaces [97], and these biomaterials ensure increased compatibility issues between the drug carrier systems and biological

Materials which respond to environmental changes are attractive particularly in vivo as these can be utilized to control drug release, cell adhesiveness, mechanical properties, or permeability. These environmental changes can be brought about by stimulants like pH [98], temperature [99], and light [100]. The body employs changes in pH to facilitate a range of different processes. For example, along the gastrointestinal track, food is broken down into nutritive substances in the stomach under acidic pH ∼ 2 and subsequently absorbed in the small intestine (pH ∼ 7). Patient often prefers the oral drug delivery requiring routine, periodic delivery of drugs and for effectiveness, the drug must resist the stomach acidic pH. The pH-sensitive materials that are mindful of gastrointestinal tract pH variation have been developed to transport drugs successfully through the stomach to the small intestine. Such successful materials include pH responsive hydrogels prepared from poly(methacrylic acid) grafted with poly(ethylene glycol) (PMAA-g-PEG) that swells in response to pH. For instance, the gel shrinks by trapping the drug cargo pH ∼ 2 as interpolymer complexes are formed, but at physiological pH ∼ 7, the gel can swell 3–25 times based on its composition as it releases its cargo in the target site [101]. Insulin-loaded PMAA-g-PEG gels have been orally delivered to diabetic mice with a significant decrease in glucose levels as protein function is protected in acidic and digestive enzymes environments [102].

Self-organization or self-assembly is based on the formation of weak noncovalent

bonds, like hydrogen, ionic, or Van der Waals bonds or hydrophobic interactions [103]. In amphiphilic molecules, there are hydrophobic and hydrophilic segments that self-assemble to form nanometer 3D structures like micelles, vesicles, and tubules, which depend on the molecule's length and composition [104–107]. When any of these are dispersed in aqueous solvent, the hydrophobic segments agglomerate and water is expelled to produce a well-ordered structure useful in biomedical applications. Phospholipid a naturally occurring amphiphilic molecule that is largely compose of cell membrane is one such amphiphilic molecules while an oligomer, a polymer of amino acids, can be synthesized to have hydrophobic, hydrophilic, charged, etc., regions that can self-assemble into a macroscopic hydrogel [108]. The self-assembled biomaterials can be engineered for use in nanotechnology, tissue

systems to which they are introduced to elicit a pharmacological activity.

*DOI: http://dx.doi.org/10.5772/intechopen.93368*

**19. Nonfouling surfaces**

**20. Smart biomaterials**

**20.1 Self-assembled biomaterials**

engineering for drug and cell carriers.

*Drug delivery systems showing the significance of the biomaterials utilized in delivering active pharmaceutical ingredients at their biological target site.* *Biomaterials for Drug Delivery: Sources, Classification, Synthesis, Processing, and Applications DOI: http://dx.doi.org/10.5772/intechopen.93368*
